The Radiopharmaceutical Science of Monoclonal Antibodies and Peptides for Imaging and Targeted in situ Radiotherapy of Malignancies

Handbook of Pharmaceutical Biotechnology

Volumn , Issue , 2006, Pages 883-942

  Reilly, Raymond M ^a  

^a UNIVERSITY OF TORONTO   (Canada)

Author keywords

Radioimmunotherapy (RIT) or peptide directed radiotherapy (PDRT); Radiolabeled MABS and peptides; Radiopharmaceutical science

Indexed keywords

EID: 61649124686     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9780470117118.ch06g     Document Type: Chapter

References (265)

1. Ferlay J, Bray F, Pisani P, et al. (2000). Cancer incidence, prevalence and mortality worldwide. IARC CancerBase, 5th ed: IARC Press, Lyon, France.
2. Reilly R M (2005). Biomolecules as targeting vehicles for in situ radiotherapy of malignancies. In J Knaeblein, R Mueller, (eds.), Modern Biopharmaceuticals: Design, Development and Optimization. Wiley-VCH, Weinheim, Germany, pp. 497-526.
3. Goldenberg D M (1989). Future role of radiolabeled monoclonal antibodies in oncological diagnosis and therapy. Semin. Nucl. Med. 19(4):332-339.
4. Baselga J (2001). Clinical trials of Herceptin (trastuzumab). Eur. J. Cancer. 37:S18-S24.
5. Behr T M, Béhé M, Wörmann B (2001). Trastuzumab and breast cancer. N. Engl. J. Med. 345:995-996.
6. Krenning E P, Kwekkeboom D J, Bakker W H, et al. (1993). Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123I-Tyr3]-octreotide: The Rotterdam experience with more than 1000 patients. Eur. J. Nucl. Med. 20:716-731.
7. Reilly R M, Sandhu J, varez-Diez T M, et al. (1995). Problems of delivery of monoclonal antibodies. Pharmaceutical and pharmacokinetic solutions. Clin. Pharmacokinet. 28(2):126-142.
8. Yokota T, Milenic D E, Whitlow M, et al. (1992). Rapid tumor penetration of a singlechain Fv and comparison with other immunoglobulin forms. Cancer Res. 52(12):3402-3408.
9. Saga T, Neumann R D, Heya T, et al. (1995). Targeting cancer micrometastases with monoclonal antibodies: a binding-site barrier. Proc. Natl. Acad. Sci. USA. 92(19):8999-9003.
10. van Osdol W, Fujimori K, Weinstein J N (1991). An analysis of monoclonal antibody distribution in microscopic tumor nodules: consequences of a "binding-site barrier". Cancer Res. 51:4776-4784.
11. Behr T M, Goldenberg D M, Becker W (1998). Reducing the renal uptake of radiolabeled antibody fragments and peptides for diagnosis and therapy: Present status, future prospects and limitations. Eur. J. Nucl. Med. 25:201-212.
12. Jamar F, Barone R, Mathieu I, et al. (2003). 86Y-DOTA0-D-Phe1-Tyr3-octreotide (SMT487)- a phase 1 clinical study: pharmacokinetics, biodistribution and renal pro tective effect of different regimens of amino acid co-infusion. Eur. J. Nucl. Med. 30:510-518.
13. Pagani M, Stone-Elander S, Larsson S A (1997). Alternative positron emission tomography with non-conventional positron emitters: effects of their physical properties on image quality and potential clinical applications. Eur. J. Nucl. Med. 24:1301-1327.
14. Xue L Y, Butler N J, Makrigiorgos G M, Adelstein S J, Kassis A I (2002). Bystander effect produced by radiolabeled tumor cells in vivo. J. Nucl. Med. 43(Suppl):276P-277P.
15. Finn R, Cheung N-KV, Divgi C, et al. (1991). Technical challenges associated with the radiolabeling of monoclonal antibodies utilizing short-lived, positron emitting radionuclides. Nucl. Med. Biol. 18:9-13.
16. Hunter W M, Greenwood F C (1962). Preparation of 131I labeled human growth hormone of high specific activity. Nature. 194:495-496.
17. Fraker P J, Speck J C, Jr (1978). Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem. Biophys. Res. Commun. 80(4):849-857.
18. Reilly R M, Kiarash R, Sandhu J, et al. (2000). A comparison of EGF and MAb 528 labeled with 111In for imaging human breast cancer. J. Nucl. Med. 41(5):903-911.
19. Zalutsky M R, Narula A S (1987). A method for the radiohalogenation of proteins resulting in decreased thyroid uptake of radioiodine. Appl. Radiat. Isot. 38:1051-1055.
20. Zalutsky M R, Narula A S (1988). Radiohalogenation of a monoclonal antibody using an N-succinimidyl 3-(tri-n-butylstannyl) benzoate intermediate. Cancer Res. 48:1446-1450.
21. Zalutsky M R, Noska M A, Colapinto E V, et al. (1989). Enhanced tumor localization and in vivo stability of a monoclonal antibody radioiodinated using N-succinimidyl 3-(tri-n-butylstannyl) benzoate. Cancer Res. 49:5543-5549.
22. Garg S, Garg P K, Zalutsky M R (1991). N-succinimidyl 5-(trialkylstannyl)-3- pyridinecarboxylates: A new class of reagents for protein radioiodination. Bioconjug. Chem. 2:50-58.
23. Reist C J, Garg P K, Alston K L, et al. (1996). Radioiodination of internalizing monoclonal antibodies using N-succinimidyl 5-iodo-3-pyridinecarboxylate. Cancer Res. 56:4970-4977.
24. Reist C J, Archer G E, Wikstrand C J, et al. (1997). Improved targeting of an antiepidermal growth factor receptor variant III monoclonal antibody in tumor xenografts after labeling using N-succinimidyl 5-iodo-3-pyridinecarboxylate. Cancer Res. 57:1510-1515.
25. Garg P K, Alston K L, Welsh P C, et al. (1996). Enhanced binding and inertness to dehalogenation of α-melanotropic peptides labeled using N-succinimidyl 3- iodobenzoate. Bioconjug. Chem. 7:233-239.
26. Vaidyanathan G, Affleck D J, Li J, et al. (2001). A polar substituent-containing acylation agent for the radioiodination of internalizing monoclonal antibodies: N-succinimidyl 4-guanidinomethyl-3-[131I]iodobenzoate ([131I]SGMIB). Biocon-jug. Chem. 12:428-438.
27. Vaidyanathan G, Affleck D J, Bigner D D, et al. (2002). Improved xenograft targeting of tumor-specific anti-epidermal growth factor receptor variant III antibody labeled using N-succinimidyl 4-guanidinomethyl-3-iodobenzoate. Nucl. Med. Biol. 29:1-11.
28. Shankar S, Vaidyanathan G, Affleck D, et al. (2003). N-succinimidyl 3-[131I]iodo-4- phosphonomethylbenzoate ([131I]SIPMB), a negatively charged substituent-bearing acylation agent for the radioiodination of peptides and mAbs. Bioconjug. Chem. 14:331-341.
29. Govindan S V, Mattes M J, Stein R, et al. (1999). Labeling of monoclonal antibodies with diethylenetriaminepentaacetic acid-appended radioiodinated peptides containing D-amino acids. Bioconjug. Chem. 10:231-240.
30. Franano F N, Edwards W B, Welch M J, et al. (1994). Metabolism of receptor targeted 111In-DTPA-glycoproteins: Identification of 111In-DTPA-ε-lysine as the primary metabolic and excretory product. Nucl. Med. Biol. 21:1023-1034.
31. Dumas P, Maziere B, Autissier N, et al. (1973). Specificite de L'iodotyrosine desiodase des microsomes thyroidiens et hepatiques. Biochim. Biophys. Acta. 293:36-47.
32. Stein R, Govindan S V, Mattes M J, et al. (2003). Improved iodine radiolabels for monoclonal antibody therapy. Cancer Res. 63:111-118.
33. Govindan S V, Griffiths G L, Stein R, et al. (2005). Clinical-scale radiolabeling of a humanized anticarcinoembryonic antigen monoclonal antibody, hMN-14, with residualizing 131I for use in radioimmunotherapy. J. Nucl. Med. 46:153-159.
34. Foulon C F, Reist C J, Bigner D D, et al. (2000). Radioiodinatin via D-amino acid peptide enhances cellular retention and tumor xenograft targeting of an internalizing anti-epidermal growth factor receptor variant III monoclonal antibody. Cancer Res.60:4453-4460.
35. Thorpe S E, Baynes J W, Chroneos Z C (1993). The design and application of residualizing labels for studies of protein catabolism. FASEB. 7:399-405.
36. Stein R, Goldenberg D M, Thorpe S R, et al. (1995). Effects of radiolabeling monoclonal antibodies with a residualizing iodine radiolabel in the accretion of radioisotope in tumors. Cancer Res. 55:3132-3139.
37. Reist C J, Archer G E, Kurpad S N, et al. (1995). Tumor-specific anti-epidermal growth factor receptor variant III monoclonal antibodies: use of the tyraminecellobiose radioiodination method enhances cellular retention and uptake in tumor xenografts. Cancer Res. 55:4375-4382.
38. Zalutsky M R, Xu F J, Yu Y, et al. (1999). Radioiodinated antibody targeting of the HER-2/neu oncoprotein: Effects of labeling method on cellular processing and tissue distribution. Nucl. Med. Biol. 26:781-790.
39. Sundberg Ä L, Blomquist E, Carlsson J, et al. (2003). Cellular retention of radioactivity and increased radiation dose. Model experiments with EGF-dextran. Nucl. Med. Biol. 30:303-315.
40. Townsend D W, Carney J P J, Yap J T, et al. (2004). PET/CT today and tomorrow. J. Nucl. Med. 45(suppl.):4S-14S.
41. Chatziionnou A F (2002). Molecular imaging of small animals with dedicated PET tomographs. Eur. J. Nucl. Med. 29:98-114.
42. Gambhir S S, Czernin J, et al. (2001). A tabulated summary of the FDG PET literature. J. Nucl. Med. 42(suppl.):1S-93S.
43. Bakir M A, Eccles S A, Babich J W, et al. (1992). c-erbB2 Protein overexpression in breast cancer as a target for PET using iodine-124-labeled monoclonal antibodies. J. Nucl. Med. 33:2154-2160.
44. Larson S M, Pentlow K S, Volkow N D, et al. (1992). PET scanning of iodine-124-3F9 as an approach to tumor dosimetry during treatment planning for radioimmunotherapy in a child with neuroblastoma. J. Nucl. Med. 33:2020-2023.
45. Lee F T, Hall C, Rigopoulos A, et al. (2001). Immuno-PET of human colon xenograftbearing BALB/c nude mice using 124I-CDR-grafted humanized A33 monoclonal antibody. J. Nucl. Med. 42:764-769.
46. Verel I, Visser G W M, Vosjan M J W D, et al. (2004). High-quality 124I-labelled monoclonal antibodies for use as PET scouting agents prior to 131I-radioimmunotherapy. Eur. J. Nucl. Med. Mol. Imaging. 31:1645-1652.
47. Robinson M K, Doss M, Shaller C, et al. (2005). Quantitative immuno-positron emission tomography imaging of HER2-positive tumor xenografts with an iodine-124 labeled anti-HER2 diabody. Cancer Res. 65:1471-1478.
48. Sundaresan G, Yazaki P J, Shively J E, et al. (2003). 124I-labeled engineered anti-CEA minibodies and diabodies allow high-contrast, antigen-specific small-animal PET imaging of xenografts in athymic mice. J. Nucl. Med. 44:1962-1969.
49. Iozzo P, Osman S, Glaser M, et al. (2002). In vivo imaging of insulin receptors by PET: preclinical evaluation of iodine-125 and iodine-124 labelled human insulin. Nucl. Med. Biol. 29:73-82.
50. Eary J F (2001). PET imaging for planning cancer therapy. J. Nucl. Med. 42:770-771.
51. Tolmachev V, Lovqvist A, Einarsson L, et al. (1998). Production of 76Br by a lowenergy cyclotron. Appl. Radiat. Isot. 49:1537-1540.
52. Lovqvist A, Sundin A, Ahlstrom H, et al. (1995). 76Br-labeled monoclonal anti-CEA antibodies for radioimmuno positron emission tomography. Nucl. Med. Biol. 22:125-131.
53. Sundin J, Tolmachev V, Koziorowski J, et al. (1999). High yield direct 76Br-bromination of monoclonal antibodies using chloramine-T. Nucl. Med. Biol. 26:923-929.
54. Lovqvist A, Sundin A, Roberto A, et al. (1997). Comparative PET imaging of experimental tumors with bromine-76-labeled antibodies, fluorine-18-fluorodeoxyglucose and carbon-11-methionine. J. Nucl. Med. 38:1029-1035.
55. Lovqvist A, Sundin A, Ahlstrom H, et al. (1997). Pharmacokinetics and experimental PET imaging of a bromine-76-labeled monoclonal anti-CEA antibody. J. Nucl. Med. 38:395-401.
56. Hoglund J, Tolmachev V, Orlova A, et al. (2000). Optimized indirect 76Br-bromination of antibodies using N-succinimidyl para-[76Br]bromobenzoate for radioimmuno PET. Nucl. Med. Biol. 27:837-843.
57. Wilbur D S, Hylarides M D (1991). Radiolabeling of a monoclonal antibody with Nsuccinimidyl para-[77Br]bromobenzoate. Nucl. Med. Biol. 18:363-365.
58. Mume E, Orlova A, Malmström P-U, et al. (2005). Radiobromination of humanized anti-HER2 monoclonal antibody trastuzumab using N-succinimidyl 5-bromo-3- pyridinecarboxylate, a potential label for immunoPET. Nucl. Med. Biol. 32:613-622.
59. Mume E, Orlova A, Larsson B, et al. (2005). Evaluation of ((4-hydroxyphenyl)ethyl) maleimide for site-specific radiobromination of anti-HER2 affibody. Bioconjug. Chem. 16:1547-1555.
60. Steffen A-C, Wikman M, Tolmachev V, et al. (2005). In vitro characterization of a bivalent anti-HER-2 affibody with potential for radionuclide based diagnostics. Cancer Biother. Radiopharm. 20:239-248.
61. Bruskin A, Sivaev I, Persson M, et al. (2004). Radiobromination of monoclonal antibody using potassium [76Br] (4 isothiocyanatobenzyl-ammonio)-bromo-decahydrocloso- dodecaborate (bromo-DABI). Nucl. Med. Biol. 31:205-211.
62. Winberg K J, Persson M, Malmström P-U, et al. (2004). Radiobromination of anti-HER2/neu/ErbB-2 monoclonal antibody using the p-isothiocyanatobenzene derivative of the [76Br]undecahydro-bromo-7,8-dicarba-nido-undecaborate(1-) ion. Nucl. Med. Biol. 31:425-433.
63. Okarvi S M (2001). Recent progress in fluorine-18 labelled peptide radio pharmaceuticals. Eur. J. Nucl. Med. 28:929-938.
64. Garg P K, Garg S, Zalutsky M R (1991). Fluorine-18 labeling of monoclonal antibodies and fragments with preservation of immunoreactivity. Bioconjug. Chem. 2:44-49.
65. Garg P K, Garg S, Bigner D D, et al. (1992). Localization of fluorine-18-labeled Mel-14 monoclonal antibody F(ab′)2 fragment in a subcutaneous xenograft model. Cancer Res. 52:5054-5060.
66. Page R L, Garg P K, Garg S, et al. (1994). PET imaging of osteosarcoma in dogs using a fluorine-18-labeled monoclonal antibody Fab fragment. J. Nucl. Med. 35:1506-1513.
67. Lang L, Eckelman W C (1994). One-step synthesis of 18F labeled [18F]-N-succinimidyl 4-(fluoromethyl) benzoate for protein labeling. Appl. Radiat. Isot. 45:1155-1163.
68. Vaidyanathan G, Zalutsky M R (1994). Improved synthesis of N-succinimidyl 4-[18F]fluorobenzoate and its application to the labeling of a monoclonal antibody fragment. Bioconjug. Chem. 5:352-356.
69. Page R L, Garg P K, Vaidyanathan G, et al. (1994). Preclinical evaluation and PET imaging of 18F-labeled Mel-14 F(ab′)2 fragment in normal dogs. Nucl. Med. Biol. 21:911-919.
70. Vaidyanathan G, Zalutsky M R (1997). Fluorine-18-labeled [Nle4,D-Phe7]-α-MSH, an a-melanocyte stimulating hormone analogue. Nucl. Med. Biol. 24:171-178.
71. Guhlke S, Coenen H H, Stocklin G (1994). Fluoroacylation agents based on small n.c.a. [18F]fluorocarboxylic acids. Appl. Radiat. Isot. 45:715-727.
72. Guhlke S, Wester H-J, Bruns C, et al. (1994). (2-[18F]fluoropropionyl-(D)phe1)- octreotide, a potential radiopharmaceutical for quantitative somatostatin receptor imaging with PET: synthesis, radiolabeling, in vitro validation and biodistribution in mice. Nucl. Med. Biol. 21:819-825.
73. Poethko T, Schottelius M, Thumshirn G, et al. (2004). Two-step methodology for high-yield routine radiohalogenation of peptides: 18F-labeled RGD and octreotide analogs. J. Nucl. Med. 45:892-902.
74. Wester H-J, Brockman J, Rosch F, et al. (1997). PET-pharmacokinetics of 18Foctreotide:A comparison with 67Ga-DFO- and 86Y-DTPA-octreotide. Nucl. Med. Biol. 24:275-286.
75. Chen X, Park R, Shahinian A H, et al. (2004). 18F-labeled RGD peptide: initial evaluation for imaging brain tumor angiogenesis. Nucl. Med. Biol. 31:179-189.
76. Haubner R, Kuhnast B, Mang C, et al. (2004). [18F]galacto-RGD: Synthesis, radiolabeling, metabolic stability, and radiation dose estimates. Bioconjug. Chem. 15:61-69.
77. Wester H-J, Hamacher K, Stocklin G (1996). A comparative study of n.c.a. fluorine-18 labeling of proteins via acylation and photochemical conjugation. Nucl. Med. Biol. 23:365-372.
78. Chang Y S, Jeong J M, Lee Y-S, et al. (2005). Preparation of 18F-human serum albumin: A simple and efficient protein labeling method with 18F using a hydrazoneformation method. Bioconjug. Chem. 16:1329-1333.
79. Couturier O, Supiot S, Degraef-Mougin M, et al. (2005). Cancer radioimmunotherapy with alpha-emitting nuclides. Eur. J. Nucl. Med. Mol. Imaging. 32:601-614.
80. Visser G W M, Diemer E L, Kaspersen F M (1981). The nature of the astatine-protein bond. Int. J. Appl. Radiat. Isot. 32:905-912.
81. Aaij C, Tschroots W R J M, Lindner L, et al. (1975). The preparation of astatine labelled proteins. Int. J. Appl. Radiat. Isot. 26:25-30.
82. Vaughan A T M, Fremlin J H (1978). The preparation of astatine labelled proteins using an electrophilic reaction. Int. J. Nucl. Med. Biol. 5:229-230.
83. Zalutsky M R, Narula A S (1988). Astatination of proteins using an N-succinimidyl tri-n-butylstannyl benzoate intermediate. Appl. Radiat. Isot. 39:227-232.
84. Zalutsky M R, Garg P K, Friedman H S, et al. (1989). Labeling monoclonal antibodies and F(ab′)2 fragments with the α-particle-emitting nuclide astatine-211: Preservation of immunoreactivity and in vivo localizing capacity. Proc. Natl. Acad. Sci. USA. 86:7149-7153.
85. Garg P K, Harrison C L, Zalutsky M R (1990). Comparative tissue distribution in mice of the alpha-emitter 211At and 131I as labels of a monoclonal antibody and F(ab′)2 fragment. Cancer Res. 50:3514-3520.
86. Wilbur D S, Vessella R L, Stray J E, et al. (1993). Preparation and evaluation of para-[211At]astatobenzoyl labeled anti-renal cell carcinoma antibody A6H F(ab′)2. In vivo distribution comparison with para-[125I]iodobenzoyl labeled A6H F(ab′)2. Nucl. Med. Biol. 20:917-927.
87. Zalutsky M R, Zhai X-C, Alston K L, et al. (2001). High-level production of α- particle-emitting 211At and preparation of 211At-labeled antibodies for clinical use. J. Nucl. Med. 42:1508-1515.
88. Pozzi O R, Zalutsky M R (2005). Radiopharmaceutical chemistry of targeted radiotherapeutics, Part I: Effects of solvent on the degradation of radiohalogenation precursors by 211At α-particles. J. Nucl. Med. 46:700-706.
89. Pozzi O R, Zalutsky M R (2005). Radiopharmaceutical chemistry of targeted radiotherapeutics, Part 2: Radiolytic effects of 211At α-particles influence N-succinimidyl 3-211At-astatobenzoate synthesis. J. Nucl. Med. 46:1393-1400.
90. Reist C J, Foulon C F, Alston K, et al. (1999). Astatine-211 labeling of internalizing anti-EGFRvIII monoclonal antibody using N-succinimidyl 5-[211At]astato-3pyridinecarboxylate. Nucl. Med. Biol. 26:405-411.
91. Vaidyanathan G, Affleck D, Welsh P, et al. (2000). Radioiodination and astatination of octreotide by conjugation labeling. Nucl. Med. Biol. 27:329-337.
92. Aurlien E, Larsen R H, Bruland O S (2000). Demonstration of highly specific toxicity of the α-emitting radioimmunoconjugate 211At-rituximab against non-Hodgkin's lymphoma cells. Br. J. Cancer. 83:1375-1379.
93. Liu S, Edwards D S, Barrett J A (1997). 99mTc labeling of highly potent small peptides. Bioconjug. Chem. 8:621-636.
94. Reilly R M (1993). Immunoscintigraphy of tumors using 99Tcm-labelled monoclonal antibodies: A review. Nucl. Med. Commun. 14(5):347-359.
95. Schwartz A, Steinstrasser A (1987). A novel approach to Tc-99m labeled monoclonal antibodies. J. Nucl. Med. 28:721.
96. Mather S J, Ellison D (1990). Reduction-mediated technetium-99m labeling of monoclonal antibodies. J. Nucl. Med. 31:692-697.
97. Stopar T G, Milinaric-Rascan I, Fettich J, et al. (2006). 99mTc-rituximab radiolabelled by photoactivation: a new non-Hodgkin's lymphoma imaging agent. Eur. J. Nucl. Med. Mol. Imaging. 33:53-59.
98. Stalteri M A, Mather S J (1996). Technetium-99m labelling of the anti-tumor antibody PR1A3 by photoactivation. Eur. J. Nucl. Med. 23:178-187.
99. Morales A A, Nunez-Gandolff G, Perez N P, et al. (1999). Freeze-dried formulation for direct 99mTc-labeling ior-egr/r3 mab: Additives, biodistribution, and stability. Nucl. Med. Biol. 26:717-723.
100. Ellman G L (1958). A colorimetric method for determining low concentrations of mercaptans. Arch. Biochem. Biophys. 74:443-450.
101. Iznaga-Escobar N, Morales A, Nunez G (1996). Micromethod for quantification of SH groups generated after reduction of monoclonal antibodies. Nucl. Med. Biol. 23:641-644.
102. Marks A, Ballinger J R, Reilly R M, et al. (1995). A novel anti-seminoma monoclonal antibody (M2A) labelled with technetium-99m: Potential application for radioimmunoscintigraphy. Br. J. Urol. 75(2):225-229.
103. Steffens M G, Oosterwijk E, Kranenborg M H G C, et al. (1999). In vivo and in vitro characterizations of three 99mTc-labeled monoclonal antibody G250 preparations. J. Nucl. Med. 40:829-836.
104. Vallis K A, Reilly R M, Chen P, et al. (2002). A phase I study of 99mTc-hR3 (DiaCIM), a humanized immunoconjugate directed towards the epidermal growth factor receptor. Nucl. Med. Commun. 23(12):1155-1164.
105. Torres L A, Perera A, Batista J F, et al. (2005). Phase I/II clinical trial of the humanized anti-EGF-r monoclonal antibody h-R3 labelled with 99mTc in patients with tumor of epithelial origin. Nucl. Med. Commun. 26:1049-1057.
106. Fichna J, Janecka A (2003). Synthesis of target-specific radiolabeled peptides for diagnostic imaging. Bioconjug. Chem. 14:3-17.
107. Abrams M J, Juweid M, tenKate C I, et al. (1990). Technetium-99m-human polyclonal IgG radiolabeled via the hydrazino nicotinamide derivative for imaging focal sites of infection in rats. J. Nucl. Med. 31(12):2022-2028.
108. Tang Y, Scollard D, Chen P, et al. (2005). Imaging of HER2/neu expression in BT-474 human breast cancer xenografts in athymic mice using [99mTc]-HYNIC-trastuzumab (Herceptin) Fab fragments. Nucl. Med. Commun. 26(5):427-432.
109. Ono M, Arano Y, Mukai T, et al. (2001). Plasma protein binding of 99mTc-labeled hydrazino nicotinamide derivatized polypeptides and peptides. Nucl. Med. Biol. 28(2):155-164.
110. Ultee M E, Bridger G J, Abrams M J, et al. (1997). Tumor imaging with technetium-99m-labeled hydrazinenicotinamide-Fab′ conjugates. J. Nucl. Med. 38:133-138.
111. Bangard M, Behe M, Guhike S, et al. (2000). Detection of somatostatin receptorpositive tumors using the new 99mTc-tricine-HYNIC-D-Phe1-Tyr3-octrotide: First results in patients and comparison with 111In-DTPA-D-Phe1-octreotide. Eur. J. Nucl. Med. 27:628-637.
112. Decristoforo C, Mather S J, Cholewinski W, et al. (2000). 99mTc-EDDA/HYNIC-TOC:A new 99mTc-labelled radiopharmaceutical for imaging somatostatin receptor-positive tumors: First clinical results and intra-patient comparison with 111In-labelled octreotide derivatives. Eur. J. Nucl. Med. 27:1318-1325.
113. Decristoforo C, Melendez-Alafort L, Sosabowski J K, et al. (2000). 99mTc-HYNIC-[Tyr3]-octrotide for imaging somatostatin-receptor-positive tumors: Preclinical evaluation and comparison with 111In-octreotide. J. Nucl. Med. 41:1114-1119.
114. Cornelissen B, Kersemans V, Burvenich I, et al. (2005). Synthesis, biodistribution and effects of farnesyltransferase inhibitor therapy on tumur uptake in mice of 99mTc labelled epidermal growth factor. Nucl. Med. Commun. 26:147-153.
115. Babich J W, Fischman A J (1995). Effect of "co-ligand" on the biodistribution of 99mTclabeled hydrazino nicotinic acid derivatized chemotactic peptides. Nucl. Med. Biol. 22:25-30.
116. Decristoforo C, Mather S J (1999). Technetium-99m somatostatin analogues: Effect of labelling methods and peptide sequence. Eur. J. Nucl. Med. 26:869-876.
117. Decristoforo C, Mather S J (1999). 99m-Technetium-labelled peptide-HYNIC conjugates:Effects of lipophilicity and stability on biodistribution. Nucl. Med. Biol. 26:389-396.
118. Decristoforo C, Cholewinski W, Donnemiller E, et al. (2000). Detection of somatostatin receptor-positive tumors using the new 99mTc-tricine-HYNIC-D-Phe1-Tyr3-octreotide:first results in patients and comparison with 111In-DTPA-D-Phe1-octreotide. Eur. J. Nucl. Med. 27:1580.
119. Ono M, Arano Y, Mukai T, et al. (2001). 99mTc-HYNIC-derivatized ternary ligand complexes for 99mTc-labeled polypeptides with low in vivo protein binding. Nucl. Med. Biol. 28(3):215-224.
120. Tang Y, Wang J, Scollard D A, et al. (2005). Imaging of HER2/neu-positive BT-474 human breast cancer xenografts in athymic mice using 111In-trastuzumab (Herceptin) Fab fragments. Nucl. Med. Biol. 32(1):51-58.
121. Sattelberger A P, Atcher R W (1999). Nuclear medicine finds the right chemistry. Nat. Biotechnol. 17:849-850.
122. Waibel R, Alberto R, Willuda J, et al. (1999). Stable one-step technetium-99m labeling of His-tagged recombinant proteins with a novel Tc(I)-carbonyl complex. Nat. Biotechnol. 17:897-901.
123. Schibi R, Schwarzbach R, Alberto R, et al. (2002). Steps toward high specific activity labeling of biomolecules for therapeutic application: Preparation of precursor [Re-188(H2O)(3)(CO)(3)](+) and synthesis of tailor-made bifunctional ligand systems. Bioconjug. Chem. 13:750-756.
124. Blok D, Feitsman H I J, Kooy Y M C, et al. (2004). New chelation strategy allows for quick and clean 99mTc-labeling of synthetic peptides. Nucl. Med. Biol. 31:815-820.
125. Fritzberg A R, Abrams P G, Beamier P L, et al. (1988). Specific and stable labeling of antibodies with technetium-99m with a diamide diothiolate chelating agent. Proc. Natl. Acad. Sci. USA. 85:4025-4029.
126. Rogers B E, Parry J J, Andrews R, et al. (2005). MicroPET imaging of gene transfer with a somatostatin receptor-based reporter gene and 94mTc-demotate. J. Nucl. Med. 46:1889-1897.
127. Griffiths G L, Goldenberg D M, Jones A L, et al. (1992). Radiolabeling of monoclonal antibodies and fragments with technetium and rhenium. Bioconjug. Chem. 3(91):99.
128. Griffiths G L, Goldenberg D M, Knapp Jr. F F, et al. (1991). Direct radiolabeling of monoclonal antibodies with generator-produced rhenium-188 for radioimmunotherapy:Labeling and animal biodistribution studies. Cancer Res. 51:4594-4602.
129. Iznaga-Escobar N (2001). Direct radiolabeling of monoclonal antibodies with rhenium-188 for radioimmunotherapy of solid tumors-a review of radiolabeling characteristics, quality control and in vitro stability studies. Appl. Radiat. Isot. 54:399-406.
130. John E, Thakur M L, DeFulvio J, et al. (1993). Rhenium-186-labeled monoclonal antibodies for radioimmunotherapy: preparation and evaluation. J. Nucl. Med. 34:260-267.
131. Rhodes B A, Lambert C R, Marek M J, et al. (1996). Re-188 labelled antibodies. Appl. Radiat. Isot. 47:7-14.
132. Reilly R M, Ng K, Polihronis J, et al. (1994). Immunoscintigraphy of human colon cancer xenografts in nude mice using a second-generation TAG-72 monoclonal antibody labelled with 99Tcm. Nucl. Med. Commun. 15(5):379-387.
133. Ferro Flores G, Torres-Garcia E, Garcia-Pedroza L, et al. (2005). An efficient, reproducible and fast preparation of 188Re-anti-CD20 for the treatment of non-Hodgkin's lymphoma. Nucl. Med. Commun. 26:793-799.
134. Goldrosen M H, Biddle W C, Pancock J, et al. (1990). Biodistribution, pharmacokinetic, and imaging studies with 186Re-labeled NR-LU-10 whole antibody in LS174T colonic tumor-bearing mice. Cancer Res. 24:7973-7978.
135. Visser G W, Gerretsen M, Herscheid J D, et al. (1993). Labeling of monoclonal antibodies with rhenium-186 using the MAG3 chelate for radioimmunotherapy of cancer:A technical protocol. J. Nucl. Med. 34:1953-1963.
136. Zamora P O, Gulhke S, Bender H, et al. (1996). Experimental radiotherapy of receptor- positive human prostate adenocarcinoma with 188Re-RC-160, a directly-radiolabeled somatostatin analogue. Int. J. Cancer. 65:214-220.
137. Safavy A, Khazaeli M B, Safavy K, et al. (1999). Biodistribution study of 188Re-labeled trisuccin-HuCC49 and trisuccin-HuCC49ΔCH2 conjugates in athymic nude mice bearing intraperitoneal colon cancer xenografts. Clin. Cancer Res. 5(suppl.):2994S-3000S.
138. Smith C J, Sieckman G L, Owen N K, et al. (2003). Radiochemical investigations of [188Re(H2O)(CO)3-diaminopropionic acid-SSS-bombesin(7-14)NH2]: Synthesis, radiolabeling and in vitro/in/vivo GRP receptor targeting studies. Anticancer Res. 23:63-70.
139. Lubberink M, Tolmachev V, Widström C, et al. (2002). 110mIn-DTPA-D-Phe1- octreotide for imaging of neuoendocrine tumors using PET. J. Nucl. Med. 43:1391-1397.
140. Tolmachev V, Bernhardt P, Forssell-Aronsson E, et al. (2000). 114mIn, a candidate for radionuclide therapy: low-energy cyclotron production and labeling of DTPA-D-Phe1- octreotide. Nucl. Med. Biol. 27:183-188.
141. Hnatowich D J, Childs R L, Lanteigne D, et al. (1983). The preparation of DTPAcoupled antibodies radiolabeled with metallic radionuclides: An improved method. J. Immunol. Meth. 65:147-157.
142. Krejcarek G E, Tucker K L (1977). Covalent attachment of chelating groups to macromolecules. Biochem. Biophys. Res. Commun. 77:581-585.
143. Brechbiel M W, Gansow O A, Atcher R W, et al. (1986). Synthesis of 1-(pisothiocyanatobenzyl) derivatives of DTPA and EDTA. Antibody labeling and tumorimaging studies. Inorg. Chem. 25:2772-2781.
144. Westerberg D A, Carney P L, Rogers P E, et al. (1988). Synthesis of novel bifunctional chelators and their use in preparing monoclonal antibody conjugates for tumor targeting. J. Med. Chem. 32:236-243.
145. Reilly R M, Scollard D A, Wang J, et al. (2004). A kit formulated under good manufacturing practices for labeling human epidermal growth factor with 111In for radiotherapeutic applications. J. Nucl. Med. 45(4):701-708.
146. Zoghbi S S, Neumann R D, Gottschalk A (1986). The ultrapurification of indium-111 for radiotracer studies. Invest. Radiol. 21:710-713.
147. Reilly R, Sheldon K, Marks A (1989). Labelling of monoclonal antibodies 10B, 8C, and M2A with indium-111. Int. J. Appl. Radiat. Isot. 40(4):279-283.
148. Carney P L, Rogers P E, Johnson D K (1989). Dual isotope study of iodine-125 and indium-111-labeled antibody in athymic mice. J. Nucl. Med. 30:374-384.
149. McLarty K, Cornelissen B, Scollard D, et al. (2006). Imaging of HER-2/neu positive human breast cancer xenografts in CD1nu/nu mice using 111In-labeled trastuzumab (Herceptin). Canadian Breast Cancer Research Alliance: Reasons for Hope Conf. Montreal, Quebec, Canada.
150. Hnatowich D J, Griffin T W, Kosciuczyk C, et al. (1985). Pharmacokinetics of an indium-111-labeled monoclonal antibody in cancer patients. J. Nucl. Med. 26:849-858.
151. Reilly R M, Marks A, Law J, et al. (1992). In-vitro stability of EDTA and DTPA immunoconjugates of monoclonal antibody 2G3 labelled with In-111. Appl. Radiat. Isot. 43:961-967.
152. Goodwin D A, Meares C F, McTigue M, et al. (1986). Metal decomposition rates of 111In-DTPA and EDTA conjugates of monoclonal antibodies in vivo. Nucl. Med. Commun. 7:831-838.
153. Reilly R M, Maiti P K, Kiarash R, et al. (2001). Rapid imaging of human melanoma xenografts using an scFv fragment of the human monoclonal antibody H11 labelled with 111In. Nucl. Med. Commun. 22(5):587-595.
154. Orlova A, Briskin A, Sjöström A, et al. (2000). Cellular processing of 125I- and 111Inlabeled epidermal growth factor (EGF) bound to cultured A431 tumor cells. Nucl. Med. Biol. 27:827-835.
155. Bakker W H, Albert R, Bruns C, et al. (1991). [111In-DTPA-D-Phe1]-octreotide, a potential radiopharmaceutical for imaging of somatostatin receptor-positive tumors:Synthesis, radiolabeling and in-vitro validation. Life. Sci. 49:1583-1591.
156. Cole W C, DeNardo S J, Meares C F, et al. (1987). Comparative serum stability of radiochelates for antibody radiopharmaceuticals. J. Nucl. Med. 28:83-90.
157. Deshpande S V, Subramanian R, McCall M J, et al. (1990). Metabolism of indium chelates attached to monoclonal antibody: Minimal transchelation of indium from benzyl-EDTA chelate in vivo. J. Nucl. Med. 31:218-224.
158. Blend M J, Greager J A, Atcher R W, et al. (1988). Improved sarcoma imaging and reduced hepatic activity with indium-111-SCN-Bz-DTPA linked to MoAb 19-24. J. Nucl. Med. 29:1810-1816.
159. Reilly R (2005). The immunoreactivity of radiolabeled antibodies-its impact on tumor targeting and strategies for preservation. Cancer Biother. Radiopharm. 19:669-672.
160. Rodwell J D, Alvarez V L, Lee C, et al. (1986). Site-specific covalent modification of monoclonal antibodies: In vitro and in vivo evaluation. Proc. Natl. Acad. Sci. USA. 83:2632-2636.
161. Abraham R, Moller D, Gabel D, et al. (1991). The influence of periodate oxidation on monoclonal antibody avidity and immunoreactivity. J. Immunol. Meth. 144:77-86.
162. King T P, Zhao S W, Lam T (1986). Preparation of protein conjugates via intermolecular hydrazone linkage. Biochem. 25(19):5774-5779.
163. Chan C, Sandhu J, Guha A, et al. (2005). A human transferrin-vascular endothelial growth factor (hnTf-VEGF) fusion protein containing an intergrated binding site for 111In for imaging tumor angiogenesis. J. Nucl. Med. 46:1745-1752.
164. Remy S, Reilly R M, Sheldon K, et al. (1995). A new radioligand for the epidermal growth-factor receptor-In-111 labeled human epidermal growth-factor derivatized with a bifunctional metal-chelating peptide. Bioconj. Chem. 6(6):683-690.
165. Wang J, Chen P, Su Z F, et al. (2001). Amplified delivery of indium-111 to EGFRpositive human breast cancer cells. Nucl. Med. Biol. 28(8):895-902.
166. Manabe Y, Longley C, Furnanski P (1986). High-level conjugation of chelating agents onto immunoglobulins: Use of an intermediary poly(L-lysine)-diethylenetriaminepentaacetic acid carrier. Biochim. Biophys. Acta. 883:460.
167. Kobayashi H, Sato N, Saga T, et al. (2000). Monoclonal antibody-dendrimer conjugates enable radiolabeling of antibody with markedly high specific activity with minimal loss of immunoreactivity. Eur. J. Nucl. Med. 27:1334-1339.
168. Wen X, Wu Q-P, Lu Y, et al. (2001). Poly(ethylene glycol)-conjugated anti-EGF receptor antibody C225 with radiometal chelator attached to the termini of polymer chains. Bioconjug. Chem. 12:545-553.
169. Wen X, Wu Q-P, Ke S, et al. (2001). Conjugation with 111In-DTPA-poly(ethylene glycol) improves imaging of anti-EGF receptor antibody C225. J. Nucl. Med. 42:1530-1537.
170. Duncan J R, Welch M J (1993). Intracellular metabolism of indium-111-DTPA labeled receptor targeted proteins. J. Nucl. Med. 34:1728-1738.
171. Rogers B E, Franano F N, Duncan J R, et al. (1995). Identification of metabolites of 111In-diethylenetriaminepentaacetic acid-monoclonal antibodies and antibody fragments in vivo. Cancer Res. 55:5714-5720S.
172. Akizawa H, Arano Y, Uezono T, et al. (1998). Renal metabolism of 111In-DTPA-DPhe1- octreotide in vivo. Bioconjug. Chem. 9:662-670.
173. Bass L A, Lanahan M V, Duncan J R, et al. (1998). Identification of the soluble in vivo metabolites of indium-111-diethylenetriaminepentaacetic acid-D-Phe1- octreotide. Bioconjug. Chem. 9:192-200.
174. Lewis M R, Raubitschek A, Shively J E (1994). A facile, water-soluble method for modification of proteins with DOTA. Use of elevated temperature and optimized pH to achieve high specific activity and high chelate stability in radio labeled immunoconjugates. Bioconjug. Chem. 5:565-576.
175. de Jong M, Bakker W H, Krenning E P, et al. (1997). Yttrium-90 and indium-111 labelling, receptor binding and biodistribution of [DOTA0,D-Phe1,Tyr3]octreotide, a promising somatostatin analogue for radionuclide therapy. Eur. J. Nucl. Med. 24:368-371.
176. Williams L E, Lewis M R, Bebb G C, et al. (1998). Biodistribution of 111In- and 90Ylabeled DOTA and maleimidocysteinamido-DOTA ocnjugated to chimeric anticarcinoembryonic antigen antibody in xenograft-bearing nude mice: comparison of stable and chemically labile linker systems. Bioconjug. Chem. 9:87-93.
177. Tsai S W, Li L, Williams L E, Anderson A L, et al. (2001). Metabolism and renal clearance of 111In-labeled DOTA-conjugated antibody fragments. Bioconjug. Chem. 12:264-270.
178. Li L, Olafsen T, Anderson A L, et al. (2002). Reduction of kidney uptake in radiometal labeled peptide linkers conjugated to recombinant antibody fragments. Sitespecific conjugation of DOTA-peptides to a Cys-diabody. Bioconjug. Chem. 13:985-995.
179. Cremonesi M, Ferrari M, Zoboli S, et al. (1999). Biokinetics and dosimetry in patients administered with 111In-DOTA-Tyr3-octreotide: Implications for internal radiotherapy with 90Y-DOTATOC. Eur. J. Nucl. Med. 26:877-886.
180. Onthank D C, Liu S, Silva P J, et al. (2004). 90Y and 111In complexes of a DOTAconjugated integrin αvβ3 receptor antagonist: different but biologically equivalent. Bioconjug. Chem. 15:235-241.
181. Yoo J, Tang L, Perkins T A, et al. (2005). Preparation of high specific activity 86Y using a small biomedical cyclotron. Nucl. Med. Biol. 32:891-897.
182. Chinol M, Hnatowich D J (1987). Generator-produced yttrium-90 for radioimmunotherapy. J. Nucl. Med. 28:1465-1470.
183. Harwood S J, Gibbons L K, Goldner P J, et al. (2002). Outpatient radioimmunotherapy with Bexxar. Cancer. 94:1358-1362.
184. Garmestani K, Milenic D E, Plascjak P S, et al. (2002). A new and convenient method for purification of 86Y using a Sr(II) selective resin and comparison of biodistribution of 86Y and 111In labeled HerceptinTM. Nucl. Med. Biol. 29:599-606.
185. Liu S, Edwards D S (2001). Bifunctional chelators for therapeutic lanthanide radiopharmaceuticals. Bioconjug. Chem. 12:7-34.
186. Hnatowich D J, Virzi F, Doherty P W (1985). DTPA-coupled antibodies labeled with yttrium-90. J. Nucl. Med. 26:503-509.
187. Brouwers A H, van Eerd J E M, Frielink C, et al. (2004). Optimization of radioimmunotherapy of renal cell carcinoma: labeling of monoclonal antibody cG250 with 131I, 90Y, 177Lu or 186Re. J. Nucl. Med. 45:327-337.
188. Griffiths G L, Govindan S V, Sharkey R M, et al. (2003). 90Y-DOTA-hLL2: An agent for radioimmunotherapy of non-Hodgkin's lymphoma. J. Nucl. Med. 44:77-84.
189. Deshpande S V, DeNardo S J, Kukis D L, et al. (1990). Yttrium-90-labeled monoclonal antibody for therapy: Labeling by a new macrocyclic bifunctional chelating agent. J. Nucl. Med. 31:473-479.
190. McCall M J, Diril H, Meares C F (1990). Simplified method for conjugating macrocyclic bifunctional chelating agents to antibodies via 2-iminothiolane. Bioconjug. Chem. 1:222-226.
191. Lewis M R, Kao J Y, Anderson A-L J, et al. (2001). An improved method for conjugating monoclonal antibodies with N-hydroxysulfosuccinimidyl DOTA. Bioconjug. Chem. 12:320-324.
192. Kukis D L, DeNardo S J, DeNardo G L, et al. (1998). Optimized conditions for chelation of yttrium-90-DOTA immunoconjugates. J. Nucl. Med. 39:2105-2110.
193. Breeman W A P, de Jong M, Visser T J, et al. (2003). Optimising conditions for radiolabelling of DOTA-peptides with 90Y, 111In and 177Lu at high specific activities. Eur. J. Nucl. Med. Mol. Imaging. 30:917-920.
194. Hainsworth J E S, Mather S J (2005). Regressive DOTA labelling performance with indium-111 and yttrium-90 over a week of use. Eur. J. Nucl. Med. Mol. Imaging. 32:1348.
195. Salako Q A, O'Donnell R T, DeNardo S J (1998). Effects of radiolysis on yttrium-90- labeled Lym-1 antibody preparations. J. Nucl. Med. 39:667-670.
196. Liu S, Edwards D S (2001). Stabilization of 90Y-labeled DOTA-biomolecule conjugates using gentisic acid and ascorbic acid. Bioconjug. Chem. 12:554-558.
197. Liu S, Ellars C E, Edwards D S (2003). Ascorbic acid: Useful as a buffer agent and radiolytic stabilizer for metalloradiopharmaceuticals. Bioconjug. Chem. 14:1052-1056.
198. Kosmas C, Snook D, Gooden C S, et al. (1992). Development of humoral immune responses against a macrocyclic chelating agent (DOTA) in cancer patients receiving radioimmunoconjugates for imaging and therapy. Cancer Res. 52:904-911.
199. Watanabe N, Goodwin D A, Meares C F, et al. (1994). Immmunogenicity in rabbits and mice of an antibody-chelate conjugate: Comparison of (S) and (R) macrocyclic enantiomers and an acyclic chelating agent. Cancer Res. 54:1049-1054.
200. DeNardo G L, Mirick G R, Kroger L A, et al. (1996). Antibody responses to macrocycles in lymphoma. J. Nucl. Med. 37:451-456.
201. Perico M E, Chinol M, Nacca A, et al. (2001). The humoral immune response to macrocyclic chelating agent DOTA depends on the carrier molecule. J. Nucl. Med. 42:1697-1703.
202. Saha G B (2004). Diagnostic uses of radiopharmaceuticals in nuclear medicine. In Fundamentals of Nuclear Pharmacy, 5th ed. Springer, New York, 247-329.
203. Michel R B, Brechbiel M W, Mattes M J (2003). A comparison of 4 radionuclides conjugated to antibodies for single-cell kill. J. Nucl. Med. 44:632-640.
204. Maecke H R, Hofmann M, Haberkorn U (2005). 68Ga-labeled peptides in tumor imaging. J. Nucl. Med. 46:172S-178S.
205. Schumacher J, Maier-Borst W (1981). A new 68Ge/68Ga radioisotope generator system for production of 68Ga in dilute HCl. Int. J. Appl. Radiat. Isot. 32:31-36.
206. Ugur O, Kothari P J, Finn R D, et al. (2002). Ga-66 labeled somatostatin analogue DOTA-D-Phe1-Tyr3-octreotide as a potential agent for positron emission tomography imaging and receptor mediated internal radiotherapy of somatostatin receptor positive tumors. Nucl. Med. Biol. 29:147-157.
207. Smith-Jones P M, Stolz B, Bruns C, et al. (1994). Gallium-67/gallium-68-[DFO]- octreotide-a potential radiopharmaceutical for PET imaging of somatostatin receptorpositive tumors: Synthesis and radiolabeling in vitro and preliminary in vivo studies. J. Nucl. Med. 35:317-325.
208. Breeman W A P, de Jong M, de Blois E, et al. (2005). Radiolabelling DOTA-peptides with 68Ga. Eur. J. Nucl. Med. Mol. Imaging. 32:478-485.
209. Henze M, Schuhmacher J, Hipp P, et al. (2001). PET imaging of somatostatin receptors using [68Ga]DOTA-D-Phe1-Tyr3-octreotide: First results in patients with meningiomas. J. Nucl. Med. 42:1053-1056.
210. Velikyan I, Beyer G L, Langström B (2004). Microwave-supported preparation of 68Ga bioconjugates with high specific activity. Bioconjug. Chem. 15:554-560.
211. Reubi J C, Schar J-C, Waser B, et al. (2000). Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur. J. Nucl. Med. 27:273-282.
212. Hofmann M, Maecke H, Börner A R, et al. (2001). Biokinetics and imaging with the somatostatin receptor PET radioligand 68Ga-DOTATOC: preliminary data. Eur. J. Nucl. Med. 28:1751-1757.
213. Wild D, Macke H R, Waser B, et al. (2005). 68Ga-DOTANOC: A first compound for PET imaging with high affinity for somatostatin receptor subtypes 2 and 5. Eur. J. Nucl. Med. Mol. Imaging. 32:724.
214. Froideveaux S, Calame-Christe M, Schumacher J, et al. (2004). A gallium-labeled DOTA-α-melanocyte-stimulating hormone analog for PET imaging of melanoma metastases. J. Nucl. Med. 45:116-123.
215. Velikyan I, Sundberg ÄL, Lindhe Ö, et al. (2005). Preparation and evaluation of 68Ga-DOTA-hEGF for visualization of EGFR expression in malignant tumors. J. Nucl. Med. 46:1881-1888.
216. Blower P J, Lewis J S, Zweit J (1996). Copper radionuclides and radiopharmaceuticals in nuclear medicine. Nucl. Med. Biol. 23:957-980.
217. Anderson C J, Jones A L, Bass L A, et al. (1998). Radiotherapy, toxicity and dosimetry of copper-64-TETA-octreotide in tumor-bearing rats. J. Nucl. Med. 39:1944-1951.
218. Connett J M, Anderson C J, Guo L Y, et al. (1996). Radioimmunotherapy with a 64Cu-labeled monoclonal antibody: a comparison with 67Cu. Proc. Natl. Acad. Sci. USA. 93:6814-6818.
219. McCarthy D W, Shefer R E, et al. (1997). Efficient production of high specific activity 64Cu using a biomedical cyclotron. Nucl. Med. Biol. 24:35-43.
220. Obata A, Kasamatsu S, McCarthy D W, et al. (2003). Production of therapeutic quantities of 64Cu using a 12 MeV cyclotron. Nucl. Med. Biol. 30:535-539.
221. Williams H A, Robinson S, Julyan P, et al. (2005). A comparison of PET imaging characteristics of various copper radioisotopes. Eur. J. Nucl. Med. Mol. Imaging. 32:1473-1480.
222. McCarthy D W, Bass L A, Cutler P D, et al. (1999). High purity production and potential applications of copper-60 and copper-61. Nucl. Med. Biol. 26:351-358.
223. Novak-Hofer I, Schubiger P A (2002). Copper-67 as a therapeutic nuclide for radioimmunotherapy. Eur. J. Nucl. Med. 29:821-830.
224. Cole W C, DeNardo S J, Meares C F, et al. (1986). Serum stability of 67Cu chelates:comparison with 111In and 57Co. Nucl. Med. Biol. 13:363-368.
225. Anderson C J, Schwarz S W, Connett J M, et al. (1995). Preparation, biodistribution and dosimetry of copper-64-labeled anti-colorectal carcinoma monoclonal antibody fragments 1A3-F(ab′)2. J. Nucl. Med. 36:850-858.
226. Lewis J S, Srinivasan A, Schmidt M A, et al. (1999). In vitro and in vivo evaluation of 64Cu-TETA-Tyr3-octreotate. A new somatostatin analog with improved target tissue uptake. Nucl. Med. Biol. 26:267-273.
227. Li W P, Lewis J S, Kim J, et al. (2002). DOTA-D-Tyr1-octreotate: A somatostatin analogue for labeling with metal and halogen radionuclides for cancer imaging and therapy. Bioconjug. Chem. 13:721-728.
228. O'Donnell R T, DeNardo G L, Kukis D L, et al. (1999). A clinical trial of radioimmunotherapy with 67Cu-2-IT-BAT-Lym-1 for non-Hodgkin's lymphoma. J. Nucl. Med. 40:2014-2020.
229. Philpott G W, Schwarz S W, Anderson C J, et al. (1995). RadioimmunoPET: detection of colorectal carcinoma with positron-emitting copper-64-labeled monoclonal antibody. J. Nucl. Med. 36:1818-1824.
230. Anderson C J, Dehdashti F, Cutler P D, et al. (2001). 64Cu-TETA-octreotide as a PET imaging agent for patients with neuroendocrine tumors. J. Nucl. Med. 42:213-221.
231. Anderson C J, Pajeau T S, Edwards W B, et al. (1995). In vitro and in vivo evaluation of copper-64-octreotide conjugates. J. Nucl. Med. 36:2315-2325.
232. Chen X, Hou Y, Tohme M, et al. (2004). Pegylated Arg-Gly-Asp peptide: 64Cu labeling and PET imaging of brain tumor αvβ3-integrin expression. J. Nucl. Med. 45:1776-1783.
233. Thakur M L, Aruva M R, Gariepy J, et al. (2004). PET imaging of oncogene overexpression using 64Cu-vasoactve intestinal peptide (VIP) analog: comparison with 99mTc-VIP analog. J. Nucl. Med. 45:1381-1389.
234. Rogers B E, Bigott H M, McCarthy D W, et al. (2003). MicroPET imaging of a gastrinreleasing peptide receptor-positive tumor in a mouse model of human prostate cancer using a 64Cu-labeled bombesin analogue. Bioconjug. Chem. 14:756-763.
235. Rogers B E, Anderson C J, Connett J M, et al. (1996). Comparison of four bifunctional chelates for radiolabeling monoclonal antibodies with copper radioisotopes: biodistribution and metabolism. Bioconjug. Chem. 7:511-522.
236. Bass L A, Wang M, Welch M J, et al. (2000). In vivo transchelation of copper-64 from TETA-octreotide to superoxide dismutase in rat liver. Bioconjug. Chem. 11:527-532.
237. Mirick G R, O'Donnell R T, DeNardo S J, et al. (1999). Transfer of copper from a chelated 67Cu-antibody conjugate to ceruloplasmin in lymphoma patients. Nucl. Med. Biol. 26:841-845.
238. Milenic D E, Garmestani K, Chappell L L, et al. (2002). In vivo comparison of macrocyclic and acyclic ligands for radiolabeling of monoclonal antibodies with 177Lu for radioimmunotherapeutic applications. Nucl. Med. Biol. 29:431-442.
239. Mulligan T, Carrasquillo J A, Chung Y, et al. (1995). Phase I study of intravenous 177Lu-labeled CC49 murine monoclonal antibody in patients with advanced adenocarcinoma. Clin. Cancer Res. 1:1447-1454.
240. Müller W A, Linzner U, Schäffer E H (1978). Organ distribution studies of lutetium-177 in mouse. Int. J. Nucl. Med. Biol. 5:29-31.
241. Breeman W A P, van der Wansem K, Bernard B F, et al. (2003). The addition of DTPA to [177Lu-DOTA0,Tyr3]octreotate prior to administration reduces rat skeleton uptake of radioactivity. Eur. J. Nucl. Med. 30(312):315.
242. Alvarez R D, Partridge E E, Khazaeli M B, et al. (1997). Intraperitoneal radioimmunotherapy of ovarian cancer with 177Lu-CC49: A phase I/II study. Gynecol. Oncol. 65:94-101.
243. Chauhan S C, Jain M, Moore E D, et al. (2005). Pharmacokinetics and biodistributon of 177Lu-labeled multivalent single-chain Fv construct of the pancarcinoma monoclonal antibody CC49. Eur. J. Nucl. Med. Mol. Imaging. 32:264-273.
244. McDevitt M R, Dangshe M, Lai L, et al. (2001). Tumor therapy with targeted atomic nanogenerators. Science. 294:1537-1540.
245. Miederer M, McDevitt M R, Sgouros G, et al. (2004). Pharmacokinetics, dosimetry, and toxicity of the targetable atomic generator, 225Ac-HuM195, in nonhuman primates. J. Nucl. Med. 45:129-137.
246. Milenic D E, Roselli M, Mirzadeh S, et al. (2001). In vivo evaluation of bismuthlabeled monoclonal antibody comparing DTPA-derived bifunctional chelates. Cancer Biother. Radiopharm. 16:133-146.
247. Yao Z, Garmestani K, Wong K J, et al. (2001). Comparative cellular catabolism and retention of astatine-, bismuth-, and lead-radiolabeled internalizing monoclonal antibody. J. Nucl. Med. 42:1538-1544.
248. Ballangrud A M, Yang W-H, Palm S, et al. (2004). Alpha-particle emitting atomic generator (actinium-225)-labeled trastuzumab (Herceptin) targeting of breast cancer spheroids: Efficacy versus HER2/neu expression. Clin. Cancer Res. 10:4489-4497.
249. Horak E, Hartmann F, Garmestani K, et al. (1997). Radioimmunotherapy targeting of HER2/neu oncoprotein on ovarian tumor using lead-212-DOTA-AE1. J. Nucl. Med. 38:1944-1950.
250. Meares C F, McCall M J, Rearden D T, et al. (1984). Conjugation of antibodies with bifunctional chelating agents: isothiocyanate and bromoacetamide reagents: Methods of analysis and subsequent addition of metal ions. Anal. Biochem. 142:68.
251. Pippin C J, Parker T A, McMurry T J, et al. (1992). Spectrophotometric method for the determination of a bifunctional DTPA ligand in DTPA-monoclonal antibody conjugates. Bioconjug. Chem. 3:342-345.
252. Hartikka M, Vihko P, Södervall M, et al. (1989). Radiolabelling of monoclonal antibodies:Optimization of conjugation of DTPA to F(ab′)2-fragments and a novel measurement of the degree of conjugation using Eu(III) labelling. Eur. J. Nucl. Med. 15:157-161.
253. Pham D T, Kaspersen F M, Bos E S (1995). Electrophoretic method for the quantitative determination of a benzyl-DTPA ligand in DTPA monoclonal antibody conjugates. Bioconjug. Chem. 6:313-315.
254. Dadachova E, Chappell L L, Brechbiel M W (1999). Spectrophotometric method for determination of bifunctional macrocyclic ligands in macrocyclic ligand-protein conjugates. Nucl. Med. Biol. 26:977-982.
255. Breeman W A P, de jong M T h M, de Jong M, et al. (2004). Reduction of skeletal accumulation of radioactivity by co-injection of DTPA in [90Y-DOTA0,Tyr3]octreotide solutions containing free 90Y3+. Nucl. Med. Biol. 31:821-824.
256. Lindmo T, Boven E, Cuttitta F, et al. (1984). Determination of the immunoreactive fraction of radiolabelled monoclonal antibodies by linear extrapolation of binding to infinite antigen excess. J. Immunol. Meth. 72:77-89.
257. Mardirossian G, Wu C, Rusckowski M, et al. (1992). The stability of 99Tcm directly labelled to an Fab′ antibody via stannous ion and mercaptoethanol reduction. Nucl. Med. Commun. 13:503-512.
258. Chen P, Cameron R, Wang J, et al. (2003). Antitumor effects and normal tissue toxicity of 111In-labeled epidermal growth factor administered to athymic mice bearing epidermal growth factor receptor-positive human breast cancer xenografts. J. Nucl. Med. 44(9):1469-1478.
259. Sharkey R M, Karacay H, Chang C H, et al. (2005). Improved therapy of non-Hodgkin's lymphoma xenografts using radionuclides pretargeted with a new anti-CD20 bispecific antibody. Leukemia. 19:1064-1069.
260. Michel R B, Rosario A V, Brechbiel M W, et al. (2003). Experimental therapy of disseminated B-cell lymphoma xenografts with 213Bi-labeled anti-CD74. Nucl. Med. Biol. 30:715-723.
261. Bonnet D, Bhatia M, Wang J Y C, et al. (1999). Cytokine treatment or accessory cells are required to initiate engraftment of purified primitive human hematopoietic cells transplanted at limiting doses into NOD/SCID mice. Bone. Marrow. Transplant. 23:203-209.
262. Iwata K, MacDonald L R, Hwang A B, et al. (2002). CT-SPECT for small animal imaging with A-SPECT. J. Nucl. Med. 43(suppl.):10P-Abst. No. 35.
263. Lewis J S, Achilefu S, Garbow J R, et al. (2002). Small animal imaging: Current technology and perspectives for oncological imaging. Eur. J. Cancer. 38:2173-2188.
264. Stabin M G, Sparks R B, Crowe E (2005). OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. J. Nucl. Med. 46:1023-1027.
265. Reilly R M, Chen P, Wang J, et al. (2006). Preclinical pharmacokinetic, biodistribution, toxicology and dosimetry studies of 111In-DTPA-hEGF-an Auger electronemitting radiotherapeutic agent for EGFR-positive breast cancer. J. Nucl. Med. In press.