Positioning of 99mTc-chelators influences radiolabeling, stability and biodistribution of Affibody molecules

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 14, 2009, Pages 3912-3914

  Ekblad, Torun ^a   Orlova, Anna ^b,c   Feldwisch, Joachim ^c   Wennborg, Anders ^c   Karlström, Amelie Eriksson ^a   Tolmachev, Vladimir ^b,c,d  

^a ALBANOVA UNIVERSITY CENTER   (Sweden)

^b UPPSALA UNIVERSITY   (Sweden)

^c Affibody AB   (Sweden)

^d UPPSALA UNIVERSITY   (Sweden)

Author keywords

Affibody molecule; Molecular imaging; Peptide synthesis; Tc chelator

Indexed keywords

CHELATING AGENT; MERCAPTOACETYLGLUTAMYLSERYLGLUTAMATE DERIVATIVE; MERCAPTOACETYLGLYCYLGLYCYLGLYCINE DERIVATIVE; MERCAPTOACETYLSERYLSERYLSERINE DERIVATIVE; PEPTIDE DERIVATIVE; TECHNETIUM 99M; THIOGLYCOLIC ACID DERIVATIVE; UNCLASSIFIED DRUG; AFFIBODY (ZHER2 342)2; AFFIBODY (ZHER2-342)2; EPIDERMAL GROWTH FACTOR RECEPTOR 2; HYBRID PROTEIN; N(EPSILON)49 MERCAPTOACETYL GLUTAMYL SERYL GLUTAMYL ZHER2 342; N(EPSILON)49 MERCAPTOACETYL GLYCYL GLYCYL GLYCYL ZHER2 342; N(EPSILON)49 MERCAPTOACETYL SERYL SERYL SERYL ZHER2 342; N(EPSILON)49-MERCAPTOACETYL-GLUTAMYL-SERYL-GLUTAMYL-ZHER2-342; N(EPSILON)49-MERCAPTOACETYL-GLYCYL-GLYCYL-GLYCYL-ZHER2-342; N(EPSILON)49-MERCAPTOACETYL-SERYL-SERYL-SERYL-ZHER2-342; TECHNETIUM COMPLEX;

ANIMAL EXPERIMENT; ANTIGEN BINDING; ARTICLE; BINDING AFFINITY; CHELATION; CONTROLLED STUDY; DRUG DISTRIBUTION; DRUG SPECIFICITY; DRUG STABILITY; ISOTOPE LABELING; MOLECULAR STABILITY; MOUSE; NONHUMAN; PEPTIDE SYNTHESIS; RADIOISOTOPE DISTRIBUTION; STRUCTURE ACTIVITY RELATION; ANIMAL; CHEMISTRY; HUMAN; METABOLISM; NUDE MOUSE; XENOGRAFT;

ANIMALS; CHELATING AGENTS; HUMANS; ISOTOPE LABELING; MICE; MICE, NUDE; ORGANOTECHNETIUM COMPOUNDS; RECEPTOR, ERBB-2; RECOMBINANT FUSION PROTEINS; TRANSPLANTATION, HETEROLOGOUS;

EID: 67649657953     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.03.083     Document Type: Article

References (20)

1. Orlova A., Feldwisch J., Abrahmsen L., and Tolmachev V. Cancer Biother. Radiopharm. 22 (2007) 573
2. Nygren P.A. FEBS J. 275 (2008) 2668
3. Orlova A., Magnusson M., Eriksson T.L., Nilsson M., Larsson B., Höidén-Guthenberg I., Widström C., Carlsson J., Tolmachev V., Ståhl S., and Nilsson F.Y. Cancer Res. 66 (2006) 4339
4. Tolmachev V. Curr. Pharm. Des. 14 (2008) 1
5. Baum R., Orlova A., Tolmachev V., and Feldwisch J. J. Nucl. Med. 47 (2006) 108
6. Engfeldt T., Renberg B., Brumer H., Nygren P.A., and Karlström A.E. ChemBioChem 6 (2005) 1043
7. Orlova A., Tolmachev V., Pehrson R., Lindborg M., Tran T., Sandström M., Nilsson F.Y., Wennborg A., Abrahmsén L., and Feldwisch J. Cancer Res. 67 (2007) 2178
8. Fortin M.A., Orlova A., Malmstrom P.U., and Tolmachev V. Int. J. Mol. Med. 19 (2007) 285
9. Engfeldt T., Tran T., Orlova A., Widström C., Feldwisch J., Abrahmsén L., Wennborg A., Karlström A.E., and Tolmachev V. Eur. J. Nucl. Med. Mol. Imaging 34 (2007) 1843
10. Tran T., Engfeldt T., Orlova A., Sandström M., Feldwisch J., Abrahmsén L., Wennborg A., Tolmachev V., and Karlström A.E. Bioconjugate Chem. 18 (2007) 1956
11. Ekblad T., Tran T., Orlova A., Widström C., Feldwisch J., Abrahmsén L., Wennborg A., Karlström A.E., and Tolmachev V. Eur. J. Nucl. Med. Mol. Imaging 35 (2008) 2245
12. Tran T.A., Ekblad T., Orlova A., Sandstrom M., Feldwisch J., Wennborg A., Abrahmsen L., Tolmachev V., and Eriksson Karlstrom A. Bioconjugate Chem. 19 (2008) 2568
13. Engfeldt T., Orlova A., Tran T., Bruskin A., Widström C., Karlström A.E., and Tolmachev V. Eur. J. Nucl. Med. Mol. Imaging 34 (2007) 722
14. Qu T., Wang Y., Zhu Z., Rusckowski M., and Hnatowich D.J. Nucl. Med. Commun. 22 (2001) 203
15. Mtt was removed by 8 × 2 min incubation in DCM with 1% TFA and 5% TIS.
16. Coupling reactions were performed using 5 equiv of amino acid or S-trityl-mercaptoacetic acid, 5 equiv HBTU/HOBt and 10 eq DIEA in NMP.
17. 3CN. A 20 min gradient of 25-45% B was used for purification of full-length proteins from the crude synthetic product. Purified proteins were lyophilized and analyzed in a 20 min elution gradient from 20% to 60% B.
18. 2O in 0.01 M HCl (1 mg/ml). To this mixture, 100 μl of fresh Tc-generator eluate was added and the mixture was incubated at room temperature for 60 min.
19. Instant thin layer chromatography was performed using glass fiber sheets impregnated with silica gel (ITLC SG, Gelman Sciences Inc.). The ITLC SG strips were eluted with PBS for yield and stability determinations, and with pyridine:acetic acid:water (5:3:1.5) to determine presence of reduced hydrolyzed technetium (RHT).
20. The animal study was performed in accordance with Swedish law and was approved by the Uppsala Committee of Animal Research Ethics.