Direct synthesis of [DOTA-DPhe1]-octreotide and [DOTA-DPhe1,Tyr3]- octreotide (SMT487): Two conjugates for systemic delivery of radiotherapeutical nuclides to somatostatin receptor positive tumors in man

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 10, 1998, Pages 1207-1210

  Albert, Rainer ^a   Smith Jones, Peter ^a,b   Stolz, Barbara ^a   Simeon, Corinne ^a   Knecht, Hellmut ^a   Bruns, Christian ^a   Pless, Janos ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

^b MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

1,4,7,10 TETRAAZACYCLODODECANE N,N,N,N,TETRAACETIC ACID OCTREOTIDE[DEXTRO PHENYLALANINE 1 TYROSINE 3]; OCTREOTIDE; PENTETREOTIDE; PENTETREOTIDE IN 111; RADIOISOTOPE; SOMATOSTATIN DERIVATIVE; SOMATOSTATIN RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; DIAGNOSTIC VALUE; DRUG CONJUGATION; DRUG DELIVERY SYSTEM; HORMONE RECEPTOR INTERACTION; NONHUMAN; RADIATION DOSE; RAT; REACTION ANALYSIS; RECEPTOR BINDING; RECEPTOR DENSITY;

DRUG CARRIERS; HETEROCYCLIC COMPOUNDS, 1-RING; HUMANS; INDICATORS AND REAGENTS; IODINE RADIOISOTOPES; NEOPLASMS; OCTREOTIDE; RADIOPHARMACEUTICALS; RECEPTORS, SOMATOSTATIN; YTTRIUM RADIOISOTOPES;

ANIMALIA;

EID: 0032546524     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00187-5     Document Type: Article

References (16)

1. 1. Lamberts, S. W. J.; Krenning, E. P.; Reubi, J. C.; Endocr. Rev. 1991, 12, 450-482
2. 2. Bakker, W. H.; Albert, R.; Bruns, C.; Breeman, W. A. P.; Hofland, L. J.; Marbach, P.; Pless, J.; Pralet, D.; Stolz, B.; Koper, J. W.; Lamberts, S. W. J.; Visser, T. J.; Krenning, E. P. Life Sci. 1991, 49, 1583-1591
3. 3. Reichlin, S. New Engl. J. Med. 1983, 309, 1495-1563
4. 4. Bauer, W.; Briner, U.; Doepfner, W.; Haller, R.; Huguenin, R.; Marbach, P.; Petcher, T. J.; Pless, J. Life Sci., 1982, 31(11), 1133-40
5. 5. Krenning, E. P.; Kwekkeboom, D. J.; Bakker, W. H.; Breeman, W. A. P.; Kooij, P. P. M.; Oei, H. Y.; Van Hagen, P. M.; Postema, P. T. E.; DeJong, M.; Reubi, J. C.; Visser, T. J.; Teijs, A. E. M.; Hofland, L. J.; Koper, J.W.; Lamberts, S. W. J. Eur. J. Nucl. Med., 1993, 20, 283-292
6. 6. Smith-Jones, P.; Stolz, B.; Albert, R.; Knecht, H.; Bruns, C. Nucl. Med. Biol, 1997, 24, 761-769
7. 7. Béhé, M.; Heppeler, A.; Mäcke, H. R. European Association Nuclear Medicine Meeting. Copenhagen 1996, Abstract: OWe450
8. 2O (free acid) was purchased from the SYMAFEX company (France) and was used without further purification
9. 9. Mergler, M.; Hellstern, H.; Wirth, W.; Langer, W.; Prikoszowich W. American Peptide Symposium. Boston 1991, poster 12
10. 3CN/TFA as mobile phase, gave a pure and homogenous title compound in an overall yield of ∼40%.
11. 2)
12. 2O: 70/40/10/10 (for compound (III) and (IV))
13. t: 15.19 min. (III) and 13.66 min (IV)
14. 3CN (+0.1% AcOH) 100/0; mobile phase B: 20/80; Linear gradient: 0 % to 100 % B over 60 min.
15. 90Y-labelled SMT487 and various concentrations of competitor compound (30 μL). After the incubation for 60 min. at room temperature, the samples were filtered through glass-fibre filters which were presoaked with buffer containing 1% wt/vol BSA. The filters were then rinsed with 10 mL of ice-cold buffer; bound radioactivity was measured in a γ-counter. Specific binding was defined as the difference between total and non-specific binding in the presence of an excess (1 μM) of octreotide.
16. 17. Stolz, B.; Weckbecker, G.; Smith-Jones, P.; Albert, R.; Raulf, F.; H.; Bruns, C. Eur. J. Nucl. Med (submitted)