1. Design, Synthesis, and Evaluation of Radiolabeled Integrin αvβ3 Receptor Antagonists for Tumor Imaging and Radiotherapy.
- Author
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Thomas D. Harris, Shirley Kalogeropoulos, Tiffany Nguyen, Shuang Liu, Judit Bartis, Charles Ellars, Scott Edwards, David Onthank, Paula Silva, Padmaja Yalamanchili, Simon Robinson, Joel Lazewatsky, John Barrett, and Jeffrey Bozarth
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INTEGRINS , *TUMOR markers , *RADIOTHERAPY , *TUMOR growth - Abstract
The goal of this research is the development of tumor imaging and radiotherapeutic agents based on targeting of the integrin αvβ3 (vitronectin receptor). Macrocyclic chelator DOTA has been conjugated to peptidomimetic vitronectin receptor antagonist SH066 to give TA138. TA138 and 89Y-TA138 retain antagonist properties and high affinity for integrin αvβ3 (IC50 = 12 and 18 nM, respectively), and good selectivity versus integrin αIIbβ (IC50 > 10,000 nM). TA138 forms stable complexes with 111In and 90Y in > 95% RCP. 111In-TA138 demonstrates high tumor uptake in the c-neu Oncomouse® (Charles River Laboratories [Charles River, Canada]) mammary adenocarcinoma model (9.39% ID/g at 2 hours PI) and low background activity. Blood clearance is rapid and excretion is renal. Tumors are visible as early as 0.5 hours PI. Radiotherapy studies in the c-neu Oncomouse® model demonstrated a slowing of tumor growth at a dose of 15 mCi/m2, and a regression of tumors at a dose of 90 mCi/m2. 3 [ABSTRACT FROM AUTHOR]
- Published
- 2003
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