The goal of this research is the development of tumor imaging and radiotherapeutic agents based on targeting of the integrin α_vβ₃ (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 α_vβ₃ (IC₅₀ = 12 and 18 nM, respectively), and good selectivity versus integrin α_IIbβ₃ (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.