Development of site-directed radiopharmaceuticals for treatment of prostate cancer

Objectives The goal of this research project was to create a site-directed radiopharmaceutical reagent of bismuth-213 (5.87, 5.55 MeV α, t1/2 =45.6 min) with high specificity and affinity for targeting and treatment of human prostate tumors.

Methods We have designed a radiopharmaceutical conjugate of the formula [213Bi-CHXA-βala-BBN(7-14)] where CHXA = {[(R)-2-amino-3-(p-aminophenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-N,N,N',N'',N''-pentaacetic acid}, βala = β alanine, , and BBN(7-14) = bombesin peptide, synthesized using standard solid phase peptide synthesis techniques.

Results Synthetic preparation of the non-metallated CHXA-βala-BBN(7-14) conjugates occurs with CHXA-NHS active ester and commercially available βala-BBN reagent using EDC (1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide) and NHS (N-hydroxysuccinimide). Purification occurs using RP-HPLC. Mass spectrometry results verified synthesis of our new peptide conjugate.

Conclusions We are currently optimizing the synthesis of CHXA-βala-BBN and anticipate metallation with bismuth