Comparison of agonist and antagonist bombesin analogs for diagnostic imaging of prostate cancer

726 Objectives: The Bombesin peptide is a neuropeptide that has been shown to target the BB2 receptor (BB2r) which is expressed in a variety of neuroendocrine cancers, including prostate cancer. This presentation will evaluate the agonist (BBN(7-14)NH2) and antagonist ([(D)Phe6]BBN(7-13)NHEt) targeting vectors and compare the potential of the peptides to develop a SPECT imaging agent for prostate cancer. Methods: The conjugates, DOTA-8-AOC-BBN(7-14)NH2 and DOTA-8-AOC-[(D)Phe6]BBN(7-13)NHEt, were synthesized and radiolabeled with 111In. In vivo pharmacokinetic, microSPECT/CT and microMRI imaging studies were performed using PC-3 tumor bearing SCID mice. Results: The tumor retention of 6.66±2.00 and 6.58±0.73 %ID/g at 15 min p.i. decreased to 1.10 ± 0.23 and 2.02 ± 0.43 %ID/g by 4 hrs p.i. for the agonist and antagonist radioconjugates, respectively. At 4 hrs p.i., the [(D)Phe6]BBN(7-13)NHEt radioconjugate exhibited rapid renal clearance (97.10 ± 1.06 %ID) relative to the BBN(7-14)NH2 radioconjugate (78.27 ± 4.22 %ID). The antagonist radioconjugate also exhibited rapid non-target tissue clearance compared to the agonist radioconjugate resulting in significantly superior tumor to non-target tissue ratios at the 4hr p.i. timepoint. Micro-SPECT imaging performed at 1 and 4 hrs P.I. visualized uniquely discrete 111In activity only in BB2r expressing tumor tissue and bladder contents. Conclusions: 111In-DOTA-8-AOC-[(D)Phe6]BBN(7-13)NHEt demonstrates rapid clearance from non-target tissues resulting in significantly superior tumor imaging properties as compared to the corresponding 111In-BB2r agonist.