Abstract
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Objectives Recently, two new radiolabeled BB2r antagonists (111In-DOTA-8-Aoc-[D-Phe6,Leu-NH-Et13, desMet14]BBN[6-14] by Hoffman and co-workers and 111In-DOTA-4-amino-1-carboxymethyl-piperidine-[D-Phe6,Sta13,Leu-NH214]BBN[6-14] by Maecke and co-workers) were independently evaluated in prostate cancer models. Although both compounds exhibited similar in vitro receptor affinities, the statine BB2r antagonist was reported to have nearly 5 fold higher tumor avidity as compared to the ethyl amidated BB2r antagonist. Our objective was to perform a controlled side-by-side evaluation of both compounds in an identical model of prostate cancer.
Methods Peptides were synthesized using SPPS, characterized by LC-MS, and radiolabeled with 111In. Pharmacokinetic studies in PC-3 tumor bearing SCID mice were conducted at 15 min, 1, 4, and 24 hrs p.i. Micro-SPECT imaging was performed at 4 and 24 hrs p.i. for each 111In-BB2r antagonist.
Results The statine BB2r antagonist targeted PC-3 tumors with 7.96±2.71, 8.03±2.05, 7.21±1.59, and 5.80±1.72 %ID/g as compared to 6.69±1.18, 6.07±3.47, 3.61±1.09, and 0.59±0.26 %ID/g for the ethyl amidated BB2r antagonist at 15 min, 1, 4, and 24 hrs p.i. Renal and pancreatic clearance of the ethyl amidated BB2r antagonist was much more rapid than the statine BB2r antagonist. The ethyl amidated BB2r antagonist demonstrated superior early SPECT visualization (<4hrs p.i.) of prostate tumors while the statine BB2r antagonist excelled at delayed (>12 hrs p.i.) tumor visualization.
Conclusions Both 111In-BB2r antagonists allow visualization of BB2r expressing prostate cancer using micro-SPECT technology. Alkyl amidated BB2r antagonists may prove useful in the rapid clinical visualization of prostate cancer due to their rapid clearance from non-target tissues while statine BB2r antagonists offer the potential of delayed imaging of BB2r positive tissues in excess of 24 hrs p.i.
Research Support U.S. Dept. of Veterans Affairs Merit Revie