Improving radiopeptide pharmacokinetics by adjusting experimental conditions for bombesin receptor-targeted imaging of prostate cancer

Aim. Prostate cancer (PC) is a major health problem. The Gastrin-Releasing Peptide Receptor (GRPR) offers a promising target for staging and monitoring of PC since it is overexpressed in PC and not in normal prostatic tissue. To improve receptor-mediated imaging we investigated the impact of various experimental conditions on pharmacokinetics using the Indium-111 labelled bombesin (BN) analogue AMBA. Besides frequently used androgen-resistant PC-3 also the clinically more relevant androgen sensitive VCaP celline was used as human PC xenograft in nude mice. Methods. Non-purified [In-111]AMBA was compared with HPLC-purified Fin In]AMBA. Effect of specific activity was studied administrating 0.1MBq [In-111] AMBA supplemented with different amounts of AMBA (1-3000pmol). GRPR was saturated with Tyr(4)-BN 1 and 4h prior to injection of [In-111]AMBA. Results. GRPR-positive tissue showed a significant 2 to 3-fold increase in absolute uptake after HPLC-purification while keeping a stable tumor-to-pancreas ratio. Lowering specific activity resulted in decline in uptake to 43% in tumor, 49% in kidney and 92% in pancreas between 10 and 3000 pmol. Tumor-to-pancreas ratio improved six-fold from 0.1 +/- 0 after 10 pmol up to 0.6 +/- 0.2 after 3000 pmol (P<0.01). When saturating GRPR 4h prior to [In-111]AMBA injection tumorto-pancreas ratio improved Conclusion. Besides specific peptide characteristics also the experimental conditions, such as HPLC-purification, variations in specific activity and saturation of the GRPR prior to [In-111]AMBA administration essentially affect radiopeptide pharmacokinetics. Experimental conditions therefore need to be carefully selected in order to compose ideal standardised protocols for optimal targeting.