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The Quarterly Journal of Nuclear Medicine and Molecular Imaging 2013 Jun 19


lingua: Inglese

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

De Blois E. 1, Schroeder R. P. J. 1, 2, De Ridder C. M. A. 2, Van Weerden W. M. 2, Breeman W. A. P. 1, De Jong M. 1, 3

1 Department of Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands; 2 Department of Urology, Erasmus MC, Rotterdam, The Netherlands; 3 Department of Radiology, Erasmus MC, Rotterdam, The Netherlands


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 GRPR-mediated imaging we investigated the impact of various experimental conditions on pharmacokinetics using the 111In-labelled bombesin (BN) analogue DOTA-AMBA that binds to the GRPR with high affinity. Besides the frequently used PC-3 cell line, the androgen sensitive VCaP celline was used as human PC xenografts in nude mice.
Methods: Non-purified [111In]DOTA-AMBA was compared with HPLC-purified [111In]DOTA-AMBA. Effect of specific activity was studied administrating a constant amount of activity (0.1 MBq) [111In]DOTA-AMBA supplemented with different amounts of DOTA-AMBA (1-3000 pmol). GRPR was saturated with Tyr4-Bombesin, 1 and 4h prior to injection of [111In]DOTA-AMBA.
Results: GRPR-positive tumor tissue showed a significant 2 to 3-fold increase in absolute uptake after HPLC-purification while a stable tumor-to-pancreas ratio remained. Low peptide amounts (10 pmoles) resulted in a decline in uptake of 43% in tumor, 49% in kidney and 92% in pancreas. Tumor-to-pancreas ratio improved six-fold from 0.1±0 at 10 pmol up to 0.6±0.2 at 3000 pmol (P<0.01). GRPR saturation 4h prior to injection of [111In]DOTA-AMBA resulted in improvement of the tumor-to-pancreas ratio from 0.10±0.3 to 0.22±0.2 (P<0.01) and tumor-to-kidney ratio increased from 0.92±0.16 up to 3.45±0.5 (P<0.01).
Conclusion: Besides specific peptide characteristics also the experimental conditions, such as HPLC-purification, variations in peptide mass and GRPR saturation prior to [111In]DOTA-AMBA administration affect radiopeptide pharmacokinetics. Experimental conditions therefore need to be carefully selected in order to compose standardised protocols for optimal targeting.

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