Document Detail

Improving radiopeptide pharmacokinetics by adjusting experimental conditions for bombesin receptor-targeted imaging of prostate cancer.
MedLine Citation:
PMID:  23069925     Owner:  NLM     Status:  In-Data-Review    
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 [111In]AMBA was compared with HPLC-purified [111In]AMBA. Effect of specific activity was studied administrating 0.1MBq [111In]AMBA supplemented with different amounts of AMBA (1-3000pmol). GRPR was saturated with Tyr4-BN 1 and 4h prior to injection of [111In]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 [111In]AMBA injection tumor-to-pancreas ratio improved from 0.10±0.3 to 0.22±0.2 (P<0.01) and tumor-to-kidney ratio increased from 0.92±0.16 to 3.45±0.5 (P<0.01).
CONCLUSION: Besides specific peptide characteristics also the experimental conditions, such as HPLC-purification, variations in specific activity and saturation of the GRPR prior to [111In]AMBA administration essentially affect radiopeptide pharmacokinetics. Experimental conditions therefore need to be carefully selected in order to compose ideal standardised protocols for optimal targeting.
R P J Schroeder; E De Blois; C M A De Ridder; W M Van Weerden; W A P Breeman; M de Jong
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of Radiopharmaceutical Chemistry and Biology     Volume:  56     ISSN:  1824-4785     ISO Abbreviation:  Q J Nucl Med Mol Imaging     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101213861     Medline TA:  Q J Nucl Med Mol Imaging     Country:  Italy    
Other Details:
Languages:  eng     Pagination:  468-75     Citation Subset:  IM    
Department of Nuclear Medicine, Erasmus MC, Rotterdam, the Netherlands, Department of Urology, Erasmus MCRotterdam, the Netherlands -
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