| Improving radiopeptide pharmacokinetics by adjusting experimental conditions for bombesin receptor-targeted imaging of prostate cancer. | |
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MedLine Citation:
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PMID: 23069925 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article |
Journal Detail:
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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:
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Created Date: 2012-10-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101213861 Medline TA: Q J Nucl Med Mol Imaging Country: Italy |
Other Details:
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Languages: eng Pagination: 468-75 Citation Subset: IM |
Affiliation:
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Department of Nuclear Medicine, Erasmus MC, Rotterdam, the Netherlands, Department of Urology, Erasmus MCRotterdam, the Netherlands - m.hendriks-dejong@erasmusmc.nl. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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