Radiosynthesis of the iodine-124 labeled Hsp90 inhibitor PU-H71Show others and affiliations
2016 (English)In: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 59, no 3, p. 129-132Article in journal (Refereed) Published
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Text
Abstract [en]
Heat shock protein 90 (Hsp90) is an ATP dependent molecular chaperone protein whose function is critical for maintaining several key proteins involved in survival and proliferation of cancer cells. PU-H71 (1), is a potent purine-scaffold based ATP pocket binding Hsp90 inhibitor which has been shown to have potent activity in a broad range of in vivo cancer models and is currently in Phase I clinical trials in patients with advanced solid malignancies, lymphomas, and myeloproliferative neoplasms. In this report, we describe the radiosynthesis of [I-124]-PU-H71(5); this was synthesized from the corresponding Boc-protected stannane precursor 3 by iododestannylation with [I-124]-NaI using chloramine-T as an oxidant for 2min, followed by Boc deprotection with 6 N HCl at 50 degrees C for 30min to yield the final compound. The final product 5 was purified using HPLC and was isolated with an overall yield of 55 +/- 6% (n=6, isolated) from 3, and >98% purity and an average specific activity of 980mCi/mu mol. Our report sets the stage for the introduction of [I-124]-PU-H71 as a potential non-invasive probe for understanding biodistribution and pharmacokinetics of PU-H71 in living subjects using positron emission tomography imaging.
Place, publisher, year, edition, pages
WILEY-BLACKWELL , 2016. Vol. 59, no 3, p. 129-132
Keywords [en]
iodine-124; PU-H71; purine; heat shock protein 90; PET; radiotracer; cancer; iododestannylation
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-127055DOI: 10.1002/jlcr.3369ISI: 000372328200008PubMedID: 26806023OAI: oai:DiVA.org:liu-127055DiVA, id: diva2:919386
Note
Funding Agencies|David Rubenstein Center for Pancreatic Cancer Research; Susan G. Komen for the Cure; Department of Defense [PDF-BC093421]; MSKCC Brain Tumor Center; NIH Cancer Center Support Grant [2 P30 CA008748-48]; [P50-CA86438]; [R01 CA172546]; [R01 CA155226]; [P50 CA192937]; [R03-BC085588]
2016-04-132016-04-132017-04-24