Radiosynthesis of the iodine-124 labeled Hsp90 inhibitor PU-H71
2016 (English)In: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 59, no 3, 129-132 p.Article in journal (Refereed) PublishedText
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, 129-132 p.
iodine-124; PU-H71; purine; heat shock protein 90; PET; radiotracer; cancer; iododestannylation
IdentifiersURN: urn:nbn:se:liu:diva-127055DOI: 10.1002/jlcr.3369ISI: 000372328200008PubMedID: 26806023OAI: oai:DiVA.org:liu-127055DiVA: diva2:919386
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]2016-04-132016-04-132016-04-13