Radiosynthesis of the iodine-124 labeled Hsp90 inhibitor PU-H71

Ochiana, Stefan O. (author): Mem Sloan Kettering Cancer Centre, NY 10065 USA

Smith-Jones, Peter (author): Mem Sloan Kettering Cancer Centre, NY 10065 USA; Stony Brook School Med, NY USA; Stony Brook School Med, NY USA

Koziorowski, Jacek (author): Department of Radiology, Memorial Sloan Kettering Cancer Center, New York,NY, USA

Bolaender, Alexander (author): Mem Sloan Kettering Cancer Centre, NY 10065 USA

Lewis, Jason S. (author): Mem Sloan Kettering Cancer Centre, NY 10065 USA; Mem Sloan Kettering Cancer Centre, NY 10065 USA

Larson, Steven M. (author): Mem Sloan Kettering Cancer Centre, NY 10065 USA; Mem Sloan Kettering Cancer Centre, NY 10065 USA

Vara Kishore Pillarsetty, Naga (author): Mem Sloan Kettering Cancer Centre, NY 10065 USA

(creator_code:org_t)

2016-01-25
2016
English.
In: Journal of labelled compounds & radiopharmaceuticals. - : WILEY-BLACKWELL. - 0362-4803 .- 1099-1344. ; 59:3, s. 129-132

Related links:: https://europepmc.or...; show more...; https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Abstract Subject headings

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.

By the author/editor: Taldone, Tony; Zatorska, Danuta; Ochiana, Stefan ...; Smith-Jones, Pet ...; Koziorowski, Jac ...; Dunphy, Mark P.; show more...; Zanzonico, Pat; Bolaender, Alexa ...; Lewis, Jason S.; Larson, Steven M ...; Chiosis, Gabriel ...; Vara Kishore Pil ...; show less...

About the subject

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.