Radiosynthesis of the iodine-124 labeled Hsp90 inhibitor PU-H71. Academic Article uri icon

Overview

abstract

  • 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 [(124)I]-PU-H71(5); this was synthesized from the corresponding Boc-protected stannane precursor 3 by iododestannylation with [(124)I]-NaI using chloramine-T as an oxidant for 2 min, followed by Boc deprotection with 6 N HCl at 50 °C for 30 min 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 980 mCi/µmol. Our report sets the stage for the introduction of [(124)I]-PU-H71 as a potential non-invasive probe for understanding biodistribution and pharmacokinetics of PU-H71 in living subjects using positron emission tomography imaging.

publication date

  • January 25, 2016

Research

keywords

  • Benzodioxoles
  • Iodine Radioisotopes
  • Purines
  • Radiopharmaceuticals

Identity

PubMed Central ID

  • PMC4779400

Scopus Document Identifier

  • 84959493014

Digital Object Identifier (DOI)

  • 10.1002/jlcr.3369

PubMed ID

  • 26806023

Additional Document Info

volume

  • 59

issue

  • 3