Radiosynthesis of the iodine-124 labeled Hsp90 inhibitor PU-H71 Journal Article
| Authors: | Taldone, T.; Zatorska, D.; Ochiana, S. O.; Smith-Jones, P.; Koziorowski, J.; Dunphy, M. P.; Zanzonico, P.; Bolaender, A.; Lewis, J. S.; Larson, S. M.; Chiosis, G.; Pillarsetty, N. V. K. |
| Article Title: | Radiosynthesis of the iodine-124 labeled Hsp90 inhibitor PU-H71 |
| 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 [124I]-PU-H71(5); this was synthesized from the corresponding Boc-protected stannane precursor 3 by iododestannylation with [124I]-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 [124I]-PU-H71 as a potential non-invasive probe for understanding biodistribution and pharmacokinetics of PU-H71 in living subjects using positron emission tomography imaging. © Copyright 2016 John Wiley & Sons, Ltd. |
| Keywords: | heat shock protein 90; pet; purine; pu-h71; radiotracer; iodine-124; iododestannylation; cancer |
| Journal Title: | Journal of Labelled Compounds and Radiopharmaceuticals |
| Volume: | 59 |
| Issue: | 3 |
| ISSN: | 0362-4803 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2016-03-01 |
| Start Page: | 129 |
| End Page: | 132 |
| Language: | English |
| DOI: | 10.1002/jlcr.3369 |
| PROVIDER: | scopus |
| PMCID: | PMC4779400 |
| PUBMED: | 26806023 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 4 April 2016 -- Source: Scopus |
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MSK Authors
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133Pillarsetty -
11Koziorowski -
81Dunphy -
356Zanzonico -
67
Smith-Jones -
279Chiosis -
93Taldone -
456Lewis -
959Larson -
17
Zatorska -
15Ochiana -
17Bolaender
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