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 [(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.
authors.affiliation: Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Tony
authors.initials: T
authors.lastname: Taldone
authors.affiliation: Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Danuta
authors.initials: D
authors.lastname: Zatorska
authors.affiliation: Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Stefan O
authors.initials: SO
authors.lastname: Ochiana
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Smith-Jones
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Jacek
authors.initials: J
authors.lastname: Koziorowski
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Dunphy
authors.affiliation: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Pat
authors.initials: P
authors.lastname: Zanzonico
authors.affiliation: Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Bolaender
authors.affiliation: Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.|Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lewis
authors.affiliation: Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.|Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Larson
authors.affiliation: Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Chiosis
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Naga Vara Kishore
authors.initials: NV
authors.lastname: Pillarsetty
mesh_terms: D052117:Benzodioxoles / Q000737:chemistry*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D007457:Iodine Radioisotopes / Q000737:chemistry*; D011687:Purines / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*
chemical_list: D052117:Benzodioxoles; D018841:HSP90 Heat-Shock Proteins; D007457:Iodine Radioisotopes; D011687:Purines; D019275:Radiopharmaceuticals; C526550:9H-purine-9-propanamine, 6-amino-8-((6-iodo-1,3-benzodioxol-5-yl)thio)-N-(1-methylethyl)-
keywords: PET; PU-H71; cancer; heat shock protein 90; iodine-124; iododestannylation; purine; radiotracer