Synthesis of 11C-labeled Kendine 91, a histone deacetylase inhibitor

• Published in: Applied radiation and isotopes Vol. 70; no. 10; pp. 2552 - 2557
• Main Authors: Aginagalde, Maialen, Gómez-Vallejo, Vanessa, Vara, Yosu, Cossío, Fernando P., Llop, Jordi
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-10-2012
• Subjects: Carbon Radioisotopes - chemistry; Carbon-11; Chromatography, Liquid; HDAC inhibitors; Histone Deacetylase Inhibitors - chemical synthesis; Hydroxamic Acids - chemical synthesis; Kendine 91; Magnetic Resonance Spectroscopy; PET; Pyrroles - chemical synthesis; HDAC inhibitors; Carbon-11; Kendine 91; PET
• ISSN: 0969-8043; 1872-9800
• DOI: 10.1016/j.apradiso.2012.05.016

In the present paper, the synthesis of 11C-labeled Kendine 91 (a HDAC inhibitor which has shown in vitro and in vivo activity in HCT 116 and MOLT 4 human cancer cell lines) is described for the first time. The radiosynthesis has been approached by reaction of the non-radioactive precursor 6-((3-(4-hydroxyphenyl)-5-phenyl-1H-pyrrole-2-carboxamide))hexanehydroxamic acid with [11C]CH3I in basic media. Despite the presence of more than one reactive site in the chemical structure of the precursor, acceptable radiochemical yield (8.2±2.1%, decay corrected to the end of bombardment), specific activity (28.2±9.4GBq/μmol) and radiochemical purity values (>95%) were obtained in reasonably short preparation times (∼40min). Despite the moderate radiochemical yield, final radioactivity and radioactivity concentration values (1.8±0.3GBq and 180MBq/ml, respectively) should be sufficient for putative in vivo studies in animals.
► We labeled Kendine 91 with carbon-11. ► Despite low yields final radioactivity should allow in vivo studies. ► We synthesized the desmethylated precursor using two routes. ► Microwave assisted Paal–Knorr reaction was more efficient than (3+2) cycloaddition.