Radiosynthesis And Biological Characterization Studies Of I-123 Labeled Iodosuberoylanilide Hydroxamic Acid (I-123-Isaha)

1485 Objectives Histone deacetylases (HDAC) is a key enzyme involved in epigenetic modifications. Suberoylanilide hydroxamic acid (SAHA) has been demonstrated an effective HDAC inhibitor. This study prepared 123I-4-iodosuberoylanilide hydroxamic acid (123I-ISAHA) as a novel scintigraphic probe for imaging HDAC and compared with that of 18F-FAHA. Methods 123I-ISAHA can be prepared with high radiochemical yield (≧95%, decay corrected) and radiochemical purity (≧98%) using oxidative iododestannylation reaction. Biological characterization studies including cellular uptake, metabolite analysis and scintigraphic imaging, were performed with a subcutaneous HepG2 hepatoma mouse model. Results The cellular accumulation (% total dose/106 cells) of 123I-ISAHA in HepG2 cells increased with time and reached the plateau after 4 h incubation (from 5.91±0.80 at 30 min post-incubation to 11.59±0.59 at 4 h), while that of 18F-FAHA rapidly decreased with time (from 0.14±0.02 at 15 min to 0.08±0.02 at 2 h) due to its high turnover rate. The in vivo stability of 123I-ISAHA (account for ~50% radioactivity in blood at 5 min post i.v. injection) was higher than that of 18F-FAHA (only less than 20% intact compound in blood at 30 s post i.v. injection). For in vivo imaging, the tumor-to-muscle ratio (T/M) of 123I-ISAHA derived from μSPECT imaging increased with time (from 1.08 at 0.25 h p.i. to 1.72 at 2 h p.i.), and the T/M of 18F-FAHA was 1.18 at 1 h p.i.. Conclusions A novel 123I-labeled HDAC inhibitor was successfully prepared and demonstrated as a promising SPECT probe that can image HDAC in HepG2 hepatoma cells. 123I-ISAHA may have potential for monitoring the therapeutic efficacy of HDAC inhibitors clinically