Preclinical assessment of [¹⁸F]-FAHA PET imaging as a novel biomarker for HDAC activity

Objectives The aim of this study was to assess the efficacy of PET imaging for HDAC activity with a novel radiotracer substrate 6-([¹⁸F]-fluoroacetamide)-1-hexanoicanilide ([¹⁸F]-FAHA). To investigate the applicability of [¹⁸F]-FAHA PET in clinical whole-body imaging, dynamic whole-body imaging with the [¹⁸F]-FAHA PET was preclinically performed in rhesus macaque.

Methods [¹⁸F]-FAHA was synthesized according to the methods developed in our laboratory in high specific activity. The animal studies were conducted with a total of five rhesus macaque monkeys (2 male and 3 female at body weight of 7.3+/-1.8kg). Under inhalation anesthesia with isoflurane, the animals were injected with [¹⁸F]-FAHA (183.9+/-18.1MBq, i.v.) and dynamic PET were acquired in first 30 min with 2D mode acquisition, followed by 3-set of whole body static scans were performed. With individual organ time activity curves biodistribution of the radiotracer were assessed, and these data were utilized for a calculation of radiation dosimetry.

Results All PET images were acquired until 3 hours after injection clearly. The uptake of blood was reached 0.1 % of injected dose at the time point of 3 min and decreased bi-exponentially. Rapid accumulation in the liver and kidneys followed by influx of activity into the intestine and the urinary bladder indicated both of them were predominant elimination organs of this radiotracer, in contrast to relatively lower uptake organs (lung, area of head and neck, muscle and other soft tissue). In dosimetry analysis, total body would be received 2.48 mSv from the administration of 370 MBq of [¹⁸F]-FAHA as an adult human.

Conclusions [¹⁸F]-FAHA provides excellent whole body PET image with an adequate absorbed radiation dose, affecting no toxicity in acute to sub-acute phase. So, it is a clinically promising radiotracer for non-invasive PET molecular imaging