Synthesis of 124I-iodometomidate and in vivo kinetics by small-animal PET

Objectives Halogenated derivatives of metomidate (MTO) bind with high affinity on P-450c11 receptor sites in the adrenal cortex. Labeling with I-124 was facilitated by using a stannylated precursor. Product formulation was optimized to avoid deiodination, which had been observed initially. In vivo performance of ¹²⁴I-IMTO was studied in rats by dynamic microPET recording of organ uptake and distribution kinetics.

Methods Radiosynthesis was performed by oxidative radioiododestannylation of Me₃Sn-MTO. The labeled product was isolated by reversed phase HPLC. Ascorbic acid was added to the ¹²⁴I-IMTO eluate prior to solvent evaporation. In vitro stability tests demonstrated an effect of ascorbic acid and pH. Previously, ascorbic acid alone showed no stabilizing effect. ¹²⁴I-IMTO was evaluated in rats by dynamic recording in the microPET F-220 scanner, presenting time-activity profiles of the adrenals, the liver, and kidneys. Uptake in excised organs was measured at the end of dynamic imaging.

Results ¹²⁴I-IMTO is produced in high radiochemical yields > 96% and radiochemical purity > 99% , with specific activities of ~ 80 MBq/nmol. The ¹²⁴I-IMTO injection solution is stable for at least 48 h in acetate-buffered saline. MicroPET studies indicated specific adrenal uptake reaching a stable plateau that lasted for hours. Selective adrenal uptake (5.0 ± 0.4% ID/g) was confirmed by biodistribution studies.

Conclusions ¹²⁴I-IMTO meets the requirements of high specific activity, in vitro stability, and organ selectivity. High adrenal accumulation of the radiotracer reaching steady-state conditions are excellent in vivo characteristics for adrenal imaging with PET and PET/CT.