Dosimetry in nonhuman primates of [18F]LMI1195, a novel PET tracer for imaging the cardiac sympathetic nervous system

Objectives LMI1195, labeled with 18F is under clinical development as a novel norepinephrine transporter (NET) ligand, which is potentially a useful radiotracer for mapping the cardiac nerve terminals in vivo. For an appropriate phase I clinical trial dose, a study was performed in non-human primates to estimate human radiation dosimetry. Methods Two male and two female cynomolgus monkeys were imaged using a MicroPET scanner for whole body 18F distribution following 4 to 5 mCi (0.65 to 1.6 μg) single intravenous injection of [18F]LMI1195. Images from head to lower abdomen were acquired over four and half hours following injection. Radioactivity in identifiable organs and the remainder of the body was determined using region-of-interest analysis. The total number of disintegrations was determined by normalizing the injected radioactivity. Using OLINDA/EXM software, the normalized number of 18F disintegrations for each organ was combined with the energy released by each disintegration and, using the MIRD schema, estimates were made for the fraction retention of energy that would be in the source organ and the contribution to surrounding organs for an adult human. Results From the radiation dose estimates, the human organ that would receive the highest dose was the urinary bladder wall with an average of 0.41 ± 0.089 rem/mCi. The next five highest dose organs and their respective mean dose estimates were the kidneys (0.15 ± 0.088 rem/mCi), adrenals (0.14 ± 0.027 rem/mCi), heart wall (0.085 ± 0.014 rem/mCi), osteogenic cells (0.084 ± 0.0048 rem/mCi), and red bone marrow (0.083 ± 0.0099 rem/mCi). The mean whole body dose estimate was 0.044 ± 0.00031 rem/mCi and the mean effective dose as defined in ICRP 60 was 0.070 ± 0.0059 rem/mCi. Conclusions Based on average values, the maximum dose of [18F]LMI1195 that may be administered to a human without exceeding 50 mSv (5 rem) to the urinary bladder was estimated to be 12 mCi. Similarly, the maximum administered dose that does not exceed 10 mSv effective dose was estimated to be 14 mCi.