Preclinical dose assessment and comparison of (S)-(-)-[¹⁸F]fluspidine and (R)-(+)-[¹⁸F]fluspidine, new stereoisomeric PET tracers for imaging of σ₁ receptors

Ziel: [¹⁸F]Fluspidine (FPD) is a new radio-ligand for imaging of σ₁ receptors, a unique type of chaperone which is connected to cancer and neuropsychiatric diseases. To assess the radiation risk to humans, CD1 mice were injected with (S)-(-)-FPD# and (R)-(+)-FPD##. The biodistribution, the organ doses (OD) and effective dose (ED) were estimated.

Methodik: 28#/22## female CD1 mice (weight: 29.8±2.2g#/29.3±1.9g##) were i.v. injected with 0.35±0.08 MBq#/0.39±0.05 MBq## FPD through the V. caudata lateralis. At 5, 15, 30, 45, 60, 90, 120, 180 and 240 min. p.i. the animals were sacrificed (2-4 per time). The organs were isolated, weighed and counted in a γ-counter to determine mass and radioactivity. The masses of skeleton and muscle were extrapolated. The fractions of activity in the source organs were displayed as %ID and scaled to the human magnitude. Time-activity curves were derived by exponential fitting. The numbers of disintegrations in the source organs were calculated as well the ODs and the ED using OLINDA.

Ergebnisse: For (S)-(-)-FPD# the adrenals receive the highest OD (36.0 µSv/MBq), followed by the kidneys (35.6 µSv/MBq) and upper large intestine (ULI) (33.3 µSv/MBq). The highest contribution to the ED was by lungs (3.7µSv/MBq) and ULI (2.0µSv/MBq). For (R)-(+)-FPD## the lungs receive the highest OD (45.5 µSv/MBq), followed by the kidneys (27.6 µSv/MBq) and ULI (25.6 µSv/MBq). The highest contribution to the ED was by lungs (5.5µSv/MBq) followed by ovaries (2.0µSv/MBq). According to these data, the EDs result in 16.7#/18.4## µSv/MBq.

Schlussfolgerungen: Due to this data, the EDs to humans upon i.v. application of 300 MBq would be 8.4mSv#/9.2mSv##, taking into account that preclinical dosimetry usually underestimates the ED to humans up to 40%. This is within the range of what is caused by other [F18]-labeled compounds. This risk assessment encourages to transfer FPD from preclinical to clinical study phases and to further develop it as a clinical tool for brain and cancer-PET imaging.