Human biodistribution and radiation dosimetry of two novel α-synuclein PET tracers, ¹⁸F-SPAL-T-06 and ¹⁸F-C05-05

¹⁸F-SPAL-T-06 and ¹⁸F-C05-05 are two novel positron emission tomography (PET) radioligands targeting α-synuclein fibrils. Our study aimed to evaluate the biodistribution, safety, and radiation dosimetry of each tracer in humans. Biodistribution and radiation dosimetry studies were carried out with two healthy volunteers for each tracer, ¹⁸F-SPAL-T-06 (one female and one male volunteer, both aged 63 years) and ¹⁸F-C05-05 (one female and one male volunteer, aged 63 and 73 years, respectively). After injection of either tracer, dynamic PET images were acquired from head to upper thigh. Effective dose of each tracer was estimated using OLINDA/EXM Version 2.2. Injection of either of the tracers caused no adverse effects. Greatest uptake of both tracers was observed in the liver and small intestine. The estimated absorbed doses were highest in the biliary tract, followed by the lower large intestinal wall. Effective doses were 35.9 µSv/MBq for ¹⁸F-SPAL-T-06 and 30.5 µSv/MBq for ¹⁸F-C05-05. ¹⁸F-SPAL-T-06 and ¹⁸F-C05-05 are safe for in vivo PET imaging of humans. Their mean effective doses were 6.6 mSv for ¹⁸F-SPAL-T-06 and 5.6 mSv for ¹⁸F-C05-05 when 185 MBq of either tracer was given to a subject, and they were comparable to other amyloid and tau PET tracers labelled with ¹⁸F. Trial registration Trial registration number: jRCTs031210180, Registered date: 2nd July 2021 (¹⁸F-SPAL-T-06) https://jrct.niph.go.jp/en-latest-detail/jRCTs031210180 and Trial registration number: jRCTs031220123, Registered date: 9th June 2022 (¹⁸F-C05-05) https://jrct.niph.go.jp/en-latest-detail/jRCTs031220123.