Biodistribution and Radiation Dosimetry of ¹⁸F-FTC-146 in Humans

Abstract

The purpose of this study was to assess safety, biodistribution, and radiation dosimetry in humans for the highly selective σ-1 receptor PET agent F-6-(3-fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo[]thiazol-2(3H)-one (F-FTC-146). Ten healthy volunteers (5 women, 5 men; age ± SD, 34.3 ± 6.5 y) were recruited, and written informed consent was obtained from all participants. Series of whole-body PET/MRI examinations were acquired for up to 3 h after injection (357.2 ± 48.8 MBq). Blood samples were collected, and standard vital signs (heart rate, pulse oximetry, and body temperature) were monitored at regular intervals. Regions of interest were delineated, time-activity curves were calculated, and organ uptake and dosimetry were estimated. All subjects tolerated the PET/MRI examination well, and no adverse reactions to F-FTC-146 were reported. High accumulation ofF-FTC-146 was observed in σ-1 receptor-dense organs such as the pancreas and spleen, moderate uptake in the brain and myocardium, and low uptake in bone and muscle. High uptake was also observed in the kidneys and bladder, indicating renal tracer clearance. The effective dose of F-FTC-146 was 0.0259 ± 0.0034 mSv/MBq (range, 0.0215-0.0301 mSv/MBq). First-in-human studies with clinical-grade F-FTC-146 were successful. Injection ofF-FTC-146 is safe, and absorbed doses are acceptable. The potential of F-FTC-146 as an imaging agent for a variety of neuroinflammatory diseases is currently under investigation.

Applications of PET‐MRI in musculoskeletal disease

“…An in vivo animal study showed the increased uptake of 18F‐FTC‐146 at the site of nerve injury, demonstrating its feasibility as a neuropathic pain marker. The biodistribution and radiation dosimetry of 18F‐FTC‐146 in human controls were presented to validate its safety and stability for PET‐MRI on human subjects . The recent application of 18F‐FTC‐146 PET‐MRI to patients with complex regional pain syndrome showed that the imaging findings altered the pain management plan for 7 of 8 patients, and change of therapy in two patients achieved a considerably improved pain‐relief outcome…”

“…The biodistribution and radiation dosimetry of 18F-FTC-146 in human controls were presented to validate its safety and stability for PET-MRI on human subjects. 134 The recent application of 18F-FTC-146 PET-MRI to patients with complex regional pain syndrome showed that the imaging findings altered the pain management plan for 7 of 8 patients, and change of therapy in two patients achieved a considerably improved pain-relief outcome. 135 In conclusion, PET-MRI for neuropathic pain has demonstrated promising results in detection of causative nerve damage, which has altered pain management and achieved better patient outcomes.…”

18F‐Labeled benzylpiperazine derivatives as highly selective ligands for imaging σ1 receptor with positron emission tomography

“…Many potential radiotracers for imaging σ 1 receptors with positron emission tomography (PET) have been reported . However, only [ 11 C]SA4503, [ 18 F]FPS, [ 18 F]FTC‐146, and ( S )‐[ 18 F]fluspidine have been evaluated in humans. In vivo [ 11 C]SA4503 imaging studies have shown that the density of σ 1 receptors was decreased in patients with Parkinson's disease (PD) and Alzheimer's disease (AD) .…”

“…Because of the short half‐life of 11 C, production of [ 11 C]SA4503 requires an on‐site cyclotron and thus limits its use. Among the three 18 F‐labeled compounds, [ 18 F]FPS 13 and [ 18 F]FTC‐146 show very slow kinetics in the human brain and are not suitable for neuroimaging of σ 1 receptors. ( S )‐[ 18 F]fluspidine is another promising radiotracer, which is currently used to image the σ 1 receptors in patients with major depressive disorders and Huntington´s disease .…”

Nuclear Medicine Procedures in Women: Unappreciated Risks to Reproductive Organs?

“…While it can be argued that the risks of diagnostic nuclear medicine procedures using relatively short-lived isotopes could be viewed as mostly hypothetical (8), this is definitely not the case for radiopharmaceuticals in use and under development for targeted radionuclide therapy, which use high-energy nuclides with longer half-life (19) and are specifically designed to inflict direct cell damage. Despite this, the most recent dosimetry studies for new diagnostic and therapeutic radiopharmaceuticals, even when including both sexes, do not report organ exposure separately for men and women and do not mention hormonal status (pre-vs postmenopausal) or stage of the menstrual cycle on the day of imaging (32)(33)(34)(35). To elaborate, targeted radionuclide therapy development may involve the use of "theranostic" agents, whereby a pair of radiopharmaceuticals targeting the same molecule are used to assess biodistribution and "personalized" dosimetry with a low energy, short half-life isotope and achieve tumor response with a higher-energy emitter (3,19).…”