INTRODUCTION: A new radiotracer for imaging the serotonin 4 receptors (5-HT4) in brain, [¹⁸F]MNI-698, was recently developed by our group. Evaluation in nonhuman primates indicates the novel radiotracer holds promise as an imaging agent of 5-HT4 in brain. This paper aims to describe the whole-body biodistribution and dosimetry estimates of [¹⁸F]MNI-698. METHODS: Whole-body positron emission tomography (PET) images were acquired over 240 minutes after intravenous bolus injection of [¹⁸F]MNI-698 in adult rhesus monkeys. Different models were investigated for quantification of radiation absorbed and effective doses using OLINDA/EXM 1.0 software. RESULTS: The radiotracer main elimination route was found to be urinary and the critical organ was the urinary bladder. Modeling of the urinary bladder voiding interval had a considerable effect on the estimated effective dose. Normalization of rhesus monkeys' organs and whole-body masses to human equivalent reduced the calculated dosimetry values. The effective dose ranged between 0.017 and 0.027 mSv/MBq. CONCLUSION: The dosimetry estimates, obtained when normalizing organ and whole-body weights and applying the urinary bladder model, indicate that the radiation doses from [¹⁸F]MNI-698 comply with limits and guidelines recommended by key regulatory authorities that govern the translation of radiotracers to human clinical trials. The timing of urinary bladder emptying should be considered when designing future clinical protocols with [¹⁸F]MNI-698, in order to minimize the subject absorbed doses.
INTRODUCTION: A new radiotracer for imaging the serotonin 4 receptors (5-HT4) in brain, [¹⁸F]MNI-698, was recently developed by our group. Evaluation in nonhuman primates indicates the novel radiotracer holds promise as an imaging agent of 5-HT4 in brain. This paper aims to describe the whole-body biodistribution and dosimetry estimates of [¹⁸F]MNI-698. METHODS: Whole-body positron emission tomography (PET) images were acquired over 240 minutes after intravenous bolus injection of [¹⁸F]MNI-698 in adult rhesus monkeys. Different models were investigated for quantification of radiation absorbed and effective doses using OLINDA/EXM 1.0 software. RESULTS: The radiotracer main elimination route was found to be urinary and the critical organ was the urinary bladder. Modeling of the urinary bladder voiding interval had a considerable effect on the estimated effective dose. Normalization of rhesus monkeys' organs and whole-body masses to human equivalent reduced the calculated dosimetry values. The effective dose ranged between 0.017 and 0.027 mSv/MBq. CONCLUSION: The dosimetry estimates, obtained when normalizing organ and whole-body weights and applying the urinary bladder model, indicate that the radiation doses from [¹⁸F]MNI-698 comply with limits and guidelines recommended by key regulatory authorities that govern the translation of radiotracers to human clinical trials. The timing of urinary bladder emptying should be considered when designing future clinical protocols with [¹⁸F]MNI-698, in order to minimize the subject absorbed doses.
Authors: Adam A Garrow; Jack P M Andrews; Zaniah N Gonzalez; Carlos A Corral; Christophe Portal; Timaeus E F Morgan; Tashfeen Walton; Ian Wilson; David E Newby; Christophe Lucatelli; Adriana A S Tavares Journal: Sci Rep Date: 2020-09-29 Impact factor: 4.379
Authors: Mark G MacAskill; Agne Stadulyte; Lewis Williams; Timaeus E F Morgan; Nikki L Sloan; Carlos J Alcaide-Corral; Tashfeen Walton; Catriona Wimberley; Chris-Anne McKenzie; Nick Spath; William Mungall; Ralph BouHaidar; Marc R Dweck; Gillian A Gray; David E Newby; Christophe Lucatelli; Andrew Sutherland; Sally L Pimlott; Adriana A S Tavares Journal: J Nucl Med Date: 2020-08-28 Impact factor: 11.082