Whole-body biodistribution and radiation dosimetry of [18F]PR04.MZ: a new PET radiotracer for clinical management of patients with movement disorders

Lehnert, Wencke; Riss, Patrick J.; Mendoza, Ana Hurtado de; López, Sandra; Fernández, Gonzalo Gutiérrez; Ilheu, Marcelo; Amaral, Horacio; Kramer, Vasko

doi:10.1186/s13550-021-00873-9

Cited by 8 publications

(5 citation statements)

References 21 publications

(41 reference statements)

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“…Since [ 18 F]FP-CIT and [ 123 I]FP-CIT are radiopharmaceuticals employed in clinical applications, radiation dosimetry in humans has already been established. The clinical outcomes of [ 18 F]FP-CIT indicate a shorter residence time, reduced radiation absorbed dose, and lower effective dose equivalent compared with those of [ 123 I]FP-CIT [ 29 , 39 – 43 ]. The diminished radiation exposure of [ 18 F]FP-CIT is attributed to a composite of the following three inherent properties: (1) the short half-life of 18 F, (2) the prompt clearance of [ 18 F]FP-CIT, and (3) the formation of non-radioactive metabolites that differ from those of [ 123 I]FP-CIT.…”

Section: Discussionmentioning

confidence: 99%

Preclinical evaluation of [18F]FP-CIT, the radiotracer targeting dopamine transporter for diagnosing Parkinson’s disease: pharmacokinetic and efficacy analysis

Ahn,

Kim,

Lee

et al. 2024

EJNMMI Res

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Background N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (FP-CIT), the representative cocaine derivative used in dopamine transporter imaging, is a promising biomarker, as it reflects the severity of Parkinson’s disease (PD). 123I- and 18F-labeled FP-CIT has been used for PD diagnosis. However, preclinical studies evaluating [18F]FP-CIT as a potential diagnostic biomarker are scarce. Among translational research advancements from bench to bedside, translating preclinical findings into clinical practice is one-directional. The aim of this study is to employ a circular approach, beginning back from the preclinical stage, progressing to the supplementation of [18F]FP-CIT, and subsequently returning to clinical application. We investigated the pharmacokinetic properties of [18F]FP-CIT and its efficacy for PD diagnosis using murine models. Results Biodistribution, metabolite and excretion analyses were performed in mice and PD models were induced in rats using 6-hydroxydopamine (6-OHDA). The targeting efficiency of [18F]FP-CIT for the dopamine receptor was assessed through animal PET/CT imaging. Subsequently, correlation analysis was conducted between animal PET/CT imaging results and immunohistochemistry (IHC) targeting tyrosine hydroxylase. Rapid circulation was confirmed after [18F]FP-CIT injection. [18F]FP-CIT reached the highest uptake of 23.50 ± 12.46%ID/g in the striatum 1 min after injection, and it was rapidly excreted within 60 min. The major metabolic organs of [18F]FP-CIT were confirmed to be the intestines, liver, and kidneys. Its uptake in the intestine was approximately 5% ID/g. The uptake in the liver gradually increased, with excretion beginning after reaching a maximum after 60 min. The kidneys exhibited rapid elimination after 10 min. In the excretion study, rapid elimination was verified, with 21.46 ± 9.53% of the compound excreted within a 6 h period. Additionally, the efficacy of [18F]FP-CIT PET was demonstrated in the PD model, with a high correlation with IHC for both the absolute value (R = 0.803, p = 0.0017) and the ratio value (R = 0.973, p = 0.0011). Conclusions This study fills the gap regarding insufficient preclinical studies on [18F]FP-CIT, including its ADME, metabolites, and efficiency. The pharmacological results, including accurate diagnosis, rapid circulation, and [18F]FP-CIT excretion, provide complementary evidence that [18F]FP-CIT can be used safely and efficiently to diagnose PD in clinics, although it is already used in clinics.

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Section: Discussionmentioning

confidence: 99%

Preclinical evaluation of [18F]FP-CIT, the radiotracer targeting dopamine transporter for diagnosing Parkinson’s disease: pharmacokinetic and efficacy analysis

Ahn,

Kim,

Lee

et al. 2024

EJNMMI Res

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“…PET imaging of DAT is a useful diagnostic method for tracking dopaminergic neurodegeneration in the striatum and ventral area of the SNpc in movement disorders [1][2][3]. Previous studies demonstrated that PET imaging with [ 18 F]PR04.MZ provides an excellent image quality with high sensitivity for evaluation of patients with movement disorders [37][38][39][40][41][42].…”

Section: Discussionmentioning

confidence: 99%

“…The reduction of presynaptic biomarkers, such as dopamine transporters (DAT), indicates the loss of nigrostriatal neurons and the subsequent dopaminergic de cit in the striatal regions of the brain. [ 18 F]PR04.MZ is a PET tracer with high a nity, selectivity, and speci city for DAT, suitable for detecting dopaminergic de cit in the striatum and SNpc even before any motor symptoms appear [37][38][39][40][41][42].…”

Section: Introductionmentioning

confidence: 99%

Image-based machine learning model as a tool for classification of [ 18 F]PR04.MZ PET images in patients with parkinsonian syndrome

Jiménez,

Soza-Ried,

Kramer

et al. 2023

Preprint

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Parkinsonian syndrome (PS) is characterized by bradykinesia, resting tremor, and rigidity, and it represents the phenotype observed in various neurodegenerative disorders. Positron emission tomography (PET) imaging plays an important role in diagnosing PS by detecting the progressive loss of dopaminergic neurons. This study aimed to develop and compare five machine-learning models for classifying [18F]PR04.MZ PET images between patients with PS and subjects without evidence for dopaminergic deficit (SWEDD). A dataset of [18F]PR04.MZ PET images from 204 subjects was analyzed and classified into PS compatible (1) and SWEDDs (0) by three blinded expert readers. The images were preprocessed to generate two and three-dimensional datasets. Five different pattern recognition algorithms, commonly used for image analysis, were trained and validated, comparing their performance to the majority reading of expert diagnosis considered as the standard of truth. Three models outperformed the others, achieving an accuracy greater than 98%. The results demonstrated that our machine-learning models, combined with [18F]PR04.MZ PET images, provide highly accurate and precise tools to support clinicians in PET image analysis. This approach may reduce the time required for interpretation and increase certainty in the diagnostic process.

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“…Dysautonomia was evaluated using the Composite Autonomic Symptom Score (COMPASS31) scale (Sletten et al, 2012)-The RBD-13 and the RBD-1Q screening questionnaires were answered by participants or caretakers living with them (Postuma, Arnulf, et al, 2012;Stiasny-Kolster et al, 2007). Integrity of dopaminergic neurons in nigrostriatal regions was evaluated by PET/CT imaging of DAT with 18 F-PR04.MZ, as previously described (Juri et al, 2021;Kramer et al, 2020;Lehnert et al, 2022).…”

Section: Methodsmentioning

confidence: 99%

Prodromal manifestations of Parkinson’s disease in adults with 22q11.2 microdeletion syndrome

Juri

Chaná-Cuevas

Kramer

et al. 2022

Preprint

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Abstract22q11.2 microdeletion syndrome (22qDS) was recently identified as a risk factor for development of early-onset Parkinson’s disease (PD). The classical motor manifestations of this disease are preceded by early signs and symptoms of neurodegeneration. The progression of 22qDS-associated PD is unknown. We aimed to evaluate the presence of prodromal PD in a group of adults with 22qDS using the Movement Disorders Society (MDS) Criteria for Prodromal PD. Thirty-eight persons with 22qDS and 13 age-matched controls participated in the study, and their results were compared using the Mann-Whitney U test. Persons with 22qDS had lower scores on olfaction testing (p=7.42E×10−5), higher scores on the COMPASS 31 scale for dysautonomia (p=2.28×10−3) and on the motor evaluation using Movement Disorder Society (MDS)-sponsored revision of Unified Parkinson’s Disease Rating Scale motor subscore (UPDRS-III) (p=1.84×10−4), compared with healthy controls. Home polysomnogram did not find participants with REM-sleep behavior disorder. Integrity of nigrostriatal dopaminergic system was evaluated by PET-CT imaging of presynaptic dopamine with 18F-PR04.MZ. Patients showed significantly higher specific binding ratios in the striatum, compared to controls (p=9.57×10−3 at the caudate nuclei). Two patients with 22qDS (5.2%) had decreased uptake in the posterior putamen (less than 60% of controls) and one fulfilled MDS criteria for prodromal PD. These results show that patients with 22qDS manifest some signs and symptoms of prodromal PD such as hyposmia, dysautonomia and mild movement alterations. In the majority, this was associated with elevated dopaminergic signaling, suggesting that loss of dopaminergic neurons may not be the cause. A smaller subgroup did show evidence of a decrease in nigrostriatal dopaminergic signaling, as seen in classical prodromal PD. Longitudinal studies are necessary to understand the progression to and risk of PD in persons with 22qDS.

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Whole-body biodistribution and radiation dosimetry of [18F]PR04.MZ: a new PET radiotracer for clinical management of patients with movement disorders

Cited by 8 publications

References 21 publications

Preclinical evaluation of [18F]FP-CIT, the radiotracer targeting dopamine transporter for diagnosing Parkinson’s disease: pharmacokinetic and efficacy analysis

Preclinical evaluation of [18F]FP-CIT, the radiotracer targeting dopamine transporter for diagnosing Parkinson’s disease: pharmacokinetic and efficacy analysis

Image-based machine learning model as a tool for classification of [ 18 F]PR04.MZ PET images in patients with parkinsonian syndrome

Prodromal manifestations of Parkinson’s disease in adults with 22q11.2 microdeletion syndrome

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