FDOPA-(18F): a PET radiopharmaceutical recently registered for diagnostic use in countries of the European Union

Abstract

Positron emission tomography (PET) and its recent update PET/CT are very effective diagnostic tools for non-invasive imaging of metabolic or functional disorders in target tissues. The clinical usefulness of fluorodeoxyglucose-(18F) (FDG) has been now widely accepted. Recently, the clinical usefulness of fluoroDOPA-(18F) or FDOPA, an aminoacid labelled with the same positron emitter fluorine-18, has been evaluated and recognised in France and subsequently in several EU countries. FDOPA is diagnostic PET agent, which has been used for decades in imaging the loss of dopaminergic neurons in Parkinson's disease, and more recently to detect, stage and restage neuroendocrine tumours and to search for recurrence of viable glioma tissue. The present article summarises the body of evidence that led the French Medicines Agency (AFSSAPS) to grant a marketing authorisation to IASOdopa, a commercial preparation of FDOPA. Brief case reports and figures illustrate the diagnostic performance of FDOPA PET or PET/CT in the different settings that are currently approved in oncology.<br>Tomografia por emissão de positrons (PET) e sua recente atualização PET/CT são ferramentas de diagnóstico muito eficientes para imagens não invasivas de desordens metabólicas ou funcionais em tecido alvo. A utilidade clínica da fluordesoxiglicose-(18F)(FDG) tem sido agora largamente aceita. Recentemente, a utilidade clinica de fluoroDOPA-(18F) ou FDOPA, um aminoácido marcado com o mesmo emissor de pósitron, flúor-18, tem sido avaliado e reconhecido na França e subsequentemente em alguns países da União Européia. FDOPA é o radiofármaco para diagnóstico em PET, o qual tem sido usado por décadas para obtenção de imagens da perda de neurônios dopaminérgicos na doença de Parkinson e, mais recentemente, para identificar inicialmente o estágio e a reavaliação de tumores neuroendócrinos e para a pesquisa da recorrência de glioma viável. O presente artigo resume o conjunto de evidências que levarão a Agência Médica Francesa (AFSSAPS) garantir uma autorização de divulgação da IASOdopa, uma preparação comercial da FDOPA. O relato breve de caso e figuras que ilustram um padrão de imagem de diagnóstico usando FDOPA em PET ou PET/CT em diferentes configurações que são aceitas em oncologia

Use of 55 PET radiotracers under approval of a Radioactive Drug Research Committee (RDRC)

“…We do not expect clinically detectable pharmacological effects as the mass limit (≤0.14 μg/kg) has been used without significant adverse events at other institutions (see: Wong et al 2010); f Includes subjects numbers scanned for clinical care and research; g [ 18 F]FDOPA is validated for clinical production but studies have not yet commenced. We do not expect clinically detectable pharmacological effects as the mass limit (≤15 μg/subject) is significantly less than administered masses historically used when employing the electrophilic synthesis of [ 18 F]FDOPA (13 mg/62 kg subject, see: Chevalme et al 2007)…”

The role of neuroimaging in Parkinson’s disease

“…From [ 18 F]F-DOPA uptake measurements in PD patients taken at two timepoints 18 months apart, it was estimated that the average preclinical (asymptomatic) period of PD is likely no longer than 7 years (Morrish et al, 1998). [ 18 F]F-DOPA was officially approved in the EU in 2006 and in the United States in 2019 for diagnosing PD and distinguishing essential tremor from parkinsonian syndromes, that is, PD and atypical PS (Chevalme et al, 2007;NDA 200655).…”

18F-6-Fluoro-l-Dopa PET/CT Imaging of Congenital Hyperinsulinism

“…Alternatively, PET data can be fused with MRI data. 18 F-FDOPA has been registered in the European Union since November 2006 (38). A new drug application filed in the United States in 2018 is in review by the Food and Drug Administration (39) and includes the nucleophilic technique as the proposed chemistry, manufacturing and control technique.…”