Survey by the French Medicine Agency (ANSM) of the imaging protocol, detection rate, and safety of 68Ga-PSMA-11 PET/CT in the biochemical recurrence of prostate cancer in case of negative or equivocal 18F-fluorocholine PET/CT: 1084 examinations.

INTRODUCTION: Despite growing evidence of a superior diagnostic performance of 68Ga-PSMA-11 over 18F-fluorocholine (FCH) PET/CT, the number of PET/CT centres able to label on site with gallium-68 is still currently limited. Therefore, patients with biochemical recurrence (BCR) of prostate cancer frequently undergo FCH as the 1st-line PET/CT. Actually, the positivity rate (PR) of a second-line PSMA-11 PET/CT in case of negative FCH PET/CT has only been reported in few short series, in a total of 185 patients. Our aims were to check (1) whether the excellent PR reported with PSMA-11 is also obtained in BCR patients whose recent FCH PET/CT was negative or equivocal; (2) in which biochemical and clinical context a high PSMA-11 PET/CT PR may be expected in those patients, in particular revealing an oligometastatic pattern; (3) whether among the various imaging protocols for PSMA-11 PET/CT used in France, one yields a significantly highest PR; (4) the tolerance of PSMA-11. PATIENTS AND METHODS: Six centres performed 68Ga-PSMA-11 PET/CTs during the first 3 years of its use in France. Prior to each PET/CT, the patient's data were submitted prospectively for authorisation to ANSM, the French Medicine Agency. The on-site readings of 1084 PSMA-11 PET/CTs in BCR patients whose recent FCH PET/CTs resulted negative or equivocal were pooled and analysed. RESULTS: (1) The overall PR was 68%; for a median serum PSA level (sPSA) of 1.7 ng/mL, an oligometastatic pattern (1-3 foci) was observed in 31% of the cases overall; (2) PR was significantly related to sPSA (from 41% if < 0.2 ng/mL to 81% if ≥ 2 ng/mL), to patients' age, to initial therapy (64% if prostatectomy vs. 85% without prostatectomy due to frequent foci in the prostate fossa), to whether FCH PET/CT was negative or equivocal (PR = 62% vs. 82%), and to previous BCR (PR = 63% for 1st BCR vs. 72% in case of previous BCR); (3) no significant difference in PR was found according to the imaging protocol: injected activity, administration of a contrast agent and/or of furosemide, dose length product, one single or multiple time points of image acquisition; (4) no adverse event was reported after PSMA-11 injection, even associated with a contrast agent and/or furosemide. CONCLUSION: Compared with the performance of PSMA-11 PET/CT in BCR reported independently of FCH PET/CT in 6 large published series (n > 200), the selection based on FCH PET/CT resulted in no difference of PSMA-11 PR for sPSA < 1 ng/mL but in a slightly lower PR for sPSA ≥ 1 ng/mL, probably because FCH performs rather well at this sPSA and very occult BCR was over-represented in our cohort. An oligometastatic pattern paving the way to targeted therapy was observed in one fourth to one third of the cases, according to the clinico-biochemical context of the BCR. Systematic dual or triple acquisition time points or administration of a contrast agent and/or furosemide did not bring a significant added value for PSMA-11 PET/CT positivity and should be decided on individual bases.

Current evaluation of the clinical utility of Fluoromethylcholine-(18F) PET/CT in Prostate Cancer

This short review is dedicated to the current status of the assessment of a new PET radiopharmaceutical, fluoromethylcholine-(18F) or FCH, which is taken-up by prostate cancer tissue, in contrary to fluorodeoxyglucose-(18F) or FDG. It seems that FCH could become "the FDG of prostate cancer", with the same type of achievements (detection of distant metastases and of occult recurrences, restaging prior to invasive treatments), and the same drawbacks (false negative results in case of small lesions, in particular lymph nodes metastases, and false positive results in case of infection/inflammation, in particular prostatitis). Current evidence is summarised and discussed for each of the potential settings of FCH PET/CT imaging in prostate cancer. The perspectives for granting a marketing authorisation to a FCH preparation are briefly analysed.

Esta breve revisão é dedicada ao estado atual da avaliação de um novo radiofármaco PET, a fluormetilcolina-(18F) ou FCH, que é captada pelo tecido do câncer de próstata, ao contrário da fluordesoxiglicose-(18F) ou FDG. Parece que a FCH poderia se tornar "a FDG do câncer de próstata", com o mesmo tipo de funções (detecção de metástases distantes e de recorrências ocultas, antes de tratamentos invasivos), e os mesmos inconvenientes (falso resultado negativo no caso de pequenas lesões, em especial das metástase de nodos linfáticos, e de falsos resultados positivos em caso de infecção/inflamação, em particular prostatite). Evidência atual é resumida e discutida para cada uma das definições potenciais da imagem FCH PET/CT em câncer de próstata. As perspectivas para a concessão de uma autorização de comercialização para uma preparação de FCH são analisadas brevemente.

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

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.

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.