Mickael Huiban

Clinical Translation of a ‘Click’ Labeled 18F-Octreotate Radioligand for Imaging Neuroendocrine Tumors

We conducted the first-in-human study of 18F-fluoroethyl triazole [Tyr3] octreotate (18F-FET-βAG-TOCA) in patients with neuroendocrine tumors (NETs) to evaluate biodistribution, dosimetry, and safety. Despite advances in clinical imaging, detection and quantification of NET activity remains a challenge, with no universally accepted imaging standard. Methods: Nine patients were enrolled. Eight patients had sporadic NETs, and 1 had multiple endocrine neoplasia type 1 syndrome. Patients received 137–163 MBq (mean ± SD, 155.7 ± 8 MBq) of 18F-FET-βAG-TOCA. Safety data were obtained during and 24 h after radioligand administration. Patients underwent detailed whole-body PET/CT multibed scanning over 4 h with sampling of venous bloods for radioactivity and radioactive metabolite quantification. Regions of interest were defined to derive individual and mean organ residence times; effective dose was calculated with OLINDA 1.1. Results: All patients tolerated 18F-FET-βAG-TOCA with no adverse events. Over 60% parent radioligand was present in plasma at 60 min. High tumor (primary and metastases)-to-background contrast images were observed. Physiologic distribution was seen in the pituitary, salivary glands, thyroid, and spleen, with low background distribution in the liver, an organ in which metastases commonly occur. The organs receiving highest absorbed dose were the gallbladder, spleen, stomach, liver, kidneys, and bladder. The calculated effective dose over all subjects (mean ± SD) was 0.029 ± 0.004 mSv/MBq. Conclusion: The favorable safety, imaging, and dosimetric profile makes 18F-FET-βAG-TOCA a promising candidate radioligand for staging and management of NETs. Clinical studies in an expanded cohort are ongoing to clinically qualify this agent.

Use of LC-MS for the quality control of radiopharmaceuticals: example of [18F]ML10

[(18)F]ML10 is a promising novel low molecular weight positron emission tomography probe for apoptosis. As part of the quality control to support clinical studies for cancer therapy monitoring in the GSK Clinical Imaging Centre, a simple and sensitive liquid chromatography mass spectrometry method has been developed and validated for the quantification of total ML10 and impurity content in the final product. Chromatographic separation of ML10 and its radiolabelling precursor and impurities was achieved. Mass curves were constructed from a concentration range of ML10 and known impurities and were linear. Quantification was achieved by comparison of the area under the curve for ML10 content (m/z = 205) and the mass curve. The method was validated over a concentration range of 0.1-1 µg/ml.

Within-subject comparison of the sensitivity of [11C]-(+)-PHNO and [11C]raclopride to amphetamine induced changes in endogenous dopamine in healthy human volunteers

Background: Benzamide antagonist radioligands for the D2/3 receptor (D2/3R), such as [C]raclopride or [I]IBZM, have been used to index fluctuations in endogenous dopamine (DA) in the brain. The sensitivity of this technique is limited; large increases in extracellular DA are associated with relatively small changes in ligand binding (∼10–15% in healthy human volunteers). Theoretical considerations indicate that agonist radioligands may be more sensitive to detect fluctuations in brain dopamine. [C]-(+)-PHNO is an agonist radioligand with ∼20-fold higher affinity for the D3R than D2R [1]. This study compared the sensitivity of [C]-(+)-PHNO to detect changes in endogenous dopamine to that of [C]raclopride, using a within-subject design.