Dataset Information

Rapid Aqueous Late-Stage Radiolabelling of [GaF₃ (BnMe₂ -tacn)] by ¹⁸ F/¹⁹ F Isotopic Exchange: Towards New PET Imaging Probes.

ABSTRACT: A simple and rapid method for ¹⁸ F radiolabelling of [GaF₃ (BnMe₂ -tacn)] by ¹⁸ F/¹⁹ F isotopic exchange is described. The use of MeCN/H₂ O or EtOH/H₂ O (75:25) and aqueous [¹⁸ F]F^- (up to 200?MBq) with heating (80?°C, 10?min) gave 66±4?% ¹⁸ F incorporation at a concentration of 268?nm, and 37±5?% ¹⁸ F incorporation at even lower concentration (27?nm), without the need for a Lewis acid promoter. A solid-phase extraction method was established to give [Ga¹⁸ F¹⁹ F₂ (BnMe₂ -tacn)] in 99?% radiochemical purity in an EtOH/H₂ O mixture.

SUBMITTER: Monzittu FM

PROVIDER: S-EPMC6055623 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Publications

Rapid Aqueous Late-Stage Radiolabelling of [GaF3 (BnMe2 -tacn)] by 18 F/19 F Isotopic Exchange: Towards New PET Imaging Probes.

Monzittu Francesco M FM Khan Imtiaz I Levason William W Luthra Sajinder K SK McRobbie Graeme G Reid Gillian G

Angewandte Chemie (International ed. in English) 20180426 22

A simple and rapid method for 18 F radiolabelling of [GaF3 (BnMe2 -tacn)] by 18 F/19 F isotopic exchange is described. The use of MeCN/H2 O or EtOH/H2 O (75:25) and aqueous [18 F]F- (up to 200 MBq) with heating (80 °C, 10 min) gave 66±4 % 18 F incorporation at a concentration of 268 nm, and 37±5 % 18 F incorporation at even lower concentration (27 nm), without the need for a L ...[more]

PMID: 29659110

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Project description:BackgroundBoth enantiomers of [18F]flubatine are new radioligands for neuroimaging of α4β2 nicotinic acetylcholine receptors with positron emission tomography (PET) exhibiting promising pharmacokinetics which makes them attractive for different clinical questions. In a previous preclinical study, the main advantage of (+)-[18F]flubatine compared to (-)-[18F]flubatine was its higher binding affinity suggesting that (+)-[18F]flubatine might be able to detect also slight reductions of α4β2 nAChRs and could be more sensitive than (-)-[18F]flubatine in early stages of Alzheimer's disease. To support the clinical translation, we investigated a fully image-based internal dosimetry approach for (+)-[18F]flubatine, comparing mouse data collected on a preclinical PET/MRI system to piglet and first-in-human data acquired on a clinical PET/CT system. Time-activity curves (TACs) were obtained from the three species, the animal data extrapolated to human scale, exponentially fitted and the organ doses (OD), and effective dose (ED) calculated with OLINDA.ResultsThe excreting organs (urinary bladder, kidneys, and liver) receive the highest organ doses in all species. Hence, a renal/hepatobiliary excretion pathway can be assumed. In addition, the ED conversion factors of 12.1 μSv/MBq (mice), 14.3 μSv/MBq (piglets), and 23.0 μSv/MBq (humans) were calculated which are well within the order of magnitude as known from other 18F-labeled radiotracers.ConclusionsAlthough both enantiomers of [18F]flubatine exhibit different binding kinetics in the brain due to the respective affinities, the effective dose revealed no enantiomer-specific differences among the investigated species. The preclinical dosimetry and biodistribution of (+)-[18F]flubatine was shown and the feasibility of a dose assessment based on image data acquired on a small animal PET/MR and a clinical PET/CT was demonstrated. Additionally, the first-in-human study confirmed the tolerability of the radiation risk of (+)-[18F]flubatine imaging which is well within the range as caused by other 18F-labeled tracers. However, as shown in previous studies, the ED in humans is underestimated by up to 50 % using preclinical imaging for internal dosimetry. This fact needs to be considered when applying for first-in-human studies based on preclinical biokinetic data scaled to human anatomy.

Project description:BackgroundDopamine transporter (DAT) imaging is used in the diagnostic work-up in suspected parkinsonian syndromes and dementia with Lewy bodies but cannot differentiate between these syndromes, and an extra brain imaging examination of the regional cerebral blood flow (rCBF) or glucose metabolism is often needed for differential diagnosis. The requirement of two different imaging examinations is resource-consuming and inconvenient for the patients. Therefore, imaging of both cortical blood flow and DAT imaging with the same radiotracer would be more convenient and cost-effective. The aim of this study was to test whether relative regional cerebral blood flow (rCBFR) can be measured with the DAT-specific positron emission tomography (PET) tracer [18F]FE-PE2I (FE-PE2I), by validation with cerebral perfusion measured with [15O]H2O PET (H2O).MethodsThe rCBFR was quantified by kinetic modeling for FE-PE2I (R1) and H2O (F). The R1 was calculated using the simplified reference tissue model, and F was calculated with a modified Koopman double-integration method. The linear relationship and intraclass correlation (ICC) between R1 and F were tested in image data derived from 29 patients with recent onset parkinsonism and 30 healthy controls.ResultsThere was a strong linear correlation across all subjects between R1 and F in the frontal, parietal, temporal, cingulate and occipital cortex as well as in the striatum (r ≥ 0.731-0.905, p < 0.001) with a good-to-excellent ICC, ranging from 0.727 to 0.943 (p < 0.001).ConclusionsOur results suggest that FE-PE2I may be used as a proxy for cerebral perfusion, thus potentially serving as a radiotracer for assessment of both DAT availability and rCBFR in one single dynamic scan. This could be valuable in the differential diagnosis of parkinsonian syndromes.Trial registrationEUDRA-CT 2015-003045-26. Registered 23 October 2015 https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-003045-26.

Dataset Information

Rapid Aqueous Late-Stage Radiolabelling of [GaF₃ (BnMe₂ -tacn)] by ¹⁸ F/¹⁹ F Isotopic Exchange: Towards New PET Imaging Probes.

Publications

Rapid Aqueous Late-Stage Radiolabelling of [GaF<sub>3</sub> (BnMe<sub>2</sub> -tacn)] by <sup>18</sup> F/<sup>19</sup> F Isotopic Exchange: Towards New PET Imaging Probes.

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