Scientific Publications

January 30, 2018

A human PET study of [11C]HMS011, a potential radioligand for AMPA receptors

Keisuke Takahata1,2, Yasuyuki Kimura1,3* , Chie Seki1, Masaki Tokunaga1, Masanori Ichise1, Kazunori Kawamura4, Maiko Ono1, Soichiro Kitamura1, Manabu Kubota1, Sho Moriguchi1,5, Tatsuya Ishii1, Yuhei Takado1, Fumitoshi Niwa1,6, Hironobu Endo1,7, Tomohisa N

α-Amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor is a primary mediator of fast
glutamatergic excitatory signaling in the brain and has been implicated in diverse neuropsychiatric diseases. We
recently developed a novel positron emission tomography (PET) ligand, 2-(1-(3-([11C]methylamino)phenyl)-2-oxo-5-
(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl) benzonitrile ([11C]HMS011). This compound is a radiolabelled derivative of
perampanel, an antiepileptic drug acting on AMPA receptors, and was demonstrated to have promising in vivo
properties in the rat and monkey brains. In the current study, we performed a human PET study using [11C]HMS011
to evaluate its safety and kinetics.

DOI 10.1186/s13550-017-0313-0

September 4, 2017

Automated synthesis of 1-[11C]acetoacetate on a TRASIS AiO module

Kiran Kumar Solingapuram Sai, H. Donald Gage, Frankis Almaguel, Bryan Neth, Timothy M. Hughes, Sebastien Tremblay, Christian-Alexandre Castellano, Stephen C. Cunnane, Matthew J. Jorgensen, Suzanne Craft, Akiva Mintz

We automated radiochemical synthesis of 1-[11C]acetoacetate in a commercially available radiochemistry module, TRASIS AllinOne by [11C]carboxylation of the corresponding enolate anion generated in situ from isopropenylacetate and MeLi, and purified by ion-exchange column resins.1-[11C]acetoacetate was synthesized with high radiochemical purity (95%) and specific activity (~ 66.6 GBq/µmol, n = 30) with 35% radiochemical yield, decay corrected to end of synthesis. The total synthesis required ~ 16 min. PET imaging studies were conducted with 1-[11C]acetoacetate in vervet monkeys to validate the radiochemical synthesis. Tissue uptake distribution was similar to that reported in humans ...

August 29, 2017

Production of [18F]F-Py-TFP as a secondary labelling precursor on a cassette based synthesis unit towards a GMP-compliant and convenient fluoroarylation of [18F]-peptides and [18F]-peptidomimetics

O. C. Neels, Y. Remde, M. Schäfer, D. Burkert, K. Kopka, J. Cardinale; German Cancer Research Center, Heidelberg, GERMANY.

Aim: The synthesis and purification of prosthetic groups for the radiofluorination of peptides are sophisticated and therefore difficult to translate into routine production. The aim is to transfer the synthesis of [ 18F]F-Py-TFP (6-[18F]fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester) as reported by Olberg et al. onto a cassette-based radiosynthesizer for large-scale GMP-compliant automated production ready for subsequent labelling of peptides. Materials and Methods: An aqueous solution containing [18F]fluoride was obtained by nuclear reaction (18O(p,n)18F) from a Scanditronix MC32NI cyclotron, transferred to a Trasis AllinOne synthesis module, trapped on and eluted from a QMA cartridge using TBA-HCO3 in water and acetonitrile as the eluent ...

August 29, 2017

[68Ga] peptide high-output production on commercially available MiniAiO® synthesizer

C. COLLET1,2, S. Remy1,2, R. Didier1,2, N. Véran3 , G. Karcher1,2,3; 1 Nancyclotep, Vandoeuvre-les-Nancy, FRANCE, 2 Université de Lorraine, Vandoeuvre-les-Nancy, FRANCE, 3 CHRU Nancy-Brabois, Vandoeuvre-les-Nancy, FRANCE.

Introduction: Gallium-68 is a metallic positron emitter with a half-life of 68 min that is ideal for labelling small peptides as radiopharmaceuticals thanks to the use of a chelating agent with several clinical applications. Numerous gallium-68 labelled peptides (eg. [68Ga]DOTA-TOC/-NOC, [ 68Ga]HBED-PSMA-11, [68Ga]NODAGA-RGD) have shown their interest [1,2]. Developing an easy, rapid and performant labelling method is important. Different methods for the pre-purification of the generator eluate have been explored in the literature, although recent improvement on some generator brands (i.e. low 68Ge breakthrough and low metallic impurities content), makes this pre-purification unnecessary. Development of a labelling process, GMP-compatible and reproducible, using a commercial synthesis module for every peptide labelling is a real challenge for the nuclear medicine. The method presented herein uses a cassette-based approach and a MiniAiO (mAiO, Trasis®) module and has been tested with the IGG100 68Ge/68Ga generators ...

June 1, 2017

First single-use cassette for the automated high-output production of [11C]Choline

C. Lentz, T. Vergote, S. Lacroix, J. Van Naemen, E. Luciani, K. Milloudi, E. Mulleneers, K. Thibaut, S. Goldman, G. Philippart, J.-L. Morelle.

Carbon-11 is metabolically the best nuclide for PET. The dominant use of Fluorine-18 is essentially due to a more convenient half-life time for commercial distribution (110 minutes for 18F vs only 20 minutes for 11C) and a low β energy. Choline, which is an essential nutrient involved among others in cell-membrane signaling after phosphorylation in phosphorylcholine, is compulsing for cellular proliferation, especially for malignant tumors in which cellular growth is high. Nowadays, [11C]Choline is mostly used as a PET radiopharmaceutical for imaging tumors in the brain, esophagus, rectum, prostate and urinary bladder. In contrast to [18F]FDG, the uptake of [11C]Choline is negligible in the brain and urinary tract resulting in highly sensitive imaging of tumors near those benign structures. This compound, however, had never been automated on an easy-to-use disposable system.

May 19, 2017

Fully automated [18F]FAZA production on AllInOne at commercial scale.

M. Otabashi ; C. Vriamont ; T . Vergote ; C. Desfours ; J-L. Morelle and G. Philippart

Tumor hypoxia is a common feature of many solid malignant tumors. Hypoxic cells are known to be more than three times more resistant than those with normal oxygenation levels. It’s believed that hypoxia associated with malignant progression leads to an increase of the tumor invasive potential. The identification and quantification of such type of tumors will thus improve the monitoring and treatment of this kind of tumors. Many radio tracers have been used to diagnosis this type of tumors including [18F]FRP-170, [18F]FETNIM, [18F]FETA, [18F]FMISO and [18F]FAZA (1). The latter two are the most commonly used tracer for tumor hypoxia, although [18F]-FAZA gives much better images with very high contrast due to its quick clearance from blood and non-target tissue (3).
There is thus a strong need for an efficient fully automated method to match the needs of the market to this marker. We present hereby a fully automated method to produce  [18F]-FAZA with high reproducible yield.


May 19, 2017

High reproducible yield [18F]-FCholine production on AllinOne at commercial scale

M. Otabashi ; C. Vriamont ; T. Vergote ; C. Desfours ; J-L. Morelle and G. Philippart

[18F]-Fluorocholine is used with Positron Emission Tomography to detect metastatic prostate cancer [1], recurrent brain tumors and hepatocellular carcinoma [2,3]. Automated methods to synthesize [18F]-Fluorocholine are available on several radiosynthesis platforms, but these approaches suffer from fluctuations of yield, emission of radioactive gas when using the older dibromomethane method and high quantity of 2-Dimethylethanolamine (DMEA) in the final product. Herein, we present an automated one-pot method with an improved purification for the efficient routine production of [18F]-Fluorocholine under cGMP conditions, avoiding the pitfalls of the gaseous method.


May 19, 2017

High yield [18F]FET production on AllinOne (Trasis) at commercial scale

M. Otabashi, C. Vriamont, T. Vergote, C. Desfours, J-L. Morelle and G. Philippart

O-(2-[18F] fluoroethyl)-L-tyrosine ([18F]FET), a 18F-labeled amino acid for imaging amino acid metabolism in tumors, shows high uptake in the primary brain tumors (PBT). [18F]FET overcomes disadvantages of [18F]FDG and [11C] methionine tracers: [18F]FET is more specific than FDG and benefit from the longer half-life versus [11C] tracers. Accordingly, [18F]FET PET is a highly relevant tool for patient management [1-3]. Therefore, a robust synthesis combined with a high yield is requested and has been achieved by Trasis on the AllinOne synthesizer (Figure 1). This process requires no preparation prior to production, operates on ready-to-use consumables and facilitates implementation of GMP.


May 19, 2017

Use of a Trasis AllinOne Synthesizer for routine clinical production of [68Ga]Ga-HBED-11-PSMA and [68Ga]Ga-DOTA-tate and [18F]fluorocholine

D. Stark and T. Vergote

[68Ga]Ga-HBED-11-PSMA (PSMA) and [68Ga]Ga-DOTA-tate (DOTAtate) are two well established PET tracers for diagnostic and staging of prostate cancer (PCa) and neuroendocrine tumours (NET) respectively. In our department we have used a Trasis AllinOne (AiO) synthesiser since late 2014 to routinely produce [68Ga]Ga-DOTA-tate, [18F]fluorocholine ([18F]FCH) and [68Ga]Ga-HBED-11-PSMA. [18F]FCH was initially produced for a comparative clinical trial to demonstrate the superiority of [68Ga]Ga-HBED-11-PSMA compared to [18F]FCH in diagnostic and staging of PCa[1]. In order to produce this range of radiolabelled compounds, a versatile, reliable, cassette based synthesizer was required.

May 5, 2017

Automation of the Radiosynthesis of Six Different 18F-labeled radiotracers on the AllinOne

Shihong Li, Alexander Schmitz, Hsiaoju Lee and Robert H. Mach

Fast implementation of positron emission tomography (PET) into clinical and preclinical studies highly demands automated synthesis for the preparation of PET radiopharmaceuticals in a safe and reproducible manner. The aim of this study was to develop automated synthesis methods for these six 18F-labeled radiopharmaceuticals produced on a routine basis at the University of Pennsylvania using the AllinOne synthesis module.


DOI: 10.1039/c6re00204h