D. Stimson

Management of radioactive waste gases from PET radiopharmaceutical synthesis using cost effective capture systems integrated with a cyclotron safety system

The emphasis on the reduction of gaseous radioactive effluent associated with PET radiochemistry laboratories has increased. Various radioactive gas capture strategies have been employed historically including expensive automated compression systems. We have implemented a new cost-effective strategy employing gas capture bags with electronic feedback that are integrated with the cyclotron safety system. Our strategy is suitable for multiple automated 18F radiosynthesis modules and individual automated 11C radiosynthesis modules. We describe novel gas capture systems that minimize the risk of human error and are routinely used in our facility.

Synthesis, characterization and 11C-radiolabeling of aminophenyl benzothiazoles: structural effects on the alkylation of amino group

Several aminophenyl benzothiazoles were prepared with a view to using them as amyloid binding agents for imaging β-amyloid in Alzheimers disease. These precursors were radiolabeled with (11) C-positron-emitting radioisotope using an automated synthesizer and selected radiolabeled compounds were further purified by HPLC. Our results demonstrate that changes in structure have a major influence on the radioactive yield and the ease with which the radiolabel can be introduced. Aminophenyl benzothiazoles with an attached isopropyl group resisted dialkylation perhaps due to steric hindrance caused by this group. Straight chain attachment of methyl, ethyl, butyl, and crotyl groups in the structure decreased the radiochemical yield. Notably, the o-aminophenyl benzothiazole derivatives were difficult to alkylate despite stringent experimental conditions. This reactivity difference is attributed to the hydrogen bonding characteristics of the o-amino group with the nitrogen atom of the thiazole ring.

N -(4-[ 18 F]fluorobenzyl)cholylglycine, a novel tracer for PET of enterohepatic circulation of bile acids: Radiosynthesis and proof-of-concept studies in rats

INTRODUCTION Enterohepatic circulation (EHC) of conjugated bile acids is an important physiological process crucial for regulation of intracellular concentrations of bile acids and their function as detergents and signal carriers. Only few bile acid-derived imaging agents have been synthesized and hitherto none have been evaluated for studies of EHC. We hypothesized that N-(4-[18F]fluorobenzyl)cholylglycine ([18F]FBCGly), a novel fluorine-18 labeled derivative of endogenous cholylglycine, would be a suitable tracer for PET of the EHC of conjugated bile acids, and we report here a radiosynthesis of [18F]FBCGly and a proof-of-concept study by PET/MR in rats. METHODS A radiosynthesis of [18F]FBCGly was developed based on reductive alkylation of glycine with 4-[18F]fluorobenzaldehyde followed by coupling to cholic acid. [18F]FBCGly was investigated in vivo by dynamic PET/MR in anesthetized rats; untreated or treated with cholyltaurine or rifampicin. Possible in vivo metabolites of [18F]FBCGly were investigated by analysis of blood and bile samples, and the stability of [18F]FBCGly towards enzymatic de-conjugation by Cholylglycine Hydrolase was tested in vitro. RESULTS [18F]FBCGly was produced with a radiochemical purity of 96% ± 1% and a non-decay corrected radiochemical yield of 1.0% ± 0.3% (mean ± SD; n = 12). PET/MR studies showed that i.v.-administrated [18F]FBCGly underwent EHC within 40-60 min with a rapid transhepatic transport from blood to bile. In untreated rats, the radioactivity concentration of [18F]FBCGly was approximately 15 times higher in bile than in liver tissue. Cholyltaurine and rifampicin inhibited the biliary secretion of [18F]FBCGly. No fluorine-18 metabolites of [18F]FBCGly were observed. CONCLUSION We have developed a radiosynthesis of a novel fluorine-18 labeled bile acid derivative, [18F]FBCGly, and shown by PET/MR that [18F]FBCGly undergoes continuous EHC in rats without metabolizing. This novel tracer may prove useful in PET studies on the effect of drugs or diseases on the EHC of conjugated bile acids.

A Novel Strategy to Introduce 18F, a Positron Emitting Radionuclide, into a Gallium Nitrate Complex: Synthesis, NMR, X-Ray Crystal Structure, and Preliminary Studies on Radiolabelling with 18F

A hexan-3,4-dione bis(4N-phenylthiosemicarbazone) gallium nitrate complex was synthesised and the structure was confirmed by NMR studies. The complex was prepared using an appropriately substituted dithiosemicarbazone and sodium methoxide in anhydrous methanol. The structure was further confirmed using single crystal X-ray crystallography. The crystal structure of gallium nitrate complex of diphenylthiosemicarbazone comprise a planar configuration of the tetradentate coordinated thiosemicarbazone with the Ga3+ ion, with the nitrate ligand occupying the apical coordination site. The X-ray structure of the gallium fluoride complex of pentan-2,3-dione bis(4N-phenylthiosemicarbazone) has been determined and confirms exchange of the nitrate can be achieved with fluoride. We show facile exchange of 18F, a positron emitter, to form the 18F-gallium complex under mild conditions, thus providing confirmation that such a transformation can be used to introduce 18F directly into nitrate-coordinated complexes of gallium-thiosemicarbozone complexes, a new labelling strategy for the preparation of imaging agents.

Heteronuclear NMR spectroscopic investigations of gallium complexes of substituted thiosemicarbazones including x-ray crystal structure, a new halogen exchange strategy, and 18F radiolabelling

Five thiosemicarbazone ligands have been synthesized, and their coordination chemistry with gallium was investigated. The reaction of these thiosemicarbazones with gallium chloride in alcohol solutions in the presence of a base yielded the corresponding penta-coordinated Ga-Cl metal complexes. In contrast, the reaction of gallium nitrate with the ligands in the presence of alkoxides resulted in the formation of the corresponding Ga-alkoxides, rather than the anticipated Ga-nitrate complex. The crystal structures of gallium chloride and gallium methoxide complexes of diphenylthiosemicarbazone comprise a planar configuration of the tetradentate-coordinated thiosemicarbazone with Ga3+ ion, with the chloride or methoxide groups occupying the apical coordination site. The corresponding ethoxido complex was also prepared in an identical fashion, and NMR analysis confirmed structural similarity to the methoxido complex. Facile halogen exchange reactions of the gallium chloride complexes were achieved by treatment with silver nitrate, followed by addition of KF or KI to generate the gallium fluoride and iodide complexes, respectively. This method of exchange using halogenated inorganic salts aids the preparation of group 13 fluorides, which are notoriously insoluble in organic solvents, for complexation with organic ligands. All compounds have been fully characterized by NMR, and the X-ray crystal structures of two of the complexes are reported. Additionally, the positron-emitting isotope 18F was introduced in the structure of the diphenyl gallium thiosemicarbazone complex.

A FULLY INTEGRATED, COST-EFFECTIVE AND SOPHISTICATED CAPTURE SYSTEM FOR RADIOACTIVE GASES GENERATED DURING AUTOMATED RADIOPHARMACEUTICAL SYNTHESIS

53 year old man with human immunodeficiency virus (HIV) developed 3–4 weeks of severe crampy abdominal pain and nausea. The patient had been started on anti-retroviral therapy only 6 months prior. Computed tomography (CT) scan of the abdomen and pelvis demonstrated lymphadenopathy which was considered suspicious for lymphoma. Fluorodeoxy-glucose Positron Emission Tomography (FDG PET/CT) was performed which demonstrated FDG avid disease above and below the diaphragms. The low dose CT also demonstrated the presence of ‘fat in bowel sign’ with an associated nearby FDG avid mass suggesting a small bowel intussusception. Subsequent Diagnostic CT was co-registered better demonstrating the intussusception without vascular compromise. The patient subsequently underwent a laparotomy. At laparotomy the intussusception was identified and manually reduced. The involved segment of small bowel was resected and sent for surgical pathology. The macroscopic pathological specimen demonstrated an endoluminal mass measuring up to 3.5 cm with a yellow/ fleshy dimpled surface. Histologically the lesion was Classical Mixed Cellularity Hodgkin lymphoma. On immmuno-histochemistry the tumour showed diffuse/strong nuclear positive Ebstein Barr Virus-encoded RNA staining. This is the first case we have identified in the literature of a FDGPET-CT diagnosed small bowel intussusception due to lead point of a Classical Hodgkins lymphoma tumour mass in an adult. P56 A V/Q SCAN LEADING TO THE DIAGNOSIS OF A BRONCHIAL NEUROENDOCRINE (ATYPICAL CARCINOID) TUMOUR R Garzan1, A Aminazad1, M Jost1, F Thien1 1Eastern Health, Melbourne, Australia Background: Apart from the diagnosis of Pulmonary Embolism, V/Q scans can be helpful in establishing alternative diagnoses. Aims: We describe a 59-year-old man whose abnormal V/Q scan led to the final diagnosis of a bronchial Neuroendocrine tumour. Methods: A 59-year old man (life-long non-smoker) presented to the emergency department with several weeks of dyspnea and chest infection Poster Presentations