[en] DL-[3-¹¹C]valine, synthesized by phase-transfer alkylation of N-(diphenylmethylene)glycine t-butyl ester with [2-¹¹C]isopropyl iodide, followed by acidic hydrolysis, was obtained in 20-30% radiochemical yield (decay corrected and calculated on the amount of [¹¹C]carbon dioxide used) and with 93-99% radiochemical purity with a total synthesis time of 50 min. Following treatment with immobilized D-amino acid oxidase, L-[3-¹¹C]valine was obtained in 90-99% enantiomeric excess with a total synthesis time of 85 min. [2-¹¹C]Isopropyl iodide was obtained in 40 and 90% radiochemical yield and purity respectively, within 12 min calculated from [¹¹C]carbon dioxide. In a typical experiment starting with 150 mCi of [¹¹C]carbon dioxide, 7 mCi of DL-[3-¹¹C]valine and 0.8 mCi of L-[3-¹¹C]valine were obtained. (author)

[en] The discovery of neuroendocrine differentiation in hormone-refractory prostatic adenocarcinoma has opened a potentially new therapeutic approach in this group of patients with a poor prognosis and few effective therapy modalities. Based on previous findings of increased uptake of ¹¹C-5-hydroxytryptophan (¹¹C-5-HTP) in neuroendocrine tumours using the PET technique, this tracer was applied in the study of 10 patients with metastatic hormone-refractory prostatic adenocarcinoma. In three patients, the study was repeated after treatment. An increased uptake of ¹¹C-5-HTP was observed in all investigated skeletal lesions, although the magnitude of the uptake was moderate. The difference between the standard uptake values (SUV) in normal bone and metastatic lesions was significant (p < 0.001). A kinetic analysis of the uptake of ¹¹C-5-HTP demonstrates an increase during the first minutes followed by a wash-out and a stabilization of the tissue/blood ratio at about 2. The Patlak plots demonstrated a gradual increase in the transport rate during the first 20 to 30 min, after which a constant level was observed. The SUV varied between patients and between lesions over time and treatment. The uptake of ¹¹C-5-HTP discriminates metastatic lesions from normal bone and may thus aid in the diagnosis and, potentially, in treatment monitoring of metastatic hormone-refractory prostatic adenocarcinoma. Uptake kinetics are characterized by a wash-out and cannot alone be used as proof of neuroendocrine differentiation in hormone-refractory prostatic adenocarcinoma

[en] Over recent years, within the community of radiopharmaceutical sciences, there has been an increased incidence of incorrect usage of established scientific terms and conventions, and even the emergence of ‘self-invented’ terms. Here, in order to address these concerns, an international Working Group on ‘Nomenclature in Radiopharmaceutical Chemistry and related areas’ was established in 2015 to achieve clarification of terms and to generate consensus on the utilisation of a standardised nomenclature pertinent to the field. Upon open consultation, the following consensus guidelines were agreed, which aim to: Provide a reference source for nomenclature good practice in the radiopharma-ceutical sciences; Clarify the use of terms and rules concerning exclusively radiopharmaceutical terminology, i.e. nuclear- and radiochemical terms, symbols and expressions; Address gaps and inconsistencies in existing radiochemistry nomenclature rules; Provide source literature for further harmonisation beyond our immediate peer group (publishers, editors, IUPAC, pharmacopoeias, etc.).

[en] The prospects for using carbon-11 labelled compounds in molecular imaging has improved with the development of diverse synthesis methods, including ¹¹C-carbonylations and refined techniques to handle [¹¹C]carbon monoxide at a nanomole scale. Facilitating biological research and molecular imaging was the driving force when [¹¹C]carbon monoxide was used in the first in vivo application with carbon-11 in human (1945) and when [¹¹C]carbon monoxide was used for the first time as a chemical reagent in the synthesis of [¹¹C]phosgene (1978). This review examines a rich plethora of labelled compounds synthesized from [¹¹C]carbon monoxide, their chemistry and use in molecular imaging. While the strong development of the ¹¹C-carbonylation chemistry has expanded the carbon-11 domain considerably, it could be argued that the number of ¹¹C-carbonyl compounds entering biological investigations should be higher. The reason for this may partly be the lack of commercially available synthesis instruments designed for ¹¹C-carbonylations. But as this review shows, novel and greatly simplified methods to handle [¹¹C]carbon monoxide have been developed. The next important challenge is to make full use of these technologies and synthesis methods in PET research. When there is a PET-tracer that meets a more general need, the incentive to implement ¹¹C-carbonylation protocols will increase.

[en] Introduction: The enzyme β-secretase 1 (BACE-1) is associated with the catalytic cleavage of amyloid precursor protein (APP) which leads to the production of amyloid-β, an amyloidogenic peptide that forms insoluble fibrils and is linked to neurodegeneration and Alzheimer's disease (AD). A PET-radioligand for the quantification of BACE-1 would be useful for the understanding of AD. In this report, we describe the synthesis and carbon-11 radiolabeling of a potent hydroxyethylamine BACE-1 enzyme inhibitor (BSI-IV) and its evaluation in vitro and in vivo. Methods: "1"1[C]-N"1-((2S,3R)-4-(cyclopropylamino)-3-hydroxy-1-phenylbutan-2-yl) -5-(N-methylmethyl-sulfonamido)-N"3-((R)-1-phenylethyl)isophthalamide, a β-secretase inhibitor, denoted here as ["1"1C]BSI-IV was synthesized through a palladium-mediated aminocarbonylation with an aryl halide precursor (I or Br) and ["1"1C]CO. The effect of different palladium/ligand-complexes on radiochemical yield in the carbonylative reaction was investigated. The binding of the labeled compound to BACE-1 enzyme was studied in vitro by frozen section autoradiography from brains of healthy rats. Dynamic small animal PET-CT studies and ex vivo biodistribution were performed in male rats. Results: The halide precursors were synthesized in six steps starting from methyl-3-nitrobenzoate with an overall yield of 21–26%. ["1"1C]BSI-IV was obtained in 29 ± 12% decay corrected radiochemical yield (n = 12) with a specific activity of 790 ± 155 GBq/μmol at the end of synthesis with a radiochemical purity of > 99%. The preclinical studies showed that ["1"1C]BSI-IV has a rapid metabolism in rat with excretion to the small intestines. Conclusion: "1"1[C]BSI-IV was obtained in sufficient amount and purity to enable preclinical investigation. The preclinical studies showed low specific binding in vitro and fast clearance in vivo and a low uptake in the brain. These findings suggests that ["1"1C]BSI-IV has limited use as a PET-ligand for the study of BACE-1 or AD

[en] Introduction: 5-Hydroxy-[β-¹¹C]-L-tryptophan ([¹¹C]HTP) is an established positron emission tomography (PET) imaging agent for neuroendocrine tumors (NETs). It has also been used for other clinical research purposes in neurology and diabetes. However, its widespread use is limited by the short physical half-life of the radionuclide and a difficult radiosynthesis. Therefore, a Fluorine-18 labeled analogue, 5-[¹⁸F]Fluoro-L-tryptophan ([¹⁸F]FTRP), has been proposed as a functional analogue. There is no published method for the synthesis of L-[¹⁸F]FTRP. We have therefore developed a synthesis of 5-fluoro-[β-¹¹C]-L-tryptophan ([¹¹C]FTRP), based on the existing chemo-enzymatic method for [¹¹C]HTP and evaluated the potential usefulness of radiolabeled FTRP as a substitute for [¹¹C]HTP. Methods: The in vitro and in vivo behavior of [¹¹C]FTRP, including the dependence of key enzymes in the serotonergic metabolic pathway, was investigated in NET cell lines, NET xenograft carrying immunodeficient mice, normal rats and in non-human primate. [¹¹C]HTP was used for direct comparison. Results: Uptake of [¹¹C]FTRP in NET cell lines in vitro was mediated by enzymes involved in serotonin synthesis and metabolism, similar to [¹¹C]HTP. In vivo biodistribution, either in rodent or non-human primate, was not affected by selectively inhibiting enzymatic steps in the serotonergic metabolic pathway. Conclusion: [¹¹C]FTRP has in vitro biological function similar to that of [¹¹C]HTP. However, this function is not retained in vivo as shown by biodistribution and PET/CT studies. Radiolabeled FTRP is thus not likely to provide an advantage over [¹¹C]HTP in PET imaging in oncology, neurology or diabetes

[en] [${}^{11}$C]Metomidate positron emission tomography (PET) is currently used for staging of adrenocortical carcinoma and for lateralization in primary aldosteronism (PA). Due to the short half-life of carbon-11 and a high non-specific liver uptake of [${}^{11}$C]metomidate there is a need for improved adrenal imaging methods. In a previous pre-clinical study para-chloro-2-[${}^{18}$F]fluoroethyletomidate has been proven to be a specific adrenal tracer. The objective is to perform a first evaluation of para-chloro-2-[${}^{18}$F]fluoroethyletomidate positron emission computed tomography ([${}^{18}$F]CETO-PET/CT) in patients with adrenal tumours and healthy volunteers. Fifteen patients underwent [${}^{18}$F]CETO-PET/CT. Five healthy volunteers were recruited for test-retest analysis and three out of the five underwent additional [${}^{15}$O] water PET/CT to measure adrenal blood flow. Arterial blood sampling and tracer metabolite analysis was performed. The kinetics of [${}^{18}$F]CETO were assessed and simplified quantitative methods were validated by comparison to outcome measures of tracer kinetic analysis. Uptake of [${}^{18}$F]CETO was low in the liver and high in adrenals. Initial metabolization was rapid, followed by a plateau. The kinetics of [${}^{18}$F]CETO in healthy adrenals and all adrenal pathologies, except for adrenocortical carcinoma, were best described by an irreversible single-tissue compartment model. Standardized uptake values (SUV) correlated well with the uptake rate constant K${}_1$. Both K${}_1$ and SUV were highly correlated to adrenal blood flow in healthy controls. Repeatability coefficients of K${}_1$, SUV${}_{65-<!--\; ???\; -->70}$, and SUV${}_{120}$ were 25, 22, and 17%. High adrenal uptake combined with a low unspecific liver uptake suggests that [${}^{18}$F]CETO is a suitable tracer for adrenal imaging. Adrenal SUV, based on a whole-body scan at 1 h p.i., correlated well with the net uptake rate K${}_i$.

No abstract available

[en] Objectives: Fibrosis affecting functionality of vital organs such as liver, lung, heart, and kidney, is involved in many chronic diseases. Positron emission tomography (PET) would not only provide precise localization and extent of the affected tissue but also allow the accurate quantification of the fibrotic process for the subsequent prognosis. Methods: A cyclic peptide c[CPGRVMHGLHLGDDEGPC] conjugated either to 2-(4,7-bis(2-(tert-butoxy)-2-oxoethyl)-1,4,7-triazonan-1-yl)acetic acid (NOTA(tBu)_2) or 4-(4,7-bis(2-(tert-butoxy)-2-oxoethyl)-1,4,7-triazacyclononan-1-yl) -5-(tert-butoxy)-5-oxopentanoic acid (NODAGA(tBu)_3) via polyethylene glycol link (PEG_2) was synthesized and labeled with "6"8Ga. Non-specific organ distribution, blood clearance, and excretion were investigated ex vivo in healthy rats. The binding specificity of the radioligands was assessed in vitro using autoradiography on cryosections of dog fibrotic heart tissue. Results: The yield of NOTA-PEG_2-c[CPGRVMHGLHLGDDEGPC] and NODAGA-PEG_2-c[CPGRVMHGLHLGDDEGPC] was 56% and 41%, respectively. Non-decay-corrected radiochemical yield was 80 ± 5% with radiochemical purity of 95 ± 4%. Pharmacokinetic studies in healthy male Sprague–Dawley rats showed fast blood clearance and renal excretion. Lower uptake in liver, spleen, and kidney was found for [["6"8Ga]Ga-NOTA]"+"1-PEG_2-c[CPGRVMHGLHLGDDEGPC] as compared to [["6"8Ga]Ga-NODAGA]"0-PEG_2-c[CPGRVMHGLHLGDDEGPC]. Histologic evaluation of the left ventricle (LV) myocardium from a dog with severe mitral regurgitation (MR), revealed mild to moderate perivascular and subendocardial, and mild diffuse interstitial fibrosis. The tracer binding to the cryosections of the tissue was specific with the equilibrium Kd of 2.3 ± 0.8 μM and 2.1 ± 0.9 μM, respectively for ["6"8Ga]Ga-NO2A-Col and ["6"8Ga]Ga-NODAGA-Col. Conclusions: Two novel peptide based agents for the imaging of fibrosis by PET were developed. Moderation of the biodistribution could be achieved by variation of the charge on the complex moiety of the agents. The combination of the fast clearance from non-target organs as well as organs of interest such as lung, heart, and liver and binding specificity to the target tissue suggests the potential of the analogs for the imaging of fibrosis

No abstract available