Automated radiosynthesis of [11 C]UCB-J for imaging synaptic density by positron emission tomography.

An automated radiosynthesis of carbon-11 positron emission tomography radiotracer [11 C]UCB-J for imaging the synaptic density biomarker synaptic vesicle glycoprotein SV2A was established using Synthra RNPlus synthesizer. Commercially available trifluoroborate UCB-J analogue was used as a radiolabelling precursor, and the desired radiolabelled product was isolated in 11 ± 2% (n = 7) nondecay corrected radiochemical yield and formulated as a 10% EtOH solution in saline with molar activities of 20 to 100 GBq/µmol. The method was based upon the palladium(0)-mediated Suzuki cross-coupling reaction and [11 C]CH3 I as a radiolabelling synthon. The isolated product was cGMP compliant as demonstrated by the results of quality control analysis.

A simple and efficient automated cGMP-compliant radiosynthesis of [11 C]metomidate using solid phase extraction cartridge purification.

[11 C]metomidate ([11 C]MTO) is a radiotracer widely used to detect disorders of adrenocortical origin by positron emission tomography (PET) imaging. [11 C]MTO PET/computed tomography (PET/CT) is considered a sensitive and specific noninvasive alternative to adrenal vein sampling (AVS) in the management of primary hyperaldosteronism (PHA). Herein, we report a reliable automated procedure for the routine manufacturing of [11 C]MTO in current good manufacturing practice (cGMP) conditions on the commercial Synthra MeIPlus Loop Vessel synthesizer. The method is based on a combination of the captive-solvent 11 C-methylation of the carboxylate salt 1b of the MTO precursor 1a followed by solid phase extraction (SPE) cartridge purification methodology, which substitutes HPLC purification of the crude reaction mixture. Starting from 45 GBq [11 C]CO2 at the end of bombardment (EOB), 3 GBq of pure [11 C]MTO was produced in 18 minutes with 12% decay corrected radiochemical yield (RCY) at the end of synthesis (EOS) and with the modest molar activity of 13 GBq/µmol at the time of application. Each dose produced met all established quality control (QC) criteria. The method can easily be implemented into other commercial automated radiosynthesizers for manufacturing carbon-11 labeled radiotracers.

18FDG, [18F]FLT, [18F]FAZA, and 11C-methionine are suitable tracers for the diagnosis and in vivo follow-up of the efficacy of chemotherapy by miniPET in both multidrug resistant and sensitive human gynecologic tumor xenografts.

Expression of multidrug pumps including P-glycoprotein (MDR1, ABCB1) in the plasma membrane of tumor cells often results in decreased intracellular accumulation of anticancer drugs causing serious impediment to successful chemotherapy. It has been shown earlier that combined treatment with UIC2 anti-Pgp monoclonal antibody (mAb) and cyclosporine A (CSA) is an effective way of blocking Pgp function. In the present work we investigated the suitability of four PET tumor diagnostic radiotracers including 2-[(18)F]fluoro-2-deoxy-D-glucose ((18)FDG), (11)C-methionine, 3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT), and [(18)F]fluoroazomycin-arabinofuranoside ((18)FAZA) for in vivo follow-up of the efficacy of chemotherapy in both Pgp positive (Pgp(+)) and negative (Pgp(-)) human tumor xenograft pairs raised in CB-17 SCID mice. Pgp(+) and Pgp(-) A2780AD/A2780 human ovarian carcinoma and KB-V1/KB-3-1 human epidermoid adenocarcinoma tumor xenografts were used to study the effect of the treatment with an anticancer drug doxorubicin combined with UIC2 and CSA. The combined treatment resulted in a significant decrease of both the tumor size and the accumulation of the tumor diagnostic tracers in the Pgp(+) tumors. Our results demonstrate that (18)FDG, (18)F-FLT, (18)FAZA, and (11)C-methionine are suitable PET tracers for the diagnosis and in vivo follow-up of the efficacy of tumor chemotherapy in both Pgp(+) and Pgp(-) human tumor xenografts by miniPET.

Daunorubicin and doxorubicin inhibit the [(11)C]choline accumulation in cancer cells.

We studied how very short (10-40min) incubation with anthracycline derivatives modifies the accumulation of PET tumor-diagnostic radiotracers in cancer cells. The human ovarian A2780 and A2780AD, human B lymphoid JY, human epidermoid KB-3-1 and KB-V-1, and smooth muscle DDT1 MF-2 cells were pre-incubated with daunorubicin and doxorubicin, and the uptake of [(18)F]FDG and [(11)C]choline was measured. Anthracycline treatment decreased remarkably the [(11)C]choline accumulation in a concentration dependent manner, while it did not modify significantly the [(18)F]FDG uptake of the cells.

[Synthesis of radiopharmaceuticals for PET investigations]. / Radiogyógyszerek elóállítása pozitronemissziós tomográfiás vizsgálatokhoz.

The PET radiopharmaceuticals are prepared on the spot in most cases due to the short lifetime of the isotopes used. The first step of this process is the isotope production by small cyclotrons. The synthons made from the isotopes react with the precursor of the given radiopharmaceutical. The target compound selected from the reaction mixture is ready for injection after purification, formulation and sterile filtration. In addition to [18F]-FDG, [11C]-methionine and [15O]-butanol routinely used for diagnostic purposes in the PET Centre of the University of Debrecen, a number of other radiopharmaceuticals are synthesized for use in research from time to time.

[Diagnostic possibilities of positron emission tomography in oncologic pulmonology]. / A pozitronemissziós tomográfia alkalmazási lehetóségei a tüdógyógyászati onkológiában.

The authors present the possibilities of applying positron emission tomography (PET) in oncopulmonology. In addition to reviewing the literature, they share their own experience obtained during the diagnostic work-up and follow-up of twenty-three patients. The basic indications and the relevant properties of the most frequently used radiopharmaceuticals are discussed. Finally, the authors raise the question of cost-effectiveness of PET-investigations vs. conventional techniques, and suggest possible algorithms to include this non-invasive imaging method in the diagnostic work-up of patients with malignant or benign pulmonary diseases.

[FDG PET scan of metastases in recurrent medullary carcinoma of the thyroid gland]. / Recidív medullaris pajzsmirigydaganat metastasisainak FDG-PET-vizsgálata.

Searching for metastases of medullary thyroid cancer (MTC), FDG PET was applied. PET results were compared with those of conventional diagnostic imaging procedures. After primary treatment, 52 MTC patients with elevated serum tumor marker levels and/or general symptoms (diarrhoea/flush) underwent radiological (CT/MRI), 131-iodine labeled metaiodo-benzylguanidine (MIBG) whole-body scintigraphy and FDG PET investigations. At least one pathological lesion was detected in 49 patients by PET, 35 by CT, 32 by MRI and 3 by MIBG. FDG PET was far superior to the other methods in identifying metastases in the supradiaphragmatic lymphatic regions. In the follow-up of MTC patients, FDG PET was more sensitive in localizing tumorous LN involvement, especially in the cervical, supraclavicular and mediastinal lymphatic regions, compared to other imaging modalities.

[The [18F]-FNECA serves as a suitable radioligand for PET investigation of purinergic receptor expression]. / A [18F]-FNECA széleskörúen alkalmazható radioligand a purinerg receptorexpresszió PET-vizsgálatához.

The well known and widely used P1 adenosine agonist, 5'-N-ethyl-carboxamidoadenosine (NECA), was labelled with 18F isotope for the in vivo PET investigation of A1, A2 and A3 adenosine receptor expression. The precursor 2-[18F]fluoroethylamine was reacted with 2',3'-O-isopropylideneadenosine-5'-uronic acid. Specific activity of the [18F]-FNECA was (2.3 +/- 1.1) TBq/mmol (60 Ci/mmol). Dynamic PET measurements were carried out in rabbits to study the in vivo kinetics of the receptor saturation with the labelled ligand. The time dependent accumulation was followed up in the heart, lungs, liver, brain and testis. The radiotracer uptake was rapid and reached its maximum in less than two minutes in the heart and testes after v. injection of the radiopharmaceutical, while it took about 6 minutes in the brain, lungs and liver. High [18F]-FNECA accumulation was detected in the intestines, too. The specific binding of the [18F]-FNECA was tested in competition experiments in brain and heart sections using autoradiographic technique. The outlined synthesis provided sufficient amounts of [18F]-FNECA to map adenosine receptor expression under physiological conditions.