Radiochemical Synthesis Research Articles

P-298 - Fully automated radiochemical synthesis of [68Ga]FAPI-4 and its preclinical evaluation for clinical translation

P-298 - Fully automated radiochemical synthesis of [68Ga]FAPI-4 and its preclinical evaluation for clinical translation

Optimization of Automatic Synthesis and Separation of [18F] AV-45 and Quality Control.

Objective: Based on the Tracerlab FXF-N platform, a synthesis program and preparative high-performance liquid chromatography (HPLC) purification program edited by us can stably and repeatedly produce [18F] AV-45 without changing the process. The [18F] AV-45 produced meets the main indexes of radiopharmaceutical intravenous preparations. Methods: The O-toluene sulfonated precursor (1 mg) was subjected to nucleophilic radiofluorination at 115°C in anhydrous dimethyl sulfoxide (DMSO), then the protective group was hydrolyzed by acid. The neutralized reaction mixture was purified through a preparative HPLC then formulated for injection using a C18 purification cartridge. This method yielded a relatively pure [18F] AV-45 product with high specific activity. Results: Four consecutive radiochemical synthesis operations were carried out in this experiment; the average production time of [18F] AV-45 preparation was 60 min, the radiochemical yield was 14.8 ± 2.1% (n = 4), the radiochemical purity was greater than 95%, and the other important quality control indexes met the requirements of radioactive drugs for intravenous administration. Conclusion: This experiment was based on the Tracerlab FXF-N platform with the synthesis program and preparative HPLC purification program edited by us. Through screening and optimization of the separation and purification system and the separation and analysis system, as well as automatic radiochemical synthesis and preparation quality control, intravenous [18F] AV-45 was successfully prepared.

Radiosynthesis and in vivo imaging of [11C]BTFP, a potent inhibitor of VEGFR2

Altered expression of VEGFR2 is reported in the pathology of neurological, neuropsychiatric, brain malignancies and developmental disorders. PET imaging that allows for in vivo visualization of specific targets on the molecular level allows early detection, diagnosis and treatment monitoring non-invasively and accelerates therapeutic development. Our ongoing effort to derive a PET tracer that can be used to quantify the changes in VEGFR2 and resulted in the identification of N-(benzo furan-5-yl)-N-2,6-trimethylfuro[2,3–d]pyrimidin-4-amine (BTFP) (IC50 = 5.8 nM). In this report, the automated radiochemical synthesis and in vivo evaluation of a high affinity VEGFR2 ligand, [11C]BTFP by using PET is described. [11C]BTFP is synthesized in 35 ± 5% radiochemical yield by radiomethylating the N-desmethyl-BTFP precursor using [11C]CH3I. MicroPET studies in mice indicated a blood–brain barrier penetration of [11C]BTFP, with modest uptake and specific binding. Although, the low brain uptake of [11C]BTFP diminished its utility for in vivo imaging application, it can be used as a lead molecule for developing new PET tracers for central nervous system imaging.

Alternative strategies for the synthesis of [11C]ER176 for PET imaging of neuroinflammation

[11C]ER176 is a next generation PET radioligand for imaging 18 kDa translocator protein, a biomarker for neuroinflammation. The goal of this work was to investigate alternative strategies for the radiochemical synthesis, purification, and formulation of [11C]ER176. An optimized tri-solvent high-performance liquid chromatography (HPLC) protocol is described to separate the hydro-de-chlorinated byproduct from [11C]ER176. A newly implemented solid phase extraction work-up efficiently removed HPLC solvent while maintaining chemical purity and overall radiochemical yield and purity. This new HPLC purification and final formulation was completed within 40 min, providing 2.7 ± 0.5 GBq of [11C]ER176 at end of synthesis with 1400 ± 300 GBq/μmol molar activity while meeting all specifications for radiopharmaceutical quality control tests for human research use.

Comparison of amino acid radiotracers L-[methyl-<sup>11</sup> C]methionine and <i>О</i>-2-[<sup>18</sup>F]fluoroethyl-L-tyrosine for PET/CT imaging of cerebral gliomas

Introduction. The radiotracer L-[methyl-11C]methionine (Met) has long been considered the tracer of choice in CNS tumors diagnosis using positron emission tomography, combined with computed tomography (PET/CT). However, there are more and more logistic arguments for the introduction of fluorinated amino acids into diagnostics, in particular, O-2-[18F]fluoroethyl-L-tyrosine (FET), for which our institute has developed its own method of radiochemical synthesis. The aim of the study was to compare amino acid radiotracers L-[methyl-11C]methionine (Met) and O-2-[18F]fluoroethyl-L-tyrosine (FET) in the imaging of cerebral gliomasusing PET/CT. Materials and methods. PET/CT studies using Met and FET were performed in 36 patients (15 men and 21 women) aged 28 to 73 years with suspected intracerebral tumor before surgery of biopsy. Pathohistologicalstudy verified gliomas(n-31) or other tumors (n=3), inflammatory process (n=2). The analysis of results included visual comparison of images, calculation of the tumor-to-brainratio (TBR) and metabolic tumor volume for Met and PET. Results. Visual and quantitative analysis of the scans revealed that tumor uptake pattern of FET was similar to those of Met. No significant differences were found in the TBR of both radiotracers in tumors of different grades of malignancy. A strong significant correlation (r=0,9) was revealed between the TBR of Met and FET in gliomas. There were no significant differences between tumor metabolic volumes when using the same cutoff values for both radiotracers. The ROC analysis established the same diagnostic value of Met and FET in differentiating low and high grade gliomas (area under curve 0,884 and 0,881, respectively). Conclusion. Amino acid radiotracers provide comparable diagnostic information in preoperative imaging of gliomas using PET/CT, which makes it possible to recommend FET as an adequate alternative to Met for PET centers without on-site cyclotron.

Radiochemical Synthesis and Evaluation in Non-Human Primates of 3-[11C]methoxy-4-aminopyridine: A Novel PET Tracer for Imaging Potassium Channels in the CNS.

Demyelination, the loss of the protecting sheath of neurons, contributes to disability in many neurological diseases. In order to fully understand its role in different diseases and to monitor treatments aiming at reversing this process, it would be valuable to have PET radiotracers that can detect and quantify molecular changes involved in demyelination such as the uncovering and upregulation of the axonal potassium channels Kv1.1 and Kv1.2. Carbon-11 labeled radiotracers present the advantage of allowing for multiple scans on the same subject in the same day. Here, we describe [11C]3MeO4AP, a novel 11C-labeled version of the K+ channel tracer [18F]3F4AP, and characterize its imaging properties in two non-human primates including a monkey with a focal brain injury sustained during a surgical procedure 3 years prior to imaging. Our findings show that [11C]3MeO4AP is brain permeable, metabolically stable and has high plasma availability. When compared with [18F]3F4AP, [11C]3MeO4AP shows very high correlation in volumes of distribution (VT), confirming a common target. [11C]3MeO4AP shows slower washout than [18F]3F4AP, suggesting stronger binding. Finally, similar to [18F]3F4AP, [11C]3MeO4AP is highly sensitive to the focal brain injury. All these features make it a promising radioligand for imaging demyelinated lesions.

Automated Radiosynthesis and Molecular Docking Studies of Coumarin- Triazole Hybrid with fluorine-18: A feasibility study.

Fluorine-18 is one of the promising radiotracers that can report target specific information related to its physiology to understand the disease status through the PET modality. In the current study, the radiochemical synthesis, purification, and molecular docking studies of fluorine-18 (18F) radiolabeled coumarin-triazole hybrid have been performed. To develop target specific fluorine-18 radiotracer for the diagnosis in oncology. GE Tracer-lab FX2N module with few modifications in the line connections was used for the radiosynthesis and purification of target molecule [18F]SG-2, 4-((2,6-dimethylmorpholino) methyl)-7-((1-(4-(fluoro-18F) benzyl)-1H-1,2,3-triazol-4-yl) oxy)-2H-chromen-2-one, through the nucleophilic radiofluorination mechanism. The radiochemical purity was measured by HPLC, and TLC analytical methods. The kryptofix levels were also evaluated by using the TLC method. The residual solvents like DMF, ethanol were measured using GC. The Schrödinger drug discovery suite 2018 was used to study the protein and ligand interactions. The quality control parameters revealed the purity, chemical identity, and limits of residual solvents. The radiochemical purity was 95.5 ± 2.3%, and dimethylformamide solvent limit was 89 ± 3 ppm. The molecular docking results had suggested that the cold target molecule has made strong electronic interactions and showed the possible pharmacokinetic (ADME) properties with galectin-1 protein. Overall, these results showed that [[18F]SG-2 radiolabeling with 18F radionuclide was feasible, and support of molecular docking studies suggest possible interactions with Galectin- 1. we reported a feasibility study for labeling coumarin-triazole hybrid with fluorine-18 through aromatic nucleophilic fluorination reaction (SNAr).

Gamma Radiation Synthesis of Silver Nanoparticles/Chitosan composites with antimicrobial properties

Composites of Silver nanoparticles/chitosan were obtained in aqueous solution, in-one step and eco-friendly synthesis, under ambiental conditions, using gamma irradiation. The radiochemical synthesis enabled obtaining of controlled size, monodisperse and high stability Silver nanoparticles. The obtained composites presented UV-Vis surface plasmon resonance comprised between 406-414 nm, depending on composition of the reactant system, spherical shape and narrow particle size distributions, with mean dimensions between 3-55 nm, and good antibacterial properties proven against Staphylococcus aureus and Escherichia coli. The influence of the Silver ions/chitosan ratio and of the pH of the initial solution on the final Ag Np properties is also discussed.

Preclinical Evaluation of 213Bi- and 225Ac-Labeled Low-Molecular-Weight Compounds for Radiopharmaceutical Therapy of Prostate Cancer.

Prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical therapy is a new option for patients with advanced prostate cancer refractory to other treatments. Previously, we synthesized a β-particle-emitting low-molecular-weight compound, 177Lu-L1 which demonstrated reduced off-target effects in a xenograft model of prostate cancer. Here, we leveraged that scaffold to synthesize α-particle-emitting analogs of L1, 213Bi-L1 and 225Ac-L1, to evaluate their safety and cell kill effect in PSMA-positive (+) xenograft models. Methods: The radiochemical synthesis, cell uptake, cell kill, and biodistribution of 213Bi-L1 and 225Ac-L1 were evaluated. The efficacy of 225Ac-L1 was determined in human PSMA+ subcutaneous and micrometastatic models. Subacute toxicity at 8 wk and chronic toxicity at 1 y after administration were evaluated for 225Ac-L1. The absorbed radiation dose of 225Ac-L1 was determined using the biodistribution data and α-camera imaging. Results:213Bi- and 225Ac-L1 demonstrated specific cell uptake and cell kill in PSMA+ cells. The biodistribution of 213Bi-L1 and 225Ac-L1 revealed specific uptake of radioactivity within PSMA+ lesions. Treatment studies of 225Ac-L1 demonstrated activity-dependent, specific inhibition of tumor growth in the PSMA+ flank tumor model. 225Ac-L1 also showed an increased survival benefit in the micrometastatic model compared with 177Lu-L1. Activity-escalated acute and chronic toxicity studies of 225Ac-L1 revealed off-target radiotoxicity, mainly in kidneys and liver. The estimated maximum tolerated activity was about 1 MBq/kg. α-Camera imaging of 225Ac-L1 revealed high renal cortical accumulation at 2 h followed by fast clearance at 24 h. Conclusion:225Ac-L1 demonstrated activity-dependent efficacy with minimal treatment-related organ radiotoxicity. 225Ac-L1 is a promising therapeutic for further clinical evaluation.

High-yield synthesis of a tau PET radioligand and its nonradioactive ligand using an alternative protection and deprotection strategy.

Recently developed tau imaging radiopharmaceuticals show specific uptake in tau protein-rich regions in human brains without off-target binding. These radiopharmaceuticals and their nonradioactive reference ligands are generally obtained in low (radio)chemical yields. In the present study, we investigated high-yield synthesis of 18 F-RO948 ([18 F]1) and its nonradioactive ligand (1). The ligand 1 was synthesized by a Suzuki-Miyaura coupling reaction between 9-(4-methoxybenzyl)-9H-pyrrolo[2,3-b:4,5-c']dipyridin-2-yl trifluoromethanesulfonate (3) and 2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (4), followed by oxidative removal of the para-methoxybenzyl (PMB) group with ceric ammonium nitrate (CAN). This two-step reaction gave 1 in 55.8% yield. The precursor for [18 F]1 was synthesized from 3 and 2-nitro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (6). The resulting PMB-protected precursor 8 was obtained in 74.5% yield. [18 F]1 was synthesized by radiofluorination of 8 (radiochemical conversion (RCC): 95.7 ± 1.7%), followed by deprotection of the PMB group with CAN. This one-pot, two-step radiochemical synthesis followed by HPLC purification gave [18 F]1 in high decay-corrected radiochemical yield (54-60%). The RCC of [18 F]fluoride to [18 F]1 in our two-step synthesis method was similar to that in a one-step radiofluorination reaction of a tert-butoxycarbonyl (BOC)-protected precursor 10 that proceeds with concomitant thermal deprotection of the BOC group. Taken together, the results of this study suggest that this high-yield synthesis method is useful for the synthesis of 18 F-labeled (NH)heteroarene compounds.

Synthesis and Initial In Vivo Evaluations of [11C]WX‐132‐18B, a Microtubule PET Imaging Agent

AbstractMicrotubules play an important role in brain functioning and purported to alter in several neurological disorders including Alzheimer's disease, Parkinson disease, malignancies and brain injuries. Creating a molecular imaging probe that binds to microtubules in brain would significantly benefit the diagnosis and stratification of patients based on therapeutic treatments that target neurotubulin pathology. We have previously reported the first‐ and second‐generation microtubule Positron Emission Tomography (PET) ligands, which exhibited blood brain barrier permeability and accumulation in brain. We are continuing the search for new microtubule agents in order to establish the most selective PET agent with optimal attributes for in vivo quantification of the brain microtubules in diseases. Hence, we identified a high‐affinity microtubule agent namely, WX‐MB‐18B (GI50= 1.9 nM, IC50=0.45‐0.99 nM). In addition to the high affinity to microtubules, WX132‐18B has adequate lipophilicity for facile brain entry and also is amenable for 11 C‐radiolabeling. Herein we report the radiochemical synthesis and initial PET evaluation of [11C]WX‐132‐18B in mice to determine its ability for imaging brain microtubules.

Novel benzimidazole-triazole hybrids as apoptosis inducing agents in lung cancer: Design, synthesis, 18F-radiolabeling & galectin-1 inhibition studies

In this study, we have synthesized a new series of benzimidazole-triazole hybrids as galectin-1 (gal-1) mediated apoptosis-inducing agents, and evaluated for their potential anticancer activity against a panel of human cancer cell lines viz. breast cancer (MCF-7 and MDA-MB-231) lung cancer (A-549 and NCI-H460), and human keratinocyte cancer (HaCaT), using MTT assay. The target compound 7c exhibited an excellent growth inhibition against lung cancer (A-549 and NCI-H460) cells with an IC50 value of 0.63 ± 0.21 µM, and 0.99 ± 0.01 µM respectively. The target compound 7c also showed a significant growth inhibition against breast cancer (MCF-7 and MDA-MB-23) with an IC50 value of 1.3 ± 0.18 µM, and 0.94 ± 0.02 µM respectively. In addition, the radiochemical synthesis has been performed using fluorine-18 radionuclide in the GE Tracer-lab FX2N module to prove the target compound 7c as a PET imaging agent. In the final stage, the 18F-7c target compound was successfully purified with 60% ethanol in water. The radiochemical purity was achieved >95% using HPLC, and the residual solvent DMF limit was around 78 ± 3 ppm confirmed by GC analysis. Further, the apoptosis induction by 7c in lung cancer (A-549) cells was confirmed as a result of the decrease in MMP levels, increased percentage of apoptotic cells, and sub G1 phase arrest by JC-1 staining, DAPI staining, annexin V-FITC/PI, and flow cytometric analysis. In addition, the target compound 7c significantly reduced the gal-1 protein levels in a dose-dependent manner as confirmed by ELISA studies. The protein binding studies like Surface Plasmon Resonance (SPR) and Fluorescence Spectroscopy (FS) studies indicated that the target compound 7c is capable of binding to gal-1 with an equilibrium constant (KD) value of 1.19E-06 M, and binding constant (Ka) of 9.5 × 103 M−1 respectively. The in-silico computational studies also revealed possible interactions and pharmacokinetic properties (ADMET) of compound 7c with the binding domain of gal-1. Therefore, the novel benzimidazole-triazole hybrids as apoptosis-inducing agents in lung cancer would be potential cytotoxic and PET imaging agents via gal-1.

Radiosynthesis and evaluation of [18F]FMTP, a COX-2 PET ligand.

The upregulation of cyclooxygenase-2 (COX-2) is involved in neuroinflammation associated with many neurological diseases as well as cancers of the brain. Outside the brain, inflammation and COX-2 induction contribute to the pathogenesis of pain, arthritis, acute allograft rejection, and in response to infections, tumors, autoimmune disorders, and injuries. Herein, we report the radiochemical synthesis and evaluation of [18F]6-fluoro-2-(4-(methylsulfonyl)phenyl)-N-(thiophen-2-ylmethyl)pyrimidin-4-amine ([18F]FMTP), a high-affinity COX-2 inhibitor, by cell uptake and PET imaging studies. The radiochemical synthesis of [18F]FMTP was optimized using chlorine to fluorine displacement method, by reacting [18F]fluoride/K222/K2CO3 with the precursor molecule. Cellular uptake studies of [18F]FMTP was performed in COX-2 positive BxPC3 and COX-2 negative PANC-1 cell lines with unlabeled FMTP as well as celecoxib to define specific binding agents. Dynamic microPET image acquisitionwas performed in anesthetized nude mice (n = 3), lipopolysaccharide (LPS) induced neuroinflammation mice (n = 4), and phosphate-buffered saline (PBS) administered control mice (n = 4) using a Trifoil microPET/CT for a scan period of 60min. A twofold higher binding of [18F]FMTP was found in COX-2 positive BxPC3 cells compared with COX-2 negative PANC-1 cells. The radioligand did not show specific binding to COX-2 negative PANC-1 cells. MicroPET imaging in wild-type mice indicated blood-brain barrier (BBB) penetration and fast washout of [18F]FMTP in the brain, likely due to the low constitutive COX-2 expression in the normal brain. In contrast, a ~ twofold higher uptake of the radioligand was found in LPS-induced mice brain than PBS treated control mice. Specific binding to COX-2 in BxPC3 cell lines, BBB permeability, and increased brain uptake in neuroinflammation mice qualifies [18F]FMTP as a potential PET tracer for studying inflammation.

Insight into the Development of PET Radiopharmaceuticals for Oncology.

While the development of positron emission tomography (PET) radiopharmaceuticals closely follows that of traditional drug development, there are several key considerations in the chemical and radiochemical synthesis, preclinical assessment, and clinical translation of PET radiotracers. As such, we outline the fundamentals of radiotracer design, with respect to the selection of an appropriate pharmacophore. These concepts will be reinforced by exemplary cases of PET radiotracer development, both with respect to their preclinical and clinical evaluation. We also provide a guideline for the proper selection of a radionuclide and the appropriate labeling strategy to access a tracer with optimal imaging qualities. Finally, we summarize the methodology of their evaluation in in vitro and animal models and the road to clinical translation. This review is intended to be a primer for newcomers to the field and give insight into the workflow of developing radiopharmaceuticals.

Automated radiosynthesis and preclinical evaluation of Al[18F]F-NOTA-P-GnRH for PET imaging of GnRH receptor-positive tumors

IntroductionGonadotropin releasing hormone (GnRH) receptor is overexpressed in many human tumors. Previously we developed a 18F-labelled GnRH peptide. Although the GnRH-targeted PET probe can be clearly visualized by microPET imaging in a PC-3 xenograft model, clinical applications of the probe have been limited by complex labeling procedures, poor radiochemical yield, and unwanted accumulation in GnRH receptor negative tissues. In this study, we have designed a new 18F-labelled GnRH peptide that is more amenable to clinical development. MethodsGnRH peptide analogues NOTA-P-GnRH was synthesized and automated radiolabeled with 18F using a Al[18F]F complex on a modified PET-MF-2V-IT-I synthesis module. The GnRH receptor affinities of AlF-NOTA-P-GnRH and NOTA-P-GnRH were determined by in vitro competitive binding assay. For in vitro characterization determination of stability and partition coefficients were carried out, respectively. Dynamic microPET and biodistribution studies of Al[18F]F-NOTA-P-GnRH were evaluated in xenograft tumor mouse models. ResultsThe total radiochemical synthesis and purification of Al[18F]F-NOTA-P-GnRH was completed within 35 min with a decay-corrected yield of 35 ± 10%. The logP value of Al[18F]F-NOTA-P-GnRH was −2.74 ± 0.04 and the tracer was stable in phosphate-buffered saline, and bovine and human serum. The IC50 values of AlF-NOTA-P-GnRH and NOTA-P-GnRH were 116 nM and 56.2 nM, respectively. Dynamic PET imaging together with ex vivo biodistribution analyses revealed that Al[18F]F-NOTA-P-GnRH was clearly delineated in both PC-3 and MDA-MB-231 xenografted tumors. ConclusionAl[18F]F-NOTA-P-GnRH can be efficiently produced on a commercially available automated synthesis module and has potential for use in clinical diagnosis of GnRH receptor-positive tumors. Advances in knowledgeOur studies developed the automated radiosynthesis of a new 18F-labelled GnRH tracer and preclinical evaluation for future clinical application. Implications for patient careQuantitative and noninvasive imaging of GnRH expression would provide information for diagnosis and treatment of cancer patients.

Radiosynthesis of [18F]-Labelled Pro-Nucleotides (ProTides).

Phosphoramidate pro-nucleotides (ProTides) have revolutionized the field of anti-viral and anti-cancer nucleoside therapy, overcoming the major limitations of nucleoside therapies and achieving clinical and commercial success. Despite the translation of ProTide technology into the clinic, there remain unresolved in vivo pharmacokinetic and pharmacodynamic questions. Positron Emission Tomography (PET) imaging using [18F]-labelled model ProTides could directly address key mechanistic questions and predict response to ProTide therapy. Here we report the first radiochemical synthesis of [18F]ProTides as novel probes for PET imaging. As a proof of concept, two chemically distinct radiolabelled ProTides have been synthesized as models of 3′- and 2′-fluorinated ProTides following different radiosynthetic approaches. The 3′-[18F]FLT ProTide was obtained via a late stage [18F]fluorination in radiochemical yields (RCY) of 15–30% (n = 5, decay-corrected from end of bombardment (EoB)), with high radiochemical purities (97%) and molar activities of 56 GBq/μmol (total synthesis time of 130 min.). The 2′-[18F]FIAU ProTide was obtained via an early stage [18F]fluorination approach with an RCY of 1–5% (n = 7, decay-corrected from EoB), with high radiochemical purities (98%) and molar activities of 53 GBq/μmol (total synthesis time of 240 min).

18F-Labeled Small-Molecule and Low-Molecular-Weight PET Tracers for the Noninvasive Detection of Cancer.

Noninvasive molecular imaging of cancer by means of the scintigraphic imaging modalities PET, PET/CT, and PET/MRI represents a powerful diagnostic tool in modern nuclear medicine. Radiotracers labeled with the prominent positron emitter fluorine-18 are routinely used to target and visualize discrete biological structures dysregulated in the progression of cancer. Such tracers are therefore capable of detecting oncological pathologies in vivo at the cellular and subcellular level in a timely manner and are thereby used for early detection of cancer as well as monitoring for treatment response. This chapter describes a variety of important 18F-labeled radiopharmaceuticals that are frequently used in oncological PET imaging. Small-molecule and low-molecular-weight radiotracers for the detection of glucose utilization, amino acid transport, protein synthesis, membrane lipid synthesis, cell proliferation, cell death, hypoxia, estrogen receptor status, prostate-specific membrane antigen (PSMA) expression, and bone mineralization of tumors are introduced. The structural properties, common radiochemical synthesis approaches as well as in vivo metabolism and accumulation mechanisms of the clinically most important 18F-labeled radiotracers are described.

Radiosynthesis and validation of [5-cyano-N-(4-(4-[11 C]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl) furan-2-carboxamide] ([11 C]CPPC), a PET radiotracer for imaging CSF1R, a microglia-specific marker.

In this practitioner protocol, the radiochemical synthesis of [11 C]CPPC is described in detail, and a quality control summary of three validation productions is presented. The results indicate that the radiotracer product can be produced in good radiochemical yield (> 60 mCi (2.22 GBq) at end-of-synthesis (EOS)), at high specific activity (molar activity > 11,435 mCi/μmole (423 GBq/μmole) at EOS) and high chemical and radiochemical purity. The entire production conforms to current Good Manufacturing Practice (cGMP) requirements. The final product is formulated as a sterile, pyrogen-free solution suitable for human injection.

Positron Emission Tomography: Updates on Imaging of Addiction.

Positron Emission Tomography: Updates on Imaging of Addiction.

Gamma Radiation Synthesis of Colloidal Silver Nanoparticles

Radiochemical synthesis of metallic nanoparticles is an eco-friendly method allowing the obtaining of controlled size, well dispersed and highly stable particles at very mild conditions. Colloidal silver nanoparticles were synthesized in a one-step process, in an aqueous system consisting of polyvinyl alcohol (PVA)/Ag+/isopropyl alcohol (IPA), irradiated at various doses by using high energy ionizing radiations (g-rays). The UV-Vis spectra have shown a maximum absorption peak in the range of 390-450 nm, specific for silver nanoparticles. The size of the obtained spherical shape nanoparticles was below 50 nm and decreased with increasing of the irradiation dose.