We report a facile and effective method for radioiodine-labeled radiopharmaceuticals via copper (I)-catalyzed click chemistry route. In the novel radioiodination method, 5-iodo ((125/131)I)-1, 2, 3-triazoles were synthesized after a 24-h click reaction in organic solvent with a radiochemical yield of 13%. However, in the aqueous phase, the radiochemical yield of the conjugation radioiodine to RGD via click chemistry was 0. This suggested an exchange between hydrogen ion and iodine ion in aqueous phase so that no enough radioiodine was left to conjugate with RGD. We propose different mechanisms of Cu (I)-catalyzed cycloaddition of organic azides and 1-iodo-alkynes in organic phase and aqueous phase.
Click Chemistry ; Iodine Radioisotopes ; Radiopharmaceuticals ; chemical synthesis ; Triazoles ; chemical synthesis

OBJECTIVETo establish a protocol of automated synthesis of 1-(2-chlorophenyl)-N-[(11)C]methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide ((11)C-PK11195) as the positron-emitter-labeled ligand for peripheral benzodiazepine receptor (PBR) using a commercial synthesizer and explore the quality control methods for the resulting product.

METHODS(11)C-methyl iodide ((11)C-CH(3)I) was synthesized via liquid-phase distillation approach using a (11)C-iodomethane synthesizer. (11)C-PK11195 was prepared by (11)C-methylation of 1-(2-chlorophenyl)-N-(1-methylpropyl)-3-isoquinoline carboxamide (N-demethyl-PK 11195) as the precursor with (11)C-CH(3)I and purified by semi-preparative reversed phase high performance liquid chromatography (HPLC). The radiochemical purity, chemical purity and stability of the product were evaluated by HPLC, and the toxicity was assessed in normal mice. The factors that affected (11)C-PK11195 synthesis were also studied.

RESULTS(11)C-PK11195 was successfully synthesized using the TracerLab FX(F-N) synthesizer. The synthesis time was about 35 min from the end of (11)C-carbon dioxide production by cyclotron to the end of (11)C-PK11195 synthesis (EOS), with a (11)C-methylation reaction time of 3-4 min. The uncorrected radiochemical yield for (11)C-methylation was (33-/+5)%. Analysis with radio-analytical HPLC showed a radiochemical purity and chemical purity of the product both exceeding 99%, with a specific radioactivity of 30-65 GBq/micromol at EOS (from the end of radionuclide production). The (11)C-PK11195 synthesized was radiochemically stable at room temperature and showed low toxicity in normal mice.

CONCLUSIONThe (11)C-PK11195 injection can be conveniently prepared using an automated synthesizer for clinical use in positron emission tomography.

Animals ; Carbon Radioisotopes ; Contrast Media ; chemical synthesis ; Isoquinolines ; adverse effects ; chemical synthesis ; Mice ; Positron-Emission Tomography ; Radioligand Assay ; Radiopharmaceuticals ; adverse effects ; chemical synthesis ; Receptors, GABA-A ; metabolism

Positron emission tomography (PET) is a powerful non-invasive molecular imaging technique for the early detection, characterization, and "real-time" monitoring of disease, and for investigating the efficacy of drugs (Phelps, 2000; Ametamey et al., 2008). The development of molecular probes bearing short-lived positron-emitting radionuclides, such as ¹⁸F (half-life 110 min) or ¹¹C (half-life 20 min), is crucial for PET imaging to collect in vivo metabolic information in a time-efficient manner (Deng et al., 2019). In this regard, one of the main challenges is rapid synthesis of radiolabeled probes by introducing the radionuclides into pharmaceuticals as soon as possible before injection for a PET scan. Although many potential PET probes have been discovered, only a handful can satisfy the demand for a highly efficient synthesis procedure that achieves radiolabeling and delivery for imaging within 1-2 radioisotope half-lives. Only a few probes, such as 2-deoxy-2-[¹⁸F]fluoro-D-glucose (¹⁸F-FDG) and [¹⁸F]fluorodopa, are routinely produced on a commercial scale for daily clinical diagnosis (Grayson et al., 2018; Carollo et al., 2019).
Lab-On-A-Chip Devices ; Positron-Emission Tomography/methods* ; Radioisotopes/chemistry* ; Radiopharmaceuticals/chemical synthesis* ; Solid Phase Extraction

OBJECTIVEThe synthesis, biodistribution, and animal imaging of 99mTc- hydrazinonicotinamide-folate (99mTc-HYNIC-Folate) were studied as a folate receptor-targeted tumor imaging agent.

METHODSHYNIC-Folate was synthesized by a muti-step reaction and radiolabeled with 99mTc using tricine and trisodium phenylphosphine-3, 3', 3"-trisulfonate (TPPTS) as coligands. The radiochemical purity and stability of 99mTc HYNIC-Folate was measured. The biodistributions of 99mTc-HYNIC-Folate in normal mice and tumor-bearing mice were detected. Whole-body gamma imaging was performed using an athymic mouse tumor xenograft model.

RESULTSThe ligand HYNIC-Folate was successfully synthesized and characterized by hydrogen nuclear magnetic resonance (1HNMR) and mass spectrometry (MS). The radiochemical purity of 99mTc-HYNIC-Folate was 96% under optimal conditions. Data from gamma scintigraphy and the biodistribution in tumor-bearing mice showed that 99mTc-HYNIC-Folate predominantly accumulated in tumor, its uptake rate per gram tissue alpham was 5. 620+/- 0. 753. The uptakes of 99mTc-HYNIC-Folate in the other non-target tissues were very low, except it was high in the kidneys ( am was 41. 959 +/-6. 759) .

CONCLUSION99mTc-HYNIC-Folate has the potential to be used as a noninvasive radiodiagnostic imaging agent for the detection of folate receptor-positive human cancers.

Animals ; Female ; Mice ; Mice, Inbred BALB C ; Mice, Inbred ICR ; Neoplasms, Experimental ; diagnostic imaging ; Organotechnetium Compounds ; chemical synthesis ; pharmacokinetics ; Radionuclide Imaging ; Radiopharmaceuticals ; chemical synthesis ; pharmacokinetics ; Tissue Distribution

OBJECTIVE: To study automated synthesis of 2-[(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG) via on-column hydrolysis. METHODS: Automated synthesis of (18)F-FDG was performed by the on-column hydrolysis procedure in TRACERlab FXF-N synthesizer. (18)F-FDG injection was obtained via nucleophilic fluorination of 1, 3, 4, 6-tetra-O-acetyl-2-O-trifluoromethanesulfony-beta-D-mannopyranose as the precursor molecule with (18)F-fluoride, hydrolysis of the (18)F-labeled intermediate on SEP-PAK C18 cartridges with 2 mol/L NaOH solution, and purification and neutralization with SEP-PAK cartridges. RESULTS: The uncorrected radiochemical yield of (18)F-FDG was more than 60% within the total synthesis time shorter than 20 min. The radiochemical purity of (18)F-FDG was above 99%. CONCLUSION On-column hydrolysis is simple and practical for the automated synthesis of (18)F-FDG. (18)F-FDG injection produced by this procedure can be used in clinical PET imaging.
Adult ; Aged ; Automation ; methods ; Fluorodeoxyglucose F18 ; chemical synthesis ; Humans ; Hydrolysis ; Kidney Neoplasms ; diagnostic imaging ; Liver Neoplasms ; diagnostic imaging ; Male ; Positron-Emission Tomography ; Radiography ; Radiopharmaceuticals ; chemical synthesis

AIMTo develop S-(2-18F-fluoroethyl)-L-methionine (18FEMET) as an amino acid positron emission tomography (PET) tracer for tumors, and to evaluate the value of 18FEMET in the differentiation of experimental tumor and experimental inflammation.

METHODS18FEMET was prepared by nucleophilic fluorination reaction via a two-step procedure. Biodistribution of 18FEMET in normal mice, carcinoma-bearing mice and inflammatory mice, and 18FEMET PET imaging for carcinoma-bearing mice and inflammatory mice were performed compared with 2-[18F] fluoro-2-deoxy-D-glucose (FDG) and O-(2-[18F] fluoroethyl)-L-tyrosine (FET).

RESULTSThe overall radiochemical yield with no decay correction was 15%-25%, the whole synthesis time was about 70 min by manual operation, and the radiochemical purity was above 95%. High uptake and long retention of 18FEMET in pancreas, kidney, colon, liver and heart were observed. But low uptakes in brain and blood were found. Furthermore, high uptake of 18FEMET, FDG and FET in tumor, high uptake of FDG in inflammatory tissue, and almost no uptake of 18FEMET and FET in inflammatory tissue were also observed.

CONCLUSION18FEMET is easy to prepare and can be used to differentiate between tumor and inflammatory tissue. It seems to be a potential amino acid tracer for tumors with PET imaging.

Animals ; Fluorodeoxyglucose F18 ; pharmacokinetics ; Inflammation ; diagnostic imaging ; Methionine ; analogs & derivatives ; chemical synthesis ; pharmacokinetics ; Mice ; Neoplasm Transplantation ; Radiopharmaceuticals ; chemical synthesis ; pharmacokinetics ; Sarcoma 180 ; diagnostic imaging ; pathology ; Tissue Distribution ; Tomography, Emission-Computed ; Tumor Cells, Cultured ; Tyrosine ; analogs & derivatives ; chemical synthesis ; pharmacokinetics

The purpose of this study is to prepare 99mTc-HEDTMP [N-(2-hydroxyethyl) ethlenediamine-1,1,2-tri (methylene phosphonic acid), a new kind of bone seeking compound; to investigate its biological properties; and to explore the possibility of using it as a potential radiopharmaceutical for skeleton scintigraphy. HEDTMP was labeled with 99mTc by "pretinning" method, the radiochemical purity was 97.00% +/- 0.34%. 99mTc-HEDTMP was found to be stable in 5 hours in vitro with the radiochemical purity over 95% even after being diluted by physiological saline with the factor of dilution 100. The plane bone scanning of rabbits showed that 99mTc-HEDTMP was principally absorbed by skeletal system. Skull, spine and legs could be observed clearly, and were more legible than the images of 99mTc-MDP. Mice trial also indicated the high bone seeking of 99mTc-HEDTMP. The skeletal uptake was 11.92% ID/g, 13.19% ID/g, 10.14% ID/g, 10.04% ID/g, 7.71% ID/g separately at 30 minutes, 1 hour, 3 hours, 6 hours and 24 hours after the injection. Kidney seemed to be the major excretory organ. The clearance of blood was quick and the retaining amount in non-target organs was small. These results indicate that 99mTc-HEDTMP can be prepared easily, and its biological properties can be compared favorably with the commonly used bone imaging agent, and it is well worth further researching as a promising potential radiopharmaceutical in nuclide diagnosis for skeleton diseases.
Animals ; Bone and Bones ; diagnostic imaging ; metabolism ; Female ; Male ; Mice ; Organotechnetium Compounds ; chemical synthesis ; pharmacokinetics ; Rabbits ; Radiopharmaceuticals ; chemical synthesis ; pharmacokinetics ; Random Allocation ; Technetium Tc 99m Medronate ; pharmacokinetics ; Tissue Distribution ; Tomography, Emission-Computed, Single-Photon

The objective of this research work is to prepare a new and reliable radiopharmaceutical for osteoarthral cartilage imaging. Chondroitin sulfate (CS) was labeled directly with 99mTc by "pretinning" method, the labeling efficiency was 79.30% +/- 1.72% and radiochemical purity was 90.12% +/- 1l.23% after filtration by use of asepsis filter membrane. The biodistribution of 99Tc-CS was studied at 10, 30 min and 1, 2, 3, 4, 5, 6, 7, 8, 9 h respectively after caudal vein injection in normal mice,which showed that the radiolabeled product was washed out from blood quickly, and it was mainly excreted through kidney, but 99mTc-CS had distinctive characteristic of philo- cartilage. Scintigraphy of 99mTc-CS was performed on the rabbit with ostarthritis at 5 h after intravenous injection; the scintigram was clear,and the focus showed increased radiopharmaceutical uptake. The radioactivity ratio of the injured/uninjured side (T/NT) calculated over the region of interest (ROI) was 3.0 +/- 0.6 (P < 0.05). These results indicate that 99mTc-CS is an easily prepared compound with the characteristic of high philo-cartilage and it may be a new ideal cartilage imaging agent.
Animals ; Cartilage, Articular ; diagnostic imaging ; Chondroitin Sulfates ; Female ; Male ; Mice ; Mice, Inbred BALB C ; Organotechnetium Compounds ; chemical synthesis ; Osteoarthritis ; diagnostic imaging ; Rabbits ; Radionuclide Imaging ; Radiopharmaceuticals ; chemical synthesis ; Random Allocation

OBJECTIVETo explore the methods for labeling CDTPA-coupled CD45 monoclonal antibody (mAb) with yttrium-90 ((90)Y) for potential acute myeloid therapy.

METHODSCD45 mAb was labeled with (90)Y by CDTPA and the labeling rate, radiochemical purity, final specific activity, and immunological activity of the mAb were detected.

RESULTSWith the optimal molar ratio of CDTPA/Ab at 20:1, the labeling rate was 95%, radiochemical purity 99.8%, and final specific activity 1.9 mCi/mg. This conjugate was stable in vitro with comparable immunological activity in comparison with unlabeled CD45 mAb.

CONCLUSION(90)Y-CDTPA-CD45 mAb possesses good properties as an ideal targetting therapeutic agent for acute leukemia.

Anhydrides ; chemistry ; Antibodies, Monoclonal ; chemistry ; immunology ; Humans ; Immunoconjugates ; chemistry ; immunology ; Isotope Labeling ; methods ; Leukocyte Common Antigens ; immunology ; Pentetic Acid ; chemistry ; Radiopharmaceuticals ; chemical synthesis ; chemistry ; immunology ; Yttrium Radioisotopes ; chemistry

BACKGROUNDScreening libraries against a molecular target in vitro are idealized models that cannot reflect the real state in vivo where biomolecules coexist and interact. C-terminal amide tripeptides labelled with Technetium-99m can provide a unique noninvasive approach to trace a large number of compounds in vivo.

METHODSThe C-terminal amide tripeptide libraries were synthesized on Rink Amide-MBHA resin using iterative and pooling protocol. Technetium (V) oxo core [TcO(3+)] was bound to each tripeptide via 4 deprotonated nitrogen atoms to form a library of 8000 (99m)Tc tripeptoid complexes. The radiocombinatorial screening (RCS) in vivo was carried out on SD rats and A549 tumour bearing mice.

RESULTSSignals of tissue distribution and metabolism of libraries were recorded by counting or imaging and tissue targeting leads identified by both random and directed RCS. Among them, (99m)Tc RPA, (99m)Tc VIG and (99m)Tc RES had specific tissue targeting in kidney, liver and tumour respectively. The percent injected dose per gram tissue of (99m)Tc labelled leads in their target tissue was highly structure dependent. Because the nontarget tissue binding and the metabolism of (99m)Tc tripeptoid sublibraries were simultaneously monitored successfully by RCS, the interference of background activity was limited to the lowest level. Optimization of renal function agent from the labelled libraries was carried out by directed screening. (99m)Tc DSG was finally identified the most promising agent for renal function studies.

CONCLUSIONSRCS in vivo is a powerful tool for the discovery of tissue targeting drugs. The potential screening bias is probably the major limitation of labelled libraries.

Animals ; Combinatorial Chemistry Techniques ; Drug Design ; Female ; Isotope Labeling ; Kidney Function Tests ; Liver ; diagnostic imaging ; Mice ; Mice, SCID ; Neoplasms, Experimental ; diagnostic imaging ; Peptide Library ; Radionuclide Imaging ; Radiopharmaceuticals ; chemical synthesis ; Rats ; Rats, Sprague-Dawley ; Technetium ; Tissue Distribution