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

Colloidal particle size is an important characteristic that allows mapping sentinel nodes in lymphoscintigraphy. This investigation aimed to introduce different ways of making a 99mTc-tin colloid with a size of tens of nanometers. All agents, tin fluoride, sodium fluoride, poloxamer-188, and polyvinylpyrrolidone (PVP), were mixed and labeled with 99mTc. Either phosphate or sodium bicarbonate buffers were used to adjust the pH levels. When the buffers were added, the size of the colloids increased. However, as the PVP continued to increase, the size of the colloids was controlled to within tens of nanometers. In all samples, phosphate buffer added PVP (30 mg) stabilized tin colloid (99mTc-PPTC-30) and sodium bicarbonate solution added PVP (50 mg) stabilized tin colloid (99mTc-BPTC-50) were chosen for in vitro and in vivo studies. 99mTc-BPTC-50 (<20 nm) was primarily located in bone marrow and was then secreted through the kidneys, and 99mTc-PPTC-30 (>100 nm) mainly accumulated in the liver. When a rabbit was given a toe injection, the node uptake of 99mTc-PPTC-30 decreased over time, while 99mTc-BPTC-50 increased. Therefore, 99mTc-BPTC-50 could be a good candidate radiopharmaceutical for sentinel node detection. The significance of this study is that nano-sized tin colloid can be made very easily and quickly by PVP.
Animals ; Buffers ; Cell Line, Tumor ; Humans ; Lymph Nodes/*radionuclide imaging ; Lymphatic Metastasis ; Metal Nanoparticles/chemistry/ultrastructure ; Mice ; Neoplasms, Experimental/*radionuclide imaging ; Particle Size ; Povidone/*chemistry ; Rabbits ; Radiopharmaceuticals/*chemical synthesis ; Reproducibility of Results ; Sensitivity and Specificity ; Technetium Compounds/*chemistry ; Tin/*chemistry ; Tin Compounds/*chemistry

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

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

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

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

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

This study was undertaken to explore and compare the radiochemical behavior and biological property of antisense oligonucleotide (ASON) labeled with Technetium-99m using two methods: N-hydroxysuccinimidyl S-acetylmercaptoacetyltriglycline (NHS-MAG3) versus hydrazino nicotinamide derivative (SHNH). After SHNH and NHS-MAG3 were synthesized, ASON was labeled with Technetium-99m using SHNH and NHS-MAG3 as a bifunctional chelator, separately. The stability in vivo and in vitro, the combination with plasma albumen of rabbit, the biodistribution in BALB/ C mice and the HT29 cellular uptake were compared between labeled compound 99mTc-SHNH-ASON, using SHNH as a bifunctional complex reagent, and 99mTc-MAG3-ASON, using NHS-MAG3 as a bifunctional chelator. The results revealed that the labeling rate and the stability of 99mTc-MAG3-ASON were evidently higher than that of 99mTc-SHNH-ASON (P < 0.05), the combination rate of 99mTc-MAG3-ASON with plasma albumen was markedly lower than that of 99mTc-SHNH-ASON (P < 0.05); the biodistribution of 99mTc-MAG3-ASON was markedly lower than that of 99mTc-SHNH-ASON in blood, heart, stomach and intestines (P < 0.05), slightly lower than that of 99mTc-SHNH-ASON in liver and spleen (P > 0.05), and markedly higher than that of 99mTc-SHNH-ASON in kidney (P < 0.05); the HT29 cellular uptake rates of 99mTc-MAG3-ASON was markedly higher than that of 99mTc-SHNH-ASON (P < 0.05). Therefore, the radiochemical behavior and biological property of 99mTc-MAG3-ASON labeled using NHS-MAG3 is better than that of 99mTc-SHNH-ASON labeled using SHNH.
Animals ; Colonic Neoplasms ; metabolism ; pathology ; Glycine ; analogs & derivatives ; chemistry ; pharmacokinetics ; Humans ; Isotope Labeling ; methods ; Mice ; Mice, Inbred BALB C ; Niacinamide ; analogs & derivatives ; chemistry ; pharmacokinetics ; Oligonucleotides, Antisense ; chemistry ; pharmacokinetics ; Radiopharmaceuticals ; chemical synthesis ; pharmacokinetics ; Succinimides ; chemistry ; pharmacokinetics ; Technetium Tc 99m Mertiatide ; chemistry ; pharmacokinetics ; Tumor Cells, Cultured

The aim of this study is to explore the optimal labeling condition of technetium-99m labeled antisense oligonucleotides (ASON) DNA and sense oligonueleotides (SON) DNA against multi-drug resistance gene-1 (MIDR1) mRNA, to prepare its two-step icefrozen kits, and to perform the quality control of technetium-99m labeled ASON and SON DNAs and its two-step icefrozen kits. A 20 mer single-stranded ASON sequence and its SON sequence against MDR1 mRNA were synthesized respectively, both of the ASON and SON DNAs were uniform phosphorothioated for this investigation with a primary amine on the 5'-end via a six-carbon alkyl linker, and then were labeled with technetium-99m by conjugating with the bifunctional chelator S-Acetyl NHS-MAG3 to form ASON- and SON-MAC3 DNAs. The optimal labeling condition was explored by varying the amount of ASON- and SON-MAG3 DNAs, SnCl2.2H2O and buffer, the pH value in the reaction medium was also adjusted. The technetium-99m labeled ASON and SON DNAs' two-step icefrozen kits were developed. The radiochemical purities, labeling stability of ASON- and SON-MAG3 DNAs in vivo and vitro were measured, and stability of the two-step icefrozen kits were also studied. The recycled rates of ASON- and SON-MAG3 DNAs were over 70% (n >6), the two-step icefrozen kits of ASON- and SON-MAG3 DNAs were colourless ice crystal. The radiochemical purities of technetium-99m labeled ASON- and SON-MAG3 DNAs were over 92 %. The radiochemical purities were over 90% after stored at room temperature for 24 hours. The kits were stable within 6 months when stored at 0 degrees C, the radiochemical purities of technetium-99m labeled ASON- and SON-MAG3 DNAs were still over 90%. The two-step icefrozen kits of ASON- and SON-MAG3 DNAs were successfully developed. The radiochemical purities were all over 90%. The labeling method was simple, feasible and efficient with good stability.
Animals ; DNA, Antisense ; chemistry ; Isotope Labeling ; methods ; Mice ; Mice, Nude ; Multidrug Resistance-Associated Proteins ; chemistry ; pharmacokinetics ; Oligonucleotides, Antisense ; chemistry ; pharmacokinetics ; Radiopharmaceuticals ; chemical synthesis ; pharmacokinetics ; Random Allocation ; Technetium Tc 99m Mertiatide ; chemistry ; pharmacokinetics

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