Tumor PET imaging with radiopharmaceuticals plays a major role in the understanding of tumor biological information and for diagnosis of tumorswith non-invasive methods. These radiopharmaceuticals can be divided into two categories radiopharmaceuticals for metabolic process imaging and for specific receptor imaging. Most tumor imaging radiopharmaceuticals such as [18F]FDG, [18F]FLT, and [11C]choline can be trapped in tumor cells by specific metabolic processes of each radiopharmaceutical and show an increase in metabolism of tumor regions. Unlike these compounds, the hypoxia imaging adiopharmaceuticals such as [18F]FMISO and [64Cu]ATSM are trapped by oxidative metabolic mechanisms under only hypoxic conditions of tumor cells. For tumor specific receptor imaging, [18F]FES for estrogen receptor positive breast cancer may be used and recent clinical results showed the possibility of evaluating tumor therapy responseby estrogen receptor imaging with [18F]FES. This paper gives an overview of the current status of tumor PET imaging adiopharmaceuticals and the development of new lead compounds as potential radiopharmaceuticals by medicinal chemistry.
Anoxia ; Breast Neoplasms ; Chemistry, Pharmaceutical ; Diagnosis ; Estrogens ; Metabolism ; Radiopharmaceuticals*

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 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

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

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

Neurotransmitter imaging with radiopharmaceuticals plays major role for understanding of neurological and psychiatric disorders such as Parkinson's disease and depression. Radiopharmaceuticals for neurotransmitter imaging can be divided to dopamine transporter imaging radiopharmaceuticals and serotonin trnasporter imaging radiopharmaceuticals. Many kinds of new dopamine transporter imaging radiopharmcaeuticals has a tropane ring and they showed different biological properties according to the substituted functional group on tropane ring. After the first clinical trials with [123I]beta-CIT, alkyl chain substituent introduced to tropane ring amine to decrease time for imaging acquisition and to increase selectivity. From these results, [123I]PE2I, [18F]FE-CNT, [123I]FP-CIT and [18F]FP-CIT were developed and they showed high uptake on the dopamine transporter rich regions and fast peak uptake equilibrium time within 4 hours after injection. [11C]McN 5652 was developed for serotonin trnasporter imaging but this compound showed slow kinetics and high background radioactivity. To overcome these problems, new diarylsulfide backbone derivatives such as ADAM, ODAM, AFM, and DASB were developed. In these candidates, [11C]AFM and [11C]DASB showed high binding affinity to serotonin transporter and fast in vivo kinetics. This paper gives an overview of current status on dopamine and serotonin transporter imaging radiopharmaceuitcals and the development of new lead compounds as potential radiopharmaceuticals by medicinal chemistry.
Chemistry, Pharmaceutical ; Depression ; Dopamine ; Dopamine Plasma Membrane Transport Proteins ; Kinetics ; Neurotransmitter Agents* ; Parkinson Disease ; Radioactivity ; Radiopharmaceuticals* ; Serotonin ; Serotonin Plasma Membrane Transport Proteins ; Tomography, Emission-Computed, Single-Photon

OBJECTIVETo establish a labeling method for a specific lung cancer-targeting small molecule peptide cNGQGEQc with ¹³¹I and observe the radioactivity distribution of the labeled peptide in rabbits using single-photon emission computed tomography (SPECT).

METHODSChloramine-T method was used for ¹³¹I labeling of the tyrosine amino group on cNGQGEQc, and the labeling efficiency and radiochemical purity of ¹³¹I-cNGQGEQc were determined with paper chromatography. The stability of ¹³¹I-cNGQGEQc in saline and human serum was assessed after incubation in water bath at 37 degrees celsius; for 24 h. The octanol-water partition coefficient lg P (the radioactivity counting ratio of ¹³¹I-cNGQGEQc dissolved in 100 µl octanol or in 100 µl saline) was calculated. SPECT was performed in 3 male New Zealand white rabbits after intravenous injection of ¹³¹I-cNGQGEQc to observe the dynamic distribution of the peptide with the time-radioactivity curve (T-A curve) of the region of interest (ROI).

RESULTSWith a labeling efficiency of 90%, ¹³¹I-cNGQGEQc showed a radiochemical purity of was 95% after purification with HPLC. The radiochemical purity of ¹³¹I-cNGQGEQc was (93.12 ± 1.18)% and (88.34 ± 5.43)% after intubation in saline and human serum for 24 h, respectively. The octanol-water partition coefficient lg P of ¹³¹I-cNGQGEQc was -1.75, suggesting its hydrosolubility. In rabbits with intravenous injection of ¹³¹I-cNGQGEQc, SPECT visualized the kidneys at 1 min after the injection; the imaging of the heart and liver became attenuated at 5 min when the bladder was visualized with an increasing radioactivity. The radioactivity of the soft tissues began to fade at 30 min. No gallbladder visualization was detected, and the radioactivity of the abdomen remained low. No obvious radioactivity concentration was observed in the thyroid and stomach. The T-A curves of the ROI of all the tissues and organs descended over time.

CONCLUSIONRadiolabeling of cNGQGEQc with ¹³¹I is simple and highly efficient. ¹³¹I-cNGQGEQc has good stability in vitro and good distribution characteristics for in vivo imaging, and is cleared mainly by renal excretion due to its hydrosolubility. These results provide experimental basis for further studies of diagnosis and therapy of lung cancer with targeting polypeptide.

Animals ; Antineoplastic Agents ; pharmacokinetics ; Chloramines ; Humans ; Iodine Radioisotopes ; chemistry ; Lung Neoplasms ; Male ; Peptides ; pharmacokinetics ; Rabbits ; Radiopharmaceuticals ; pharmacokinetics ; Tissue Distribution ; Tomography, Emission-Computed, Single-Photon ; Tosyl Compounds

BACKGROUND/AIMS: The usefulness of 18F-fluoro-2-deoxyglucose (FDG)-PET in detecting primary cancer, lymph node metastasis, and distant metastasis were studied in the gastric cancer patients. METHODS: The subjects were 392 gastric cancer patients who received FDG-PET and an abdominal CT test prior to surgery. The results of FDG-PET and CT were compared with the surgical and pathologic results. RESULTS: The primary site detection rate of FDG-PET was 74.4%, 50.3% in early gastric cancer and 92.0% in advanced gastric cancer. Detection rate was higher when tumors were larger than 3.5 cm, had deeper depth of invasion, and at a later stage (p<0.05, respectively). In multivariate analysis, tumor size, spread of tumor cells beyond the muscle layer (> or =T2), and lymph node metastasis were statistically significant factors in primary site detection rate. The sensitivity, specificity, and positive predictive value of FDG-PET to lymph node metastasis were 59.6%, 88.8%, and 81.1% respectively, sensitivity being lower compared to CT while specificity and positive predictive value were higher. Sensitivity, specificity, and positive predictive value to distant metastasis were, respectively, 66.7%, 99.2%, and 88.0%, similar to CT. In 21 of the 392 patients (5.4%), synchronous double primary cancers were detected. CONCLUSIONS: In gastric cancer, usefullness of FDG-PET is limited to the advanced stage. Diagnostic value of this test was not superior to CT. However, FDG-PET may be useful in detecting synchronous double primary cancers.
Aged ; Female ; Fluorodeoxyglucose F18/chemistry/*diagnostic use ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Positron-Emission Tomography ; Predictive Value of Tests ; ROC Curve ; Radiopharmaceuticals/chemistry/*diagnostic use ; Retrospective Studies ; Stomach Neoplasms/*diagnosis/radionuclide imaging ; Tomography, X-Ray Computed

OBJECTIVE: In this study, there was an investigation as to whether there is a functional difference in essential tremor (ET), according to responses to beta-blockers, by evaluating regional changes in cerebral glucose metabolism. MATERIALS AND METHODS: Seventeen male patients with ET were recruited and categorized into two groups: 8 that responded to medical therapy (group A); and 9 that did not respond to medical therapy (group B). Eleven age-sex matched healthy control male subjects were also included in this study. All subjects underwent F-18 fluorodeoxyglucose (FDG)-PET, and evaluated for their severity of tremor symptoms, which were measured as a score on the Fahn-Tolosa-Marin tremor rating scale (FTM). The FDG-PET images were analyzed using a statistical parametric mapping program. RESULTS: The mean FTM score 6 months after the initiation of propranolol therapy was significantly lower in group A (18.13 > 8.13), compared with group B (14.67 = 14.67). The glucose metabolism in group A in the left basal ganglia was seen to be decreased, compared with group B. The ET showed a more significantly decreased glucose metabolism in both the fronto-temporo-occipital lobes, precuneus of right parietal lobe, and both cerebellums compared with the healthy controls. CONCLUSION: Essential tremor is caused by electrophysiological disturbances within the cortical-cerebellar networks and degenerative process of the cerebellum. Furthermore, ET may have different pathophysiologies in terms of the origin of disease according to the response to first-line therapy.
Adrenergic beta-Antagonists/*pharmacology/therapeutic use ; Aged ; Brain/*drug effects/metabolism/radiography ; Brain Mapping ; Essential Tremor/*diagnosis/drug therapy/radiography ; Fluorodeoxyglucose F18/*chemistry ; Glucose/*metabolism ; Humans ; Male ; Middle Aged ; *Positron-Emission Tomography ; Propranolol/pharmacology/therapeutic use ; Radiopharmaceuticals/*chemistry

OBJECTIVETo compare the diagnostic accuracy of (99)Tc(m)-MIBI SPECT/CT and (18)F-FDG coincidence SPECT/CT for solitary pulmonary nodules.

METHODSA total of 88 cases suspected of solitary pulmonary nodules were analyzed retrospectively, of whom 36 were examined with (18)F-FDG coincidence SPECT/CT and 52 with (99)Tc(m)-MIBI SPECT/CT. The nature of the solitary pulmonary nodules (malignant or benign) were determined according to the pathological or follow-up (>2 years) results. The diagnostic accuracy of the two modalities for solitary pulmonary nodules was evaluated by ROC curve. The correlation of the lesion size and pathological grade determined by the two modalities with the L/N ratio was assessed using Spearman correlation analysis.

RESULTS(18)F-FDG coincidence SPECT/CT and (99)Tc(m)-MIBI SPECT/CT showed a similar area under curve (AUC) of the L/N ratio (0.92 vs 0.88, P=0.565) with diagnostic sensitivities of 76.92% (20/26) and 80.77% (21/26) and specificities of 100% (10/10) and 88.46% (23/26), respectively. For solitary pulmonary nodules with lesion diameter ≤2 cm, the AUC was 1.00 with (18)F-FDG coincidence SPECT/CT and 0.90 with (99)Tc(m)-MIBI SPECT/CT (P=0.746), while for nodules beyond 2 cm but below 3 cm, the AUCs were 0.79 and 0.89, respectively (P<0.001). In either of the two modalities, correlation analysis revealed no correlation of the L/N ratio with the pathological grade of the malignant lesions (P=0.771 and 0.077, respectively). The L/N ratio was not correlated with the size of the malignant lesion detected by (99)Tc(m)-MIBI SPECT/CT (P=0.516) but was significantly correlated with the size of the malignant lesions detected by (18)F-FDG coincidence SPECT/CT (P=0.016).

CONCLUSION(99)Tc(m)-MIBI SPECT/CT has a greater diagnostic accuracy than (18)F-FDG coincidence SPECT/CT for solitary pulmonary nodules with lesion a diameter beyond 2 cm, and is therefore the primary choice for low-income patients.

Area Under Curve ; Fluorodeoxyglucose F18 ; chemistry ; Humans ; ROC Curve ; Radiopharmaceuticals ; Retrospective Studies ; Sensitivity and Specificity ; Solitary Pulmonary Nodule ; diagnostic imaging ; Technetium Tc 99m Sestamibi ; chemistry ; Tomography, Emission-Computed, Single-Photon ; Tomography, X-Ray Computed