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 aim of this study was to estimate internal radiation doses and lifetime cancer risk from food ingestion. Radiation doses from food intake were calculated using the Korea National Health and Nutrition Examination Survey and the measured radioactivity of 134Cs, 137Cs, and 131I from the Ministry of Food and Drug Safety in Korea. Total number of measured data was 8,496 (3,643 for agricultural products, 644 for livestock products, 43 for milk products, 3,193 for marine products, and 973 for processed food). Cancer risk was calculated by multiplying the estimated committed effective dose and the detriment adjusted nominal risk coefficients recommended by the International Commission on Radiation Protection. The lifetime committed effective doses from the daily diet are ranged 2.957-3.710 mSv. Excess lifetime cancer risks are 14.4-18.1, 0.4-0.5, and 1.8-2.3 per 100,000 for all solid cancers combined, thyroid cancer, and leukemia, respectively.
Adolescent ; Adult ; Cesium Radioisotopes/chemistry ; Child ; Child, Preschool ; *Eating ; Food Contamination, Radioactive/*analysis ; Humans ; Infant ; Infant, Newborn ; Iodine Radioisotopes/chemistry ; Neoplasms, Radiation-Induced/*etiology ; Nutrition Surveys ; Radiation Dosage ; Republic of Korea ; Young Adult

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

Iodine-131 is a radioisotope that is routinely used for the treatment of differentiated thyroid cancer after total or near-total thyroidectomy. However, there is some evidence that iodine-131 can induce liver injury . Here we report a rare case of drug-induced liver injury (DILI) caused by iodine-131 in a patient with regional lymph node metastasis after total thyroidectomy. A 47-year-old woman was admitted with elevated liver enzymes and symptoms of general weakness and nausea. Ten weeks earlier she had undergone a total thyroidectomy for papillary thyroid carcinoma and had subsequently been prescribed levothyroxine to reduce the level of thyroid-stimulating hormone. Eight weeks after surgery she underwent iodine-131 ablative therapy at a dose of 100 millicuries, and subsequently presented with acute hepatitis after 10 days. To rule out all possible causative factors, abdominal ultrasonography, endoscopic ultrasonography (on the biliary tree and gall bladder), and a liver biopsy were performed. DILI caused by iodine-131 was suspected. Oral prednisolone was started at 30 mg/day, to which the patient responded well.
Abdomen/diagnostic imaging ; Chemical and Drug Induced Liver Injury/*diagnosis/drug therapy ; Female ; Humans ; Iodine Radioisotopes/chemistry ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Middle Aged ; Prednisolone/therapeutic use ; Thyroid Neoplasms/drug therapy/surgery ; Thyroidectomy ; Thyroxine/therapeutic use ; Ultrasonography

Although the prognosis of patients with differentiated thyroid carcinoma (DTC) is generally encouraging, a diagnostic dilemma is posed when an increasing level of serum thyroglobulin (Tg) is noted, without detection of a recurrent tumor using conventional imaging tools such as the iodine-131 whole-body scanning (the [131I] scan) or neck ultrasonography (US). The objective of the present study was to evaluate the diagnostic value of [124I]-PET/CT and [18F]-FDG-PET/CT in terms of accurate detection of both iodine- and non-iodine-avid recurrence, compared with that of conventional imaging such as the [131I] scan or neck ultrasonography (US). Between July 2009 and June 2010, we prospectively studied 19 DTC patients with elevated thyroglobulin levels but who do not show pathological lesions when conventional imaging modalities are used. All involved patients had undergone total thyroidectomy and radioiodine (RI) treatment, and who had been followed-up for a mean of 13 months (range, 6-21 months) after the last RI session. Combined [18F]-FDG-PET/CT and [124I]-PET/CT data were evaluated for detecting recurrent DTC lesions in study patients and compared with those of other radiological and/or cytological investigations. Nine of 19 patients (47.4%) showed pathological [18F]-FDG (5/19, 26.3%) or [124I]-PET (4/19, 21.1%) uptake, and were classed as true-positives. Among such patients, disease management was modified in six (66.7%) and disease was restaged in seven (77.8%). In particular, the use of the described imaging combination optimized planning of surgical resection to deal with locoregional recurrence in 21.1% (4/19) of patients, who were shown to be disease-free during follow-up after surgery. Our results indicate that combination of [18F]-FDG-PET/CT and [124I]-PET/CT affords a valuable diagnostic method that can be used to make therapeutic decisions in patients with DTC who are tumor-free on conventional imaging studies but who have high Tg levels.
Adult ; Aged ; Aged, 80 and over ; Carcinoma/metabolism/*radionuclide imaging/surgery ; Female ; Fluorodeoxyglucose F18/chemistry/diagnostic use ; Follow-Up Studies ; Humans ; Iodine Radioisotopes/chemistry/diagnostic use ; Male ; Middle Aged ; Neck/ultrasonography ; Positron-Emission Tomography and Computed Tomography ; Prospective Studies ; Radiopharmaceuticals/chemistry/*diagnostic use ; Recurrence ; Thyroglobulin/blood ; Thyroid Neoplasms/metabolism/*radionuclide imaging/surgery ; Thyroidectomy ; Whole Body Imaging

Proteins of the complement system are known to interact with many charged substances. We recently characterized binding of C1q and factor H to immobilized and liposomal anionic phospholipids. Factor H inhibited C1q binding to anionic phospholipids, suggesting a role for factor H in regulating activation of the complement classical pathway by anionic phospholipids. To extend this finding, we examined interactions of C1q and factor H with lipid A, a well-characterized activator of the classical pathway. We report that C1q and factor H both bind to immobilized lipid A, lipid A liposomes and intact Escherichia coli TG1. Factor H competes with C1q for binding to these targets. Furthermore, increasing the factor H: C1q molar ratio in serum diminished C4b fixation, indicating that factor H diminishes classical pathway activation. The recombinant forms of the Cterminal, globular heads of C1q A, B and C chains bound to lipid A and E. coli in a manner qualitatively similar to native C1q, confirming that C1q interacts with these targets via its globular head region. These observations reinforce our proposal that factor H has an additional complement regulatory role of down-regulating classical pathway activation in response to certain targets. This is distinct from its role as an alternative pathway down-regulator. We suggest that under physiological conditions, factor H may serve as a downregulator of bacterially-driven inflammatory responses, thereby fine-tuning and balancing the inflammatory response in infections with Gram-negative bacteria.
Binding, Competitive ; immunology ; Complement Activation ; immunology ; Complement C1q ; chemistry ; immunology ; metabolism ; Complement C4b ; analysis ; Complement Factor H ; chemistry ; immunology ; metabolism ; Complement Pathway, Classical ; immunology ; Escherichia coli ; immunology ; metabolism ; Humans ; Iodine Radioisotopes ; Isotope Labeling ; Lipid A ; immunology ; metabolism ; Liposomes ; immunology ; metabolism ; Protein Binding ; immunology ; Recombinant Proteins ; chemistry ; immunology ; metabolism ; Substrate Specificity

VPAC2 is a co-receptor of pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) and mediates multiple bio-functions. In order to construct the CHO line expressing VPAC2 stably, pcDNA-VPAC2 was used to transfect CHO cells. The positive clones were selected by G418 and the clone VPAC2-CHO with high sensitivity to PACAP38 was picked out by its ability to promoting the concentration of cAMP. RT-PCR, Western blot and Immunofluorescenece assay were used to identify the express of VPACS. Binding competition with VPAC2 agonist and the bioactivity of mediating the ligand to promote the concentration of cAMP showed that VPAC2 was expressed effectively in VPAC2-CHO. The results of Scatchard analysis revealed that VAPC2-CHO expressed a receptor density of (1.1 +/- 0.2) pmol/mg protein, respectively, with Kd values of (0.55 +/- 0.10) nmol/L for PACAP38 used as a tracer. The construction of CHO cells expressing VPAC2 specially and functionally lays a foundation not only for the further research on the characters and functions of VPAC2 but also for the screening and characterization of novel agonists of antagonists for VPAC2.
Animals ; Binding, Competitive ; CHO Cells ; Cell Membrane ; drug effects ; metabolism ; Cricetinae ; Cricetulus ; Cyclic AMP ; metabolism ; Gene Expression ; Genetic Vectors ; genetics ; Iodine Radioisotopes ; chemistry ; Pituitary Adenylate Cyclase-Activating Polypeptide ; chemistry ; metabolism ; pharmacology ; Receptors, Vasoactive Intestinal Peptide, Type II ; agonists ; antagonists & inhibitors ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection

Precisely locating tumors always proves to be difficult. To find a molecule that can specifically bind to tumor cells is the key. Recently, chlorotoxin (CTX) has been proved to be able to bind to many kinds of tumor cells. The CTX receptor on the cell surface has been demonstrated to be matrix metalloproteinase-2 (MMP-2). Many researchers have combined CTX with other molecules, including 131I, Cy5.5, iron oxide nanoparticles coated by polyethylene glycol (NP-PEG), and so on, and thus synthesized various types of probes that can be detected by gamma-camera, single photon emission computed tomography (SPECT) or magnetic resonance imaging (MRI). With these methods, the binding degree of CTX could be assessed. These studies demonstrated that CTX has a highly specific binding ability, high stability, and security. CTX could also inhibit or kill the tumor cells. A nonviral nanovector has been developed for gene therapy. As a result, it gradually develops into a new method of diagnosis and targeted therapy of tumors. This article reviews the current progress on CTX including the origin, chemical construction, the mechanism of binding with tumor cells, and the application to tumor imaging diagnosis and therapy.
Brain Neoplasms ; diagnosis ; genetics ; therapy ; Carbocyanines ; metabolism ; Chloride Channels ; drug effects ; Diagnostic Imaging ; methods ; Ferric Compounds ; metabolism ; Genetic Therapy ; Glioma ; diagnosis ; genetics ; therapy ; Humans ; Iodine Radioisotopes ; Magnetic Resonance Imaging ; Matrix Metalloproteinase 2 ; metabolism ; Nanoparticles ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Polyethylene Glycols ; chemistry ; Scorpion Venoms ; chemistry ; metabolism ; Tomography, Emission-Computed, Single-Photon

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and it has a poor prognosis and few therapeutic options. Radiotherapy is one of the most effective forms of cancer treatment, and P53 protein is one of the key molecules determining how a cell responds to radiotherapy. The aim of this study was to determine the therapeutic efficacy of iodine-131 in three human HCC cell lines. METHODS: Western blotting was used to measure P53 expression. The effects of radiotherapy with iodine-131 were assessed by using the clonogenic assay to evaluate cell survival. Flow cytometry was carried out to examine the effects of iodine-131 on cell death, oxidative stress, reduced intracellular glutathione expression, the mitochondrial membrane potential, and the cell cycle. RESULTS: The P53 protein was not expressed in Hep3B2.1-7 cells, was expressed at normal levels in HepG2 cells, and was overexpressed in HuH7 cells. P53 expression in the HuH7 and HepG2 cell lines increased after internal and external irradiation with iodine-131. Irradiation induced a decrease in cell survival and led to a decrease in cell viability in all of the cell lines studied, accompanied by cell death via late apoptosis/necrosis and necrosis. Irradiation with 131-iodine induced mostly cell-cycle arrest in the G0/G1 phase. CONCLUSIONS: These results suggest that P53 plays a key role in the radiotherapy response of HCC.
Apoptosis/*radiation effects ; Blotting, Western ; Carcinoma, Hepatocellular/metabolism/pathology/radiotherapy ; Cell Line, Tumor ; Cell Survival/drug effects ; G1 Phase Cell Cycle Checkpoints/radiation effects ; *Gamma Rays ; Glutathione/metabolism ; Hep G2 Cells ; Humans ; Iodine Radioisotopes/chemistry/pharmacology/therapeutic use ; Liver Neoplasms/metabolism/pathology/radiotherapy ; Phosphorylation ; Reactive Oxygen Species/metabolism ; Tumor Suppressor Protein p53/*metabolism

We aimed to determine the characteristic adverse events (AEs) of iodinated contrast media (IOCM) and to compare the safety profiles of different IOCM. This study used the database of AEs reports submitted by healthcare professionals from 15 Regional Pharmacovigilance Centers between June 24, 2009 and December 31, 2010 in Korea. All reports of IOCM, including iopromide, iohexol, iopamidol, iomeprol, ioversol, iobitridol and iodixanol, were analyzed. Safety profiles were compared between different IOCM at the system organ level using the proportional reporting ratio (PRR) and 95% confidence interval (95% CI). Among a total of 48,261 reports, 6,524 (13.5%) reports were related to the use of IOCM. Iopromide (45.5%), iohexol (16.9%), iopamidol (14.3%) and iomeprol (10.3%) were identified as frequently reported media. 'Platelet, bleeding & clotting disorders' (PRR, 29.6; 95%CI, 1.9-472.6) and 'urinary system disorders' (PRR, 22.3; 95% CI, 17.1-29.1) were more frequently reported for iodixanol than the other IOCM. In conclusion, the frequency of AEs by organ class was significantly different between individual media. These differences among different IOCM should be considered when selecting a medium among various IOCM and when monitoring patients during and after its use to ensure optimum usage and patient safety.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Blood Platelet Disorders/chemically induced ; Child ; Child, Preschool ; Contrast Media/*adverse effects/diagnostic use ; Databases, Factual ; Female ; Humans ; Infant ; Infant, Newborn ; Iodine Radioisotopes/chemistry ; Male ; Middle Aged ; Neoplasms/radionuclide imaging ; Radiopharmaceuticals/*adverse effects/diagnostic use ; Urologic Diseases/chemically induced ; Young Adult