BACKGROUNDWe previously reported that iodine-131((131)I)-labeled anti-pro-gastrin-releasing peptide (ProGRP(31-98)) monoclonal antibody D-D3 could selectively accumulate in the tumor sites of nude mice bearing small cell lung cancer (SCLC) xenografts. However, (131)I-D-D3 was cleared slowly from the body, and the best radioimmunoimaging time for SCLC was 72 - 96 hours after injection. The aims of this study were to radiolabel anti-ProGRP(31-98) D-D3 monoclonal antibody with technetium-99m ((99m)Tc) and to investigate the biodistribution of this antibody in healthy ICR mice.

METHODSD-D3 was labeled with (99m)Tc via the 2-mercaptoethanol reduction method. (99m)Tc-D-D3 was purified by the gel column separation method. The labeling efficiency and radiochemical purity were measured by thin-layer chromatography. The immunological activity of (99m)Tc-D-D3 was determined with cell conjugation assays. (99m)Tc-D-D3 was injected into healthy ICR mice via a tail vein, and all the healthy ICR mice were sacrificed by cervical dislocation at a designated time. Then, the blood and major organs were removed and weighed, and counted in a gamma scintillation counter to determine the percentage of the injected dose per gram (%ID/g).

RESULTSThe labeling rate and the radiochemical purity of (99m)Tc-D-D3 were (73.87 ± 2.89)% and (94.13 ± 4.49)%, respectively. The immunobinding rates of (99m)Tc-D-D3 to the human small cell lung cancer NCI-H446 cell line and lung adenocarcinoma A549 cell line were (81.2 ± 2.37)% and (24.3 ± 1.46)%, respectively. The distribution data of normal ICR mice demonstrated that (99m)Tc-D-D3 was mainly distributed in the liver, kidney and lung, and less in the brain tissue and muscle.

CONCLUSIONS(99m)Tc-D-D3 antibody not only had high radiochemical purity, but also had good stability both in vitro and in vivo, and maintained good immunological activity. (99m)Tc-D-D3 was metabolized mainly in the kidney and liver, and the blood radioactivity decreased rapidly. Thus, (99m)Tc-D-D3 is conducive to the radioimmunoimaging of SCLC.

Animals ; Antibodies, Monoclonal ; chemistry ; immunology ; metabolism ; Female ; Male ; Mice ; Mice, Inbred ICR ; Peptide Fragments ; immunology ; Recombinant Proteins ; immunology ; Technetium ; chemistry

BACKGROUNDTechnetium-99m or (99m)Tc is widely used for labeling peptide in nuclear medicine. Somatostatin and its analog can inhibit tumor cell growth after binding with its receptor. This research was to study the preclinical effect of a new (99m)Tc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-depreotide, indirect (99m)Tc labeling of depreotide using HYNIC as a bifunctional chelator.

METHODSThe cyclopeptide, cyclo-[(N-Me) Phe-Tyr-D-Trp-Lys-Val-Hcy], the linear peptide, and [ClCH(2)-CO×b-Dap-Lys- Cys-Lys×amide] were synthesized by Fmoc solid-phase synthesis. The cyclopeptide and the linear peptide were linked by liquid-phase synthesis. The product depreotide was isolated and purified by high performance liquid chromatography and was confirmed by mass spectrography. Depreotide was labeled with (99m)Tc through a direct labeling method, using HYNIC as a bifunctional chelator. Paper chromatography method was used to calculate the labeling rate, and through the comparative analysis selected the best mark conditions. The new (99m)Tc-HYNIC-depreotide was tested by high-performance liquid chromatography (HPLC). The internalization and externalization rates of the new (99m)Tc-HYNIC-depreotide were studied in A549 cells. Furthermore, biodistribution of the radiopeptide was studied in nude mice, bearing tumors from human lung carcinoma cells SPC-A1.

RESULTSThe molecular of synthesize depreotide was 1358, and the purity of it was 95.29%. The labeling efficiency of (99m)Tc-HYNIC-depreotide was highest at pH 6.0 and 15°C, about (70.95 ± 0.84)%. The labeling rate of the new (99m)Tc-HYNIC-depreotide rose to a peak of (20.75 ± 0.48)% at 60 minutes in A549 cells at 37°C and decreased slightly later, while it elevated gradually during the time course at 4°C and 25°C. The internalization rate of the new (99m)Tc-HYNIC-depreotide at 37°C increased gradually and reached the peak of 84.4% in 120 minutes, while the externalization rate of the new (99m)Tc-HYNIC-depreotide was always less than 20%. In mice bearing the experimental SPC-A1 tumor, the new (99m)Tc-HYNIC-depreotide demonstrated a high tumor uptake of (4.05 ± 0.04)% ID/g at 1.5 hpi and remained high ((2.51 ± 0.06)% ID/g) at 4 hpi. The tumor-to-lung activity concentration ratio (T/Lu) was very high for the new (99m)Tc-HYNIC-depreotide at all time points. So did the tumor-to-muscle activity (T/Mu) and tumor-to-blood activity concentration ratios (T/Bl).

CONCLUSIONThe findings suggested that the new (99m)Tc-HYNIC-depreotide might be a promising candidate radiopharmaceutical for imaging somatostatin receptor positive lung cancer.

Animals ; Cell Line, Tumor ; Humans ; Hydrazines ; chemistry ; Lung Neoplasms ; metabolism ; pathology ; Male ; Mice ; Mice, Nude ; Nicotinic Acids ; chemistry ; Receptors, Somatostatin ; metabolism ; Technetium ; chemistry

Primary intraosseous arteriovenous malformations (AVMs) are rare and have only been occasionally reported. We herein report a histologically proven case of primary intraosseous AVM in the tibia, which mimicked a fibrous tumour on radiography. This presentation carries a risk of triggering acute large haemorrhage through unnecessary biopsy. In intraosseous AVM, the magnetic resonance (MR) imaging features typical of a soft tissue AVM are absent, making diagnosis difficult. In this report, peculiar MR features in the presence of a connecting vessel between the normal deep venous system of the lower extremity and the tumour provide a clue for the early diagnosis of primary intraosseous AVM.
Arteriovenous Malformations ; diagnostic imaging ; physiopathology ; Biopsy ; Contrast Media ; chemistry ; Female ; Hemorrhage ; Humans ; Magnetic Resonance Imaging ; Pain ; Radiography ; Technetium ; chemistry ; Tibia ; physiopathology ; Whole Body Imaging ; Young Adult

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 evaluate the clinical value of (99m)Tc-Pingyangmycin (PYM) imaging for the diagnosis of primary lung cancer.

METHODSRadionuclide (99m)Tc-Pingyangmycin (PYM) imaging was performed in 56 patients with pulmonary lesions.

RESULTSThe uptake ratio and retention index (RI) were different in malignant and benign lesions. With the delayed ratio regarded as the threshold for lung cancer, the overall accuracy, sensitivity and specificity of (99m)Tc-PYM in the diagnosis of lung cancer were 82.1%, 82.7% and 80%, respectively. If RI was regarded as the threshold, the overall accuracy, sensitivity and specificity were 94.6%, 93% and 100%, respectively. There was no significant difference among different histological types of the lung carcinoma.

CONCLUSION(99m)Tc-PYM, as a good imaging agent, is useful in differentiating malignant lung lesions from benign ones.

Adult ; Bleomycin ; analogs & derivatives ; chemistry ; Female ; Humans ; Lung Neoplasms ; diagnosis ; diagnostic imaging ; Male ; Middle Aged ; Technetium ; Tomography, Emission-Computed, Single-Photon

The aim of this study was to ascertain the folate receptor (FR) targetability by an in vitro study and to acquire FR-targeted images in vivo models by using synthetic folate conjugates. PEG-folate was synthesized and labeled with (99m)Tc and fluorescein isothiocynate (FITC). Cell uptake studies were carried out in KB cells (FR-positive) and A549 cells (FR-negative) using FITC- and the (99m)Tc-labeled conjugates. The radiolabeled conjugate was intravenously injected to KB tumor xenografted mice. After it was injected, gamma images were recorded at 30 min, 1, 2, 3 and 4 hr. Cell uptake studies showed a difference between the KB cells and the A549 cells by flow cytometry analysis and gamma counting. On in vivo images, the tumor-tonormal muscle ratio was greater than 4. It ascertained that the PEG-folate conjugate specifically binds to the FR expressed on tumor cells in vitro. Moreover, it was possible to acquire the FR-targeted gamma images using PEG-folate conjugates in tumor models.
Animals ; Carrier Proteins/*metabolism ; Cell Line, Tumor ; Female ; Fluorescein-5-isothiocyanate/pharmacology ; Folic Acid/*metabolism ; Humans ; Image Processing, Computer-Assisted ; Mice ; Mice, Nude ; Microscopy, Fluorescence ; Neoplasm Transplantation ; Polyethylene Glycols/*chemistry ; Receptors, Cell Surface/*metabolism ; Technetium/*chemistry ; Time Factors

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

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

OBJECTIVETo prepare (99m)Tc-labeled Anti-VEGF mAb 5-FU loaded polylactic acid nanoparticles ((99m)Tc-Ab-5-FU-NPs) and investigate its biodistribution in human gastric carcinoma xenografts.

METHODS(99m)Tc-Ab-5-FU-NPs were prepared by labeling Ab-5-FU-NPs with (99m)Tc using improved Schwarz method. After isolation of (99m)Tc-Ab-5-FU-NPs using SephadexG250 column, the labeling ratio and radiochemical purity were determined using chromatography. The immunocompetence of (99m)Tc- Ab-5-FU-NPs was detected by ELISA and immunohistochemistry. (99m)Tc-Ab-5-FU-NPs were then injected via the tail vein into SCID mice bearing human gastric carcinoma, and (99m)Tc labeled mice-derived monoclonal IgG loaded polylactic acid nanoparticles were used as the control, followed by radioimmunoscintigraphic imaging at 2 and 6 h. The radioactive count and radioactive ratio of the tumor and non-tumor tissue (T/NT) in the animal models were calculated using ROI technique. After imaging at 24 h, SCID mice were sacrificed and the radioactive distribution, the %ID/g, as well as the T/NT radioactive ratio were examined, respectively. The concentrations of 5-FU in the tumor and blood were also detected using HPLC method.

RESULTSThe labeling ratio of (99m)Tc-Ab-5-FU-NPs was 90%-95%. (99m)Tc-Ab-5-FU-NPs were detected in the tumor tissues by radioimmunoimaging 2 h after the injection. ID%/g in the tumor tissues at 2 and 6 h were both significantly higher than that of the control group. Both the ID%/g in tumor tissues and radioactive ratio of tumor and blood at 6 h were higher than those at 2 h, and the concentration of 5-FU in experimental group increased continuously with time and was significantly higher than that in control group.

CONCLUSIONS(99m)Tc-Ab-5-FU-NPs prepared in this study can meet the demands of radioimmunoimaging, and the anti-VEGF monoclonal antibody possesses reliable immune targeting ability. Six hours after injection, (99m)Tc-Ab-5-FU-NPs can specifically accumulate in the tumor tissues in human gastric carcinoma xenografts at high concentration.

Animals ; Antibodies, Monoclonal ; chemistry ; immunology ; Cell Line, Tumor ; Cell Transformation, Neoplastic ; Female ; Fluorouracil ; blood ; chemistry ; pharmacokinetics ; Humans ; Lactic Acid ; chemistry ; Male ; Mice ; Mice, SCID ; Nanoparticles ; Polyesters ; Polymers ; chemistry ; Radioimmunotherapy ; Stomach Neoplasms ; blood ; metabolism ; pathology ; radiotherapy ; Technetium ; chemistry ; Vascular Endothelial Growth Factor A ; immunology

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