OBJECTIVETo compare the uptake of four contrast agents: (99)Tc(m)-RGD-4CK, (99)Tc(m)-N(NOET)(2), (99)Tc(m)-MIBI and (18)F-FDG in Bal B/c nude mice bearing human non-small cell lung cancer NCI-H358 and evaluate their diagnostic value in low-metabolic lung cancer.

METHODSHuman bronchioloalveolar carcinoma NCI-H358 cells were subcutaneously inoculated in Bal B/c nude mice to establish mouse models bearing human lung cancer. Twenty tumor-bearing nude mice were given injection of the four contrast agent, respectively, 5 mice in each group. SPECT imaging and biodistribution of the 4 tracers in the tumor-bearing nude mice were performed. The ratios of tumor to non-tumor (T/NT) of the tracers were compared.

RESULTSThe results from semi-quantification of the planar image and assessment of biodistribution showed that tumor to contralateral muscle activity ratios (T/NT) of the four tracers had statistically significant difference between each two of the four tracer groups of tumor-bearing mice (P < 0.001), with a highest value of T/NT ratio in the (99)Tc(m)-RGD-4CK group.

CONCLUSIONSNCI-H358 tumors show a higher uptake of (99)Tc(m)-RGD-4CK than (18)F-FDG. It suggests that when diagnosing a well-differentiated lung cancer such as bronchioloalveolar carcinoma, the contrast agent (99)Tc(m)-RGD-4CK may be more sensitive than (18)F-FDG, and it may become a promising contrast agent in tumor imaging diagnosis.

Animals ; Carcinoma, Non-Small-Cell Lung ; diagnostic imaging ; metabolism ; pathology ; Cell Line, Tumor ; Contrast Media ; pharmacokinetics ; Female ; Fluorodeoxyglucose F18 ; pharmacokinetics ; Humans ; Lung Neoplasms ; diagnostic imaging ; metabolism ; pathology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Oligopeptides ; pharmacokinetics ; Organotechnetium Compounds ; pharmacokinetics ; Radiopharmaceuticals ; pharmacokinetics ; Technetium Tc 99m Sestamibi ; pharmacokinetics ; Thiocarbamates ; pharmacokinetics ; Tissue Distribution ; Tomography, Emission-Computed, Single-Photon ; methods

BACKGROUND AND OBJECTIVEPET/CT imaging is expensive, so searching the tumor imaging agent for SPECT/CT is necessary. 99Tc(m) -N(NOEt)2 [bis (N-ethoxy-N-ethyl dithiocarbamato) nitrido 99Tc(m) (V)] can be uptaken by lung cancer cells and other cells alike. The aim of this study is to evaluate the distinctive value in lung tumor with 99Tc(m) -N(NOEt)2, the difference in its uptake kinetics in human embryonic lung diploid fibroblasts KMB17 and several kinds of lung cancer cells lines.

METHODSFirstly, six different cell culture medium which contained YTMLC Gejiu human lung squamous carcinoma cell, SPC-A1 human lung adenocarcinoma cell, AGZY low metastatic human lung adenocarcinoma, 973 high metastatic human lung adenocarcinoma cell, GLC-82 Gejiu human lung adenocarcinoma cell, and KMB17 human embryonic lung diploid fibroblast, respectively with equal cell density of 1 x 10(6)/mL and the same volume were prepared; secondly, the same radioactive dose of 99Tc(m) -N(NOEt)2 was added into each sample and then 300 microL mixed sample was taken out respectively and cultured in 37 degrees C culture box; Finally, 5 min, 15 min, 30 min, 45 min, 60 min, 75 min, 90 min after cultivation, centrifuged each cultured sample and determined the intracellular radiocounts of each sample, calculated each cell sample's uptake rate of 99Tc(m) -N(NOEt)2 at different time.

RESULTSStatistical difference was found among six cell samples, and the uptake rate sequence from high to low is 973 and SPC-A1 > YTMLC > GLC-82 > AGZY > KMB17 respectively; furthermore, 30 min-45 min after culture, the uptake rate reached stability, and the 45 min uptake rate of each sample was higher than its 96.7% uptake peak.

CONCLUSIONBased on the results above mentioned, it is supposed that there are discriminative clinical value when using 99Tc(m) -N(NOEt)2 as a tumor targeting imaging agent, and 30 min or so after injection may be the best imaging time in the early imaging stage.

Cell Line ; Cell Line, Tumor ; Contrast Media ; pharmacokinetics ; Fibroblasts ; cytology ; metabolism ; Humans ; Lung Neoplasms ; metabolism ; Organotechnetium Compounds ; pharmacokinetics ; Tomography, Emission-Computed, Single-Photon

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 synthesize the complex fac-[⁹⁹(m)Tc(CO)₃(H₂O)₃](+) for labeling IgG and investigate the in vitro stability of ⁹⁹(m)Tc(CO)₃(H₂O)₃-IgG and its biodistribution in mice.

METHODSfac-[⁹⁹(m)Tc(CO)₃(H₂O)₃](+) was synthesized and its radiochemical purity determined using polyamide membrane chromatography. IgG was directly labeled with fac-[⁹⁹(m)Tc(CO)₃(H₂O)₃](+) and the labeling ratio was determined using chromatography. The stability of ⁹⁹(m)Tc(CO)₃(H₂O)₃-IgG in human serum albumin and normal saline was evaluated. ⁹⁹(m)Tc(CO)₃(H₂O)₃-IgG was injected via the tail vein into 9 mice at the dose of 3.7×10⁴ Bq/100 µl, and SPECT image was obtained at 2, 4 and 12 h after the injection. The mice were sacrificed at these time points to measure the radioactivity and calculate the %ID/g in each organ.

RESULTSFac-[⁹⁹(m)Tc(CO)₃(H₂O)₃](+) had a radiochemical purity of 82.48% and remained stable in vitro at room temperature within 4 h. The labeling ratio of ⁹⁹(m)Tc(CO)₃(H₂O)₃-IgG was 57.04% with a radiochemical purity exceeding 90%. In the solution of human serum albumin, the labeled IgG maintained a stable radiochemical purity, but in normal saline, its radiochemical purity was lowered to 20% at 24 h. After injection in mice, the labeled IgG was deposited mainly in the liver, spleen, kidneys, and the blood pool showed a sustained radioactivity.

CONCLUSION⁹⁹(m)Tc(CO)₃(H₂O)₃-IgG prepared in this study has good stability in vitro and in vivo in 24 h and shows a biodistribution pattern similar to that of IgG protein in vivo. The intermediate fac-[⁹⁹(m)Tc(CO)₃(H₂O)₃](+) can meet the experimental requirement for labeling monoclonal antibodies and polypeptides.

Animals ; Immunoglobulin G ; administration & dosage ; metabolism ; Mice ; Mice, Inbred Strains ; Organotechnetium Compounds ; pharmacokinetics ; Radiopharmaceuticals ; pharmacokinetics ; Tissue Distribution

BACKGROUNDBacterial infection can pose a substantial diagnostic dilemma. (99m)Tc-labeled ciprofloxacin (CPF) was developed as a biologically active radiopharmaceutical to diagnose infection. In the present research, we studied the biodistribution and imaging properties of infection tracer (99m)Tc-CPF in a mouse model of infection.

METHODSCPF was labeled with (99m)Tc and the radiochemical purity and labeling rate were measured. A mouse model of infection was established. We then determined the biodistribution of (99m)Tc-CPF and conducted the whole body scintigraphy of the animal model.

RESULTS(99m)Tc-Ciprotech was stable for at least 6 hours at room temperature. The labeling rate of CPF by (99m)Tc was over 90%. Clearance of radioactivity mainly occurred in the liver and kidney, and the clearance from blood was rapid. Both biodistribution and imaging results showed higher uptake of (99m)Tc-CPF at sites of infection. The infectious tissue/normal tissue ratio peak was 4.30 at 4 hours after injection.

CONCLUSIONS(99m)Tc-CPF is a sensitive radiopharmaceutical for scintigraphy of infectious lesions and it is easy to prepare.

Animals ; Anti-Infective Agents ; chemistry ; pharmacokinetics ; Bacterial Infections ; diagnosis ; Ciprofloxacin ; chemistry ; pharmacokinetics ; Disease Models, Animal ; Isotope Labeling ; methods ; Mice ; Mice, Inbred BALB C ; Organotechnetium Compounds ; chemistry ; Tissue Distribution

OBJECTIVETo prepare 99Tcm-annexinV and evaluate its application in the early prediction of therapeutic effect of chemical agent on lung cancer.

METHODSAnnexin V was obtained by recombinant pichia pastoris expression, ammonium sulfate precipitation, and size-exclusion chromatography. The purified protein was labeled with 99Tc(m) at the N-terminal site by stannous chloride reduction and purified by desalting. The labeling yield and radiochemical purity of 99Tc(m)-annexinV were determined by instant thin-layer chromatography. The biological activity of 99Tc(m)-annexinV was tested by phosphatidylserine-exposed erythrocytes bound radioactivity counting. The lung cancer mice models were established by inoculating LA795 cells to right flank of 615 mice subcutaneously and tumor tissue transplantation. The biodistribution of 99Tc(m)-annexinV in lung cancer mice models were investigated at 6, 12, 24, and 48 h after cyclophosphamide administration.

RESULTSThe annexin V was secreted from pichia pastoris and purified by ammonium sulfate precipitation and size-exclusion chromatography with high yield. The annexin V could be labeled at room temperature with 50.2% radioactivity yield. The radiochemical purity of 99Tc(m)-annexinV reached up to 93.9% with intact biological activity. The biodistribution analysis demonstrated that 99Tc(m)-annexinV was excreted from kidney. The uptake of 99Tc(m)-annexinV at tumor reached maximum 48 h after cyclophosphamide administration while tumor to muscle ratio was 6.34 and tumor to blood ratio was 4.09.

CONCLUSIONS99Tc(m)-annexinV derived from pichia pastoris was successfully prepared. It is useful in predicting the therapeutic effect of chemical agent on lung cancer.

Animals ; Annexin A5 ; administration & dosage ; pharmacokinetics ; Cell Line, Tumor ; Disease Models, Animal ; Drug Monitoring ; methods ; Female ; Humans ; Lung Neoplasms ; drug therapy ; metabolism ; Male ; Mice ; Organotechnetium Compounds ; administration & dosage ; pharmacokinetics ; Tissue Distribution

OBJECTIVETo investigate the feasibility of regional lymph nodes targetting with enrichment of radioactive 99mTc-polyphase liposome of 5-fluorouracil (99mTc-FL, FL).

METHODS18 rabbits were randomly divided into 3 groups, 6 rabbits per group. All rabbits were injected hypodermally with of 99mTc-FL in the right and left big toe webs, 18.5 MBq each side. The post-injection interval was 3 h in group 1, 6 h in group 2, and 8 h in group 3. The radioactivity was examined in the resected local lymph nodes, non-draining lymph nodes, liver, spleen, kidney, heart, lung, intestines, and in blood and urine.

RESULTSThe radioactive isotope uptake percentage (%) was 2.32 +/- 0.75 in group 1, 5.37 +/- 1.73 in group 2, 8.61 +/- 1.89 in group 3. The radioactive isotope uptake percentage (%) per gram in local lymph nodes was significantly different between each two groups among the 3 groups (P < 0.05). The ratios of x of regional lymph nodes/non-draining lymph nodes, regional lymph nodes/blood, regional lymph nodes/urine, regional lymph nodes/liver, regional lymph nodes/spleen, regional lymph nodes/kidney, regional lymph nodes/heart, regional lymph nodes/lung, regional lymph nodes/intestine in group 1 were 232.00, 16.57, 23.20, 29.00, 19.33, 25.78, 46.40, 46.40 and 25.78, respectively. The ratios in group 2 were 89.50, 41.31, 18.52, 67.13, 41.31, 25.57, 134.25, 59.67 and 59.67, respectively. The ratios in group 3 were 86.10, 61.50, 16.56, 53.81, 57.40, 10.01, 107.63, 107.63 and 86.10, respectively. The differences of radioactive isotope uptake percentage were statistically significant (P < 0.01) between regional lymph nodes and other organs, i. e. non-draining lymph nodes, blood, urine, liver, spleen, kidney, heart, lung and intestine per gram in each group.

CONCLUSIONThe radioactive 99mTc-FL may slowly flow into regional lymphatic chains rather than directly enter blood circulation. So 99mTc-FL can be highly accumulated in the local lymph nodes. This regional lymph nodes targetting with enrichment of radioactive 99mTc-FL evidently indicates the feasibility of regional lymph system chemotherapy for pulmonary malignancies.

Animals ; Female ; Fluorouracil ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Heart ; diagnostic imaging ; Intestines ; diagnostic imaging ; Kidney ; diagnostic imaging ; Liposomes ; Liver ; diagnostic imaging ; Lung ; diagnostic imaging ; Lymph Nodes ; diagnostic imaging ; Male ; Organotechnetium Compounds ; administration & dosage ; pharmacokinetics ; Rabbits ; Radionuclide Imaging ; Random Allocation ; Spleen ; diagnostic imaging

OBJECTIVETo evaluate if 99mTc-HYNIC-annexin V may be used to detect the early chemotherapeutic effect and to determine the best timing for detecting apoptosis in vivo.

METHODSAnnexin V was labeled with 99mTc using HYNIC as a bifunctional agent. Normal Kunming mice received inoculation of Ehrlich ascites cells into the right upper limb. After the tumor reached 1 cm in diameter, the mice were randomly divided into saline treatment group as control and cyclophosphamide (150 mg/kg injected intraperitoneally) treatment group. 99mTc-HYNIC-annexin V was injected intravenously at 1 h and 24 h after treatment. Region of interest technique (ROI) from the SPECT images taken at different time was used to get the ratio of tumor/limb in each group. TUNEL staining was used to detect apoptotic cells and the rates of positive stained cells were calculated.

RESULTSAfter treatment with saline, only little amount of the radiolabeled tracer could be seen in the tumor and showed weak image of the tumor. But after 24 h of treatment with cyclophosphamide, clear image on the tumor could be seen. 24 h after the treatment of cyclophosphamide, the ratio of tumor/limb was (6.27 +/- 0.24) which was much higher than that at 24 h after treatment with saline (2.36 +/- 0.18) and that at 1 h after cyclophosphamide treatment (4.00 +/- 0.38). At 24 h after cyclophosphamide treatment, TUNEL staining showed a significantly higher rate of apoptotic cells in the mice.

CONCLUSION99mTc-HYNIC-annexin V can be used as an apoptosis-imaging agent to detect and evaluate the early curative effect after chemotherapy. The effective detection of apoptotic response in tumor with 99mTc-HYNIC-annexin V requires a 24 h interval after chemotherapy. SPECT images can be obtained at 60 min after injection of the imaging agent. It suggests that 99mTc-HYNIC-annexin V may become a promising agent for apoptosis-imaging in clinical application.

Animals ; Annexin A5 ; pharmacokinetics ; Antineoplastic Agents, Alkylating ; therapeutic use ; Apoptosis ; drug effects ; Carcinoma, Ehrlich Tumor ; diagnostic imaging ; drug therapy ; pathology ; Cyclophosphamide ; therapeutic use ; Male ; Mice ; Neoplasm Transplantation ; Organotechnetium Compounds ; pharmacokinetics ; Radiopharmaceuticals ; pharmacokinetics ; Random Allocation ; Tissue Distribution ; Tomography, Emission-Computed, Single-Photon

OBJECTIVETo study the safety, biodistribution, and dosimetry of myocardial perfusion imaging agent 99Tc(m)N-NOET in 10 healthy volunteers.

METHODS744-792 MBq of 99Tc(m)N-NOET was injected to each volunteer. Safety parameters and adverse event was measured in 24 hours of injection. Biodistribution was studied by whole-body imaging 1, 30 minutes, 1, 2, 4, 8, and 24 hours after the injection of 99Tc(m)N-NOET. The estimation of dosimetry was based on the standard medical internal radiation dose method using MIRDOSE 3.0 analysis program. Myocardial single photon emission computed tomography (SPECT) imaging was performed at 1 and 4 hours after injection.

RESULTSNo undesirable effects were reported by the subject during 24 hours after injection of 99Tc(m)N-NOET. No clinically significant changes were found in vital signs (heart rate, blood pressure, and electrocardiogram). No biochemical aspects and serology changes were measured. The myocardial SPECT imaging was clear. Cardiac uptake of 99Tc(m)N-NOET was as high as 2.68% at 2 hours after injection. The heart to lung ratio was more than 1 from 30 minutes after injection, reaching a maximum of 1.91 +/- 0.53 at 2 hours after injection. Radiation dosimetry calculations indicated an effective absorbed dose of 1.28 x 10(-5) Sv/MBq. The dosimetry in each main organ is lower then 50 mGy given 740 MBq of 99Tc(m)N-NOET in once imaging.

CONCLUSIONS99Tc(m)N-NOET exhibits high cardiac uptake and low estimated effective absorbed dose. It's a safe myocardial perfusion imaging agent.

Heart ; diagnostic imaging ; Humans ; Myocardium ; metabolism ; Organotechnetium Compounds ; adverse effects ; pharmacokinetics ; Radiation Dosage ; Radiopharmaceuticals ; adverse effects ; pharmacokinetics ; Thiocarbamates ; adverse effects ; pharmacokinetics ; Tissue Distribution ; Tomography, Emission-Computed, Single-Photon

Soft tissue uptake of Tc-99m labeled bone seeking agents, such as Tc-99m 3,3-diphosphono-1,2-propanedicarboxylic acid (DPD), is commonly seen in clinical practice, even though bone scintigraphy is mainly used to detect bone disease. However, gastric uptake of bone agents in patients with gastric cancer is very rare. And it has been reported that calcified gastric adenocarcinoma appears in only about 5% of all gastric cancer. We report a rare case of bone scintigraphy, single photon emission computed tomography and computed tomography fusion images that demonstrated diffuse gastric uptake of Tc-99m DPD in a patient with advanced gastric cancer.
Stomach Neoplasms/*metabolism ; Stomach/*metabolism ; Radiopharmaceuticals/*pharmacokinetics ; Organotechnetium Compounds/diagnostic use/*pharmacokinetics ; Male ; Humans ; Diphosphonates/diagnostic use/*pharmacokinetics ; Bone and Bones/*radionuclide imaging ; Aged