AIMTo look for new heart or kidney imaging agents. Five new target chelators--2-N-(2'-s-triphenylmethylacetyl) amino-(N'-acetyl glycine) isovalericamide (MVG2), 2-N-(2'-s-triphenylmethylacetyl) amino-[N'-acetyl-(N"-butylacetaminde)] isovalericamide (MVGT), 2-N-(2'-s-tri-phenylmethylacetyl) amino-[N'-acetyl-(N"-cyclohexanylacetaminde)] isovalericamide (MVGH), 2-N-(2'-s-triphenylmethylacetyl) amino-[N'-acetyl-(N"-butylacetaminde)] phenyl propamide (MPGT) and 2-N-(2'-s-triphenylmethylacetyl) amino-[N'-acetyl-(N"-cyclohexanylacetaminde)] phenylpropamide (MPGH) were synthesized as primitive materials to explore the synthetic methods of polypeptides.

METHODS AND RESULTSAll target chelators were identified on the basis of the spectroscopic data, such as IR, 1HNMR, 13CNMR and elementary analysis. Different active esters with mercaptoacetic acid as primitive materials were used to explore the biodistribution of Technetium-99m labelling chelators in mice. The chelators were labeled with Technetium-99m and further tested for the biological activity in mice. Values given in ID which is the percentage injected dose per organ was tested to explore new heart imaging agents. The ID was determined in vivo by biodistribution study. Tc-99m complexes 0.1 mL was injected into laterial tail vein of 3 anaesthetised rats. At 2, 5, 10, 30, 60 minutes post-injection, rats were sacrificed by decapitation, bled from the neck and the organs were removed. The radioactivities in various organs were determined in an automatic twin crystal gamma counter. Five new target chelators were labeled with Technetium-99m in high yield (> 95%). The bio-distribution resulted in mice indicate that 99Tcm-MVG2 has high kidney uptake, good retention, quick blood clearance and high activity ratios of kidneys to other tissues. 99Tcm-MVGT, 99Tcm-MVGH and 99Tcm-MPGT have better heart accumulation, but shorter retention, slower blood clearance and lower activity ratios of kidneys to other tissues. They were mainly metabolized through liver and kidney.

CONCLUSION99Tcm-MVG2 will be a new potential renal function imaging agent and 99Tcm-MVGT, 99Tcm-MVGH and 99Tcm-MPGT will be new potential heart function imaging agents if their structure and activity relationships are further studied.

Animals ; Chelating Agents ; chemical synthesis ; pharmacokinetics ; Kidney ; metabolism ; Mice ; Myocardium ; metabolism ; Organotechnetium Compounds ; chemical synthesis ; pharmacokinetics ; Technetium ; pharmacokinetics ; Tissue Distribution

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

AIMTo explore the synthetic methods of polypeptides containing new heart of kidney imaging agents.

METHODS AND RESULTSFive new target chelators--2-N-(2'-s-triphenylmethylacetyl) amino-(N'-2"-N",N"-diethylethylamine) phenylpropamide (MPNE), 2-N-(2'-s-triphenylmethyl acetyl) amino-(N'-2"-N",N"-dimethylethylamine) phenylpropamide (MPNM), 2-N-(2's-triphenylmethylacetyl) amino-3-methyl-(N'-2"-N",N"-dimethylethylamine) butyramide (MVNM), 2-N-(2'-s-triphenyl methylacetyl) amino-3-methyl-(N'-2"-N",N"-diethylethylamine) butyramide (MVNE), 2-N-(2'-s-triphenylmethylacetyl) amino-(N'-acetylglycine) phenylpropamide (MPG2)--were synthesized through five steps with mercaptoacetic acid as primitive materials, all of which were identified on the basis of spectroscopic data, such as IR, 1HNMR, MS or elementary analysis. The protection of the mercapto group was improved and the relatively new reaction condition of active ester with amino acid is developed. All the chelators were labeled with Technetium-99m and their biological activities in mice given in ID values was tested to explore new heart imaging agents, where ID is the percentage injected dose per organ. The ID was determined by in vivo biodistribution study. Tc-99m complexes 0.1 mL was injected into the laterial tail vein of 3 anaesthetised rats. At 2, 5, 10, 30, 60 min post-injection, rats were sacrificed by decapitation, bled from the neck and dissected. Organs were removed at dissection. The radioactivities in various organs were determined in an automatic twin crystal gamma counter.

CONCLUSIONThe bio-distribution results in mice indicate that 99Tcm-MVNM have higher heart uptake (ID = 8.40%/g, 2 min post-injection) and quicker blood clearance (ID = 4.3%/g, 60 min post-injection); 99Tcm-MPNE and 99Tcm-MPNM also have fairly high heart uptake and quick blood clearance; 99Tcm-MPG2 has better kidney accumulation and higher activity ratios of kidney to blood (about 4).

Amides ; chemical synthesis ; pharmacokinetics ; Animals ; Kidney ; metabolism ; Mice ; Molecular Structure ; Myocardium ; metabolism ; Organotechnetium Compounds ; chemical synthesis ; pharmacokinetics ; Peptides ; chemical synthesis ; chemistry ; pharmacokinetics ; Sulfides ; chemical synthesis ; pharmacokinetics ; Tissue Distribution

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

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

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

OBJECTIVEThe synthesis, biodistribution, and animal imaging of 99mTc- hydrazinonicotinamide-folate (99mTc-HYNIC-Folate) were studied as a folate receptor-targeted tumor imaging agent.

METHODSHYNIC-Folate was synthesized by a muti-step reaction and radiolabeled with 99mTc using tricine and trisodium phenylphosphine-3, 3', 3"-trisulfonate (TPPTS) as coligands. The radiochemical purity and stability of 99mTc HYNIC-Folate was measured. The biodistributions of 99mTc-HYNIC-Folate in normal mice and tumor-bearing mice were detected. Whole-body gamma imaging was performed using an athymic mouse tumor xenograft model.

RESULTSThe ligand HYNIC-Folate was successfully synthesized and characterized by hydrogen nuclear magnetic resonance (1HNMR) and mass spectrometry (MS). The radiochemical purity of 99mTc-HYNIC-Folate was 96% under optimal conditions. Data from gamma scintigraphy and the biodistribution in tumor-bearing mice showed that 99mTc-HYNIC-Folate predominantly accumulated in tumor, its uptake rate per gram tissue alpham was 5. 620+/- 0. 753. The uptakes of 99mTc-HYNIC-Folate in the other non-target tissues were very low, except it was high in the kidneys ( am was 41. 959 +/-6. 759) .

CONCLUSION99mTc-HYNIC-Folate has the potential to be used as a noninvasive radiodiagnostic imaging agent for the detection of folate receptor-positive human cancers.

Animals ; Female ; Mice ; Mice, Inbred BALB C ; Mice, Inbred ICR ; Neoplasms, Experimental ; diagnostic imaging ; Organotechnetium Compounds ; chemical synthesis ; pharmacokinetics ; Radionuclide Imaging ; Radiopharmaceuticals ; chemical synthesis ; pharmacokinetics ; Tissue Distribution

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

We present a patient with Fanconi syndrome who demonstrated poor renal uptake of 99mTc-DMSA and high urinary concentration of the tracer. A 99mTc-DTPA scan was normal and the creatinine clearance only minimally decreased. These findings suggest that 99mTc-DMSA may be accumulated in the kidney by glomerular filtration and subsequent tubular reabsorption, with the nonabsorbed fraction appearing in the urine. In Fanconi Syndrome the tubular reabsorption of DMSA may also be reduced, thus explaining the poor renal uptake in this patient. A 99mTc-MDP bone scan showed faint renal uptake and diffuse high uptake mainly in the spine, demonstrating that the metabolic bone disease associated with Fanconi Syndrome can be another mechanism for poor renal visualization on bone scan.
Fanconi Syndrome/*metabolism/radionuclide imaging ; Female ; Glomerular Filtration Rate ; Humans ; Kidney/*metabolism/radionuclide imaging ; Kidney Glomerulus/*physiology ; Middle Aged ; Organotechnetium Compounds/*pharmacokinetics ; Spine/metabolism/radionuclide imaging ; Succimer/*pharmacokinetics ; Technetium Tc 99m Dimercaptosuccinic Acid ; Technetium Tc 99m Medronate/*pharmacokinetics