OBJECTIVETo evaluate the in vivo and in vitro stability of (131)I-Herceptin and its form of existence in the blood.

METHODSHerceptin was labelled with iodine-131 using the Iodogen method. (131)I-Herceptin was stored at 4 degrees celsius for 3, 24, 48, 72 and 96 h, and the radiochemical purity (RCP) was measured by high performance liquid chromatography (HPLC). Five rabbits received injections of (131)I-Herceptin and at 1, 3, 6, 24, 48, 72, 96 and 120 h after the injection, blood samples were taken to measure the RCP of (131)I-Herceptin in the serum, and the radio count of the serum and blood cells was calculated.

RESULTSThe baseline RCP of (131)I-Herceptin was (94.9±2.7)%. The RCP was stable after placement at 4 degrees celsius for not over 72 h (F=15.985, P<0.001), but was significantly lowered to (82.6±2.8)% after preservation for over 72 h (t=9.971, P<0.001). Within the time of 1.0 to 96 h after injection in rabbits, (131)I-Herceptin existed mainly in the serum with a radio count of 81%-87%; 24 h after the injection, the RCP of (131)I-Herceptin in the serum was significantly lowered to (75.4±3.9)% (t=6.564, P<0.001).

CONCLUSIONStorage at 4 degrees celsius for no more than 72 h does not obviously affect the activity of (131)I-Herceptin in terms of RCP. After injection in rabbits, (131)I-Herceptin exists mainly in the serum and its radiochemical purity remains stable within 24 h, after which obvious degradation occurs.

Animals ; Antibodies, Monoclonal, Humanized ; pharmacokinetics ; Blood ; metabolism ; Cell Line, Tumor ; Drug Stability ; Humans ; Iodine Radioisotopes ; pharmacokinetics ; Rabbits ; Radiopharmaceuticals ; pharmacokinetics ; Trastuzumab

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

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

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

To investigate a new kind of tumor tracer 99mTc-YIGSR developed from a five amino structure (YIGSR) of the Laminin -chain, which can bind to the laminin receptors of tumor specifically, and radiolabeled with MAG3. (1) Preparation of the 99mTc-YIGSR probe: with S-Acetly-NH3-MAG3 as the chelator and with proper reductants YIGSR was labeled with 99mTc; (2) Cell culture and viability measurement: EAC was maintained in RPMI 1640 supplemented with calf serum; the trypan blue exclusion was applied to calculate the cell viability; (3) Study of the cell dynamic: The EAC's uptake of 99mTc-YIGSR and 99mTc-MIBI was observed at 37 degrees C and 22 degrees C, respectively. (1) The labeling efficiencies of 99mTc-YIGSR and 99mTc-MIBI were (62 +/- 3)% and (96 +/- 2)%, respectively; (2) The cell viability was declined with time of incubation; (3) At 37 degrees C, the EAC'S uptake of 99mTc-YIGSR and 99mTc-MIBI reached the peak of (43.16 +/- 2.4) % and (24.4 +/- 1.8) % at 60 min, respectively; and at 22 degrees C, the highest uptake was (26.5 +/- 2.1) % and (9.47 +/- 1.9) % at 60 min, respectively. The in vitro study suggests that 99mTc-YIGSR is superior to 99mTc-MIBI in cell uptake and has potential value in tumor imaging.
Carcinoma, Ehrlich Tumor/*radionuclide imaging ; Laminin ; Oligopeptides ; Radiopharmaceuticals/diagnostic use ; Radiopharmaceuticals/*pharmacokinetics ; Technetium Tc 99m Mertiatide/diagnostic use ; Technetium Tc 99m Mertiatide/*pharmacokinetics ; Technetium Tc 99m Sestamibi/diagnostic use ; Technetium Tc 99m Sestamibi/*pharmacokinetics ; Tissue Distribution

The purpose of this volunteer study was to investigate whether pretreatment with UDCA before the administration of 99mTc DISIDA affects the biliary excretion of the DISIDA, and whether it can shorten the total imaging time. Ten young, healthy volunteers (eight males, two females, mean age: 26.3 +/- 2.1 years) participated in the study. Hepatobiliary scintigraphies were performed twice per volunteer within three days, for the control and the UDCA-pretreated studies. In the control study, the gallbladder (GB) was observed first in four cases and the intestine was observed first in another four cases; in contrast, in the UDCA challenge study, the GB was observed first in eight cases. The quantitative results for the factors related to the GB differed significantly between the control and challenge studies. When the subjects were pretreated with UDCA, the time duration until visualization of the GB was shortened, and the maximum activity of the GB became more intense. In conclusion, UDCA pretreatment before hepatobiliary scintigraphy can shorten the total imaging time for evaluating functional obstructions of the cystic duct and increase the specificity of the process.
Adult ; Biliary Tract/*radionuclide imaging ; Female ; Humans ; Liver/*radionuclide imaging ; Male ; Radionuclide Imaging/*methods ; Radiopharmaceuticals/*pharmacokinetics ; Technetium Tc 99m Disofenin/*pharmacokinetics ; Ursodeoxycholic Acid/*pharmacology

OBJECTIVETo assess the relationship between histological type and fluorine-18 fluorodeoxyglucose(FDG) uptake in patients with primary lung cancer and the factors affecting FDG uptake.

METHODSFrom October 1998 to April 2001, 82 patients with lung cancer were imaged with FDG-PET (Positron emission tomography) before surgery or biopsy. Their maximum and mean standard uptake value(SUVmax and SUVmean) of tumor and SUV of normal lung (SUVlung) were measured.

RESULTSAll tumors were detected by FDG-PET(r)FDG uptake of tumor was higher than that of normal lung (P < 0.01). FDG uptake was lower in adenocarcinoma(AC) than in squamous cell carcinoma (SQC), and that of bronchial aveolar carcinomas(BAC) was the lowest [SUVmax was 8.42 +/- 4.05,5.91 +/- 3.91 and 2.97 +/- 1.10, respectively; SUVmean was 6.12 +/- 2.90,4.35+/- 3.10 and 2.25 +/- 0.99, respectively (P < 0.01)]. Correlations were found between FDG uptake and tumor size (P < 0.01)(r)Glucose level and SUV of normal lung could affect SUV of lung cancer (P < 0.05).

CONCLUSIONSSUV is higher in cancer tissue than in normal lung tissue. FDG uptake is different among SQC,AC and BAC. FDG uptake and tumor size appear to be correlated with each other.SQC, AC and BAC have their own features respectively. The effects of glucose and SUV lung should be considered in the diagnosis of lung cancer with PET.

Adult ; Aged ; Aged, 80 and over ; Blood Glucose ; analysis ; Female ; Fluorodeoxyglucose F18 ; pharmacokinetics ; Humans ; Lung Neoplasms ; diagnostic imaging ; metabolism ; Male ; Middle Aged ; Radiopharmaceuticals ; pharmacokinetics ; Tomography, Emission-Computed

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

BACKGROUNDThe YIGSR is a pentapeptide, from the laminin-1 of the beta1 chain, which can mediate cell adhesion and bind the 67 kD laminin receptor. The purpose is to evaluate the usefulness of (99m)Tc-YIGSR, a novel tumour radiotracer, in the receptor imaging of Ehrlich ascites tumour.

METHODSUsing S-acetly-NH3-MAG3 as chelate, YIGSR, a pentapeptide from laminin, was tagged with (99m)Tc. (99m)Tc-YIGSR was detected in the tumour group bearing Ehrlich ascites tumour and blocked group. Tumour, normal, inflammatory and blocked groups were imaged.

RESULTSThrough reverse phase Sep-Pak C18 chromatogram, it was revealed that YIGSR could conjugate with S-acetly-NH3-MAG3, and be radiolabelled at room temperature and neutral pH with a radiolabelling yield of 62%, and of 4% without chelate. (99m)Tc-YIGSR was rapidly cleared from kidney, then liver. The imaging findings showed tumour tissue accumulated initial radioactivity at fifteen minutes after injection in the tumour group, and the uptake increased to peak at three hours with a tumour/muscle ratio (T/M) of 11.36, then cleared slowly to a T/M of 7.50 at eight hours. The tumour uptake of radiotracer in blocked group was significantly lower with T/M of 4.61 at three hours and 0.89 at eight hours. The T/M was only 3.72 at three hours and 1.29 at eight hours after injection in inflammatory group. Compared with inflammatory group and control obstructive group, the ratio of T/M in tumour group was significantly different (P < 0.001).

CONCLUSIONSUsing S-acetly-NH3-MAG3, we radiolabelled YIGSR with (99m)Tc. (99m)Tc-YIGSR possesses many merits of tumour imaging: rapid visualization, high sensitivity and specificity, and satisfactory target/nontarget ratio. Our data suggest (99m)Tc-YIGSR is a promising tumour radiotracer.

Animals ; Carcinoma, Ehrlich Tumor ; diagnostic imaging ; Female ; Laminin ; Mice ; Oligopeptides ; pharmacokinetics ; Radionuclide Imaging ; Radiopharmaceuticals ; pharmacokinetics ; Technetium ; Technetium Tc 99m Mertiatide ; Tissue Distribution