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

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

OBJECTIVETo assess the correlation between uptake of (99)Tc(m)-MIBI and expression level of multidrug resistant protein in breast cancer.

METHODSThirty pathologically confirmed patients with primary invasive ductal carcinoma were examined by (99)Tc(m)-MIBI scintigraphy at 15 min and 90 min after injecting the tracer. The uptake of (99)Tc(m)-MIBI at the region of interest (ROI) was evaluated as tumor to normal background (T/N) ratio. Retention index (RI) was calculated from the early uptake ratio (EUR) and updelayed take ratio (DUR). The expression of P-glycoprotein (P-gp) and multidrug resistant-associated protein (MRP) was detected by immunohistochemistry and the results were expressed as optical density (A). The data were analyzed by t test, Pearson correlation and partial correlation analysis.

RESULTSThe expression of P-gp and MRP in tumor tissue was 0.1183 +/- 0.0700 and 0.1195 +/- 0.0522, respectively. In group with RI < 0. the expression of P-gp and MRP was 0.2181 +/- 0.0384 and 0.1718 +/- 0.0479, respectively. In group with RI >/= 0, the expression of P-gp and MRP was 0.1057 +/- 0.0217 and 0.0967 +/- 0.0362, respectively. There were significant differences between the two groups (t = 6.61, P = 0.0001; t = 5.01, P = 0.002). There was positive correlation between P-gp and RI (r = -0.919, P = 0.001), DUR (r = -0.675, P = 0.001), MRP(r = 0.549, P = 0.001), respectively, but no correlation between P-gp and EUR (r = -0.097, P = 0.610). There was positive correlation between MRP and RI (r = -0.547, P = 0.002), but no correlation between MRP and EUR (r = 0.292, P = 0.117) or DUR (r = -0.173, P = 0.361). Partial correlation analysis showed that there was high positive correlation between P-gp and RI (r = -0.8847, P = 0.001), but no significant correlation between MRP and RI (r = -0.1296, P = 0.512).

CONCLUSIONThe study suggests that increased level of P-gp expression may contribute to a low accumulation of (99)Tc(m)-MIBI in breast cancer, but no correlation with the expression level of MRP. Thus (99)Tc(m)-MIBI scintigraphy may predict the MDR development associated with P-gp expression in breast carcinoma.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Adolescent ; Adult ; Aged ; Breast Neoplasms ; diagnostic imaging ; metabolism ; Carcinoma, Ductal, Breast ; diagnostic imaging ; metabolism ; Female ; Humans ; Middle Aged ; Multidrug Resistance-Associated Proteins ; metabolism ; Radiopharmaceuticals ; pharmacokinetics ; Technetium Tc 99m Sestamibi ; pharmacokinetics ; Tomography, Emission-Computed