Non-random tissue distribution of human na ve umbilical cord matrix stem cells

AIM: To determine the tissue and temporal distribution of human umbilical cord matrix stem (hUCMS) cells in severe combined immunodeficiency (SCID) mice. METHODS: For studying the localization of hUCMS cells, tritiated thymidine-labeled hUCMS cells were injected in SCID mice and tissue distribution was quantitatively determined using a liquid scintillation counter at days 1, 3, 7 and 14. Furthermore, an immunofluorescence detection technique was employed in which anti-human mitochondrial antibody was used to identify hUCMS cells in mouse tissues. In order to visualize the distribution of transplanted hUCMS cells in H&E stained tissue sections, India Black ink 4415 was used to label the hUCMS cells. RESULTS: When tritiated thymidine-labeled hUCMS cells were injected systemically (iv) in female SCID mice, the lung was the major site of accumulation at 24 h after transplantation. With time, the cells migrated to other tissues, and on day three, the spleen, stomach, and small and large intestines were the major accumulation sites. On day seven, a relatively large amount of radioactivity was detected in the adrenal gland, uterus, spleen, lung, and digestive tract. In addition, labeled cells had crossed the blood brain barrier by day 1. CONCLUSION: These results indicate that peripherally injected hUCMS cells distribute quantitatively in a tissue-specific manner throughout the body.

Labeling of Anti-SAS1B with Zirconium-89 as a Novel Immune-PET Probe for Uterine Cancer Imaging

Overexpression of Sperm Acrosomal SLLP1 Binding protein (SAS1B) in various cancer types, including uterine cancer cells, was discovered a few years ago, and different monoclonal antibodies (anti-SAS1B) that specifically bind to SAS1B antigens were developed. Labeling of these antibodies with radionuclides can provide an opportunity for imaging and radioimmunotherapy. The objective of this study was to label anti-SAS1B (SB5) with Zirconium-89 (89Zr) for PET imaging and determine its biodistribution. Anti-SAS1B (SB5) antibody was labeled with 89Zr indirectly using the chelator desferrioxamine B (DFO), which is currently a best linker for 89Zr. The antibody, SB5, was first conjugated to DFO with a ratio of 1:5 and then labeled with 250 μCi of 89Zr. Results of PET imaging in mouse-bearing uterine cancer tumor showed a limited uptake. The bio-distribution study matched the PET imaging and confirmed the uptake by the tumor, and the accumulation in bones. In conclusion, labeling of anti-SAS1B could provide an effective way of uterine cancer detection and treatment progression.

^(99m)Tc-YIGSR as a Receptor Tracer in Imaging the Ehrlich Ascites Tumor-bearing Mice as Compared with ^(99m)Tc-MIBI

The validity of ^99mTc-YIGSR, a novel receptor radio-tracer, in imaging the Ehrlich ascites tumor was evaluated. YIGSR, a pentapeptide of laminin, was labeled with ^99mTc by using a bifunctional chelator S-Acetly-NH3-MAG3. The MIBI was labeled with ^99mTc by following the kit instruction. The mice of tumor group were intravenously injected 1-2 mCi of ^99mTc-YIGSR or ^99mTc-MIBI via caudal vein, immobilized and imaged under a Gamma camera. The same procedure was performed in mice of blockade group, in which the unlabeled YIGSR was previously injected to block the receptor-recognition sites, and inflammation group serving as control. The reverse-phase Sep-Pak C18 chromatogram was found to have an essentially complete conjugation between YIGSR and S-Acetly-NH3-MAG3. The conjugated YIGSR could be radio-labeled successfully with ^99mTC at room temperature and neutral pH, with a radio-labeling yield of 62%. Without the chelator S-Acetly-NH3-MAG3, the YIGSR was labeled with ^99mTc at an efficiency of 4%. The imagological study revealed obvious tumor accumulation of ^99mTc-YIGSR 15 min after the injection, and the uptake peaked after 3 h with a tumor-to-muscle ratio （T/M） of 11.36. The radio-tracer was slowly cleared up and resulted in a T/M of 3.01 at the 8th h after the injection. As for blocked group, the tumor uptake of radiotracer was significantly lower, with the highest T/M being 4.61 after 3 h and 0.89 after 8 h. The T/M was 3.72 at the 3rd h and 1.29 at the 8th h after the ^99mTc-YIGSR injection in the inflammatory group. The T/M was significantly higher in tumor group than in inflammatory group or control group （P〈0.001）. In the ^99mTc-MIBI group, the T/M was 1.40 at the 3rd h and 0.55 at the 8th h after the injection, which showed a significant difference as compared with ^99mTc-YIGSR （P〈0.001）. It is concluded that YIGSR can be successfully radiolabelled by using S-Acetly-NH3-MAG3. ^99mTc-YIGSR has many advantages in tumor imaging, such as quick and clear visualization, high sensitivity and specificity, and satisfactory target/non-target ratio （N/NT）. It promises to be tumor radio-tracer.