Percutaneous image-guided delivery for the transplantation of mesenchymal stem cells in the setting of degenerated intervertebral discs.

PURPOSE: The delivery of mesenchymal stem cells (MSCs) to their site of action has remained a technical hurdle for clinical researchers in the expanding field of stem cell-based therapy. The purpose of this study was to test the feasibility of percutaneous image-guided needle delivery of bone marrow-derived human MSCs (hMSCs) to degenerated intervertebral discs (IVDs) in a preclinical model and to assess the containment of these cells within the IVDs. MATERIALS AND METHODS: Degeneration was induced in the lumbar IVDs of four 28-35-kg female pigs. Approximately 100,000 iodine-124 2'-fluoro-2'-deoxy-1ß-D-arabinofuranosyl-5-iodouracil-labeled hMSCs were delivered under fluoroscopic guidance to one of the affected discs in each of the animals. The remaining levels served as internal controls. The animals were imaged by computed tomography (CT) and positron emission tomography (PET) immediately after delivery and 3 days after the procedure. Fifteen days after transplantation, immunohistochemical staining was performed on harvested discs to confirm the presence of delivered hMSCs. RESULTS: After refinement of the technique, PET-CT images on the day of cell transplantation showed initial deposition of the delivered radiolabeled MSCs to the IVD. An additional PET-CT study obtained 3 days later confirmed persistence and containment of activity in the IVD. Findings of histologic evaluation for the presence of human Alu sequences were positive in the treated discs and negative in the controls. CONCLUSIONS: Image-guided needle delivery of MSCs for treatment of degenerated IVDs is feasible as demonstrated in this preclinical model. Trials of this minimally invasive technique in humans are warranted.

PET imaging of hepatocellular carcinoma with 18F-fluoroethylcholine and 11C-choline.

PURPOSE: Choline-based radiotracers have been studied for PET imaging of hepatocellular carcinoma (HCC). Using an (18)F-labeled choline analog, instead of the (11)C-labeled native choline, would facilitate its widespread use in the clinic. In this study, PET with (18)F-fluoroethylcholine (FEC) and (11)C-choline (CHOL) were compared using an animal model of HCC. The effects of fasting on the performance of choline-based tracers were also investigated. METHODS: A woodchuck model of HCC was used to compare the two tracers, which were administered and imaged in sequence during the same imaging session. Dynamic PET images were generated spanning 50 min starting from tracer injection. Time-activity curves and tracer contrast were calculated in liver regions with tracer accumulation, and the contrast at a late time-point with the two tracers, and between fasted and nonfasted states, were compared. RESULTS: Foci of HCC with increased uptake ranged in size from 1.0 to 1.6 cm, with mean tumor-to-background contrast of 1.3 with FEC and 1.5 with CHOL at 50 min after injection. The tracers show similar patterns of uptake immediately following administration, and both activities plateaued at 10 min after injection. No significant differences in uptake dynamics or final contrast were observed between the fasted and nonfasted states. CONCLUSION: PET imaging of HCC is possible with both CHOL and FEC. Fasting was not found to affect accumulation of either tracer. These results encourage further investigation into the clinical utility of FEC for HCC imaging.

The effect of fasting on PET Imaging of Hepatocellular Carcinoma.

The clinical utility of positron emission tomography (PET) imaging for liver cancer applications is not clearly defined either for diagnosis or treatment assessment. Previous clinical studies demonstrated that fluorodeoxyglucose (FDG) did not show uptake in some hepatocellular carcinoma (HCC) while acetate showed uptake. Pre-imaging fasting is required for clinical PET imaging with FDG. No studies were done to confirm the effect of fasting on acetate uptake in HCC for PET imaging. We investigated this situation with a woodchuck model of viral infection-induced HCC. METHODS: Four tumor-bearing and one control woodchucks were involved in this study. They were first imaged by PET in fed state followed by another imaging session one week later when they were fasted over-night. Some animals also had FDG-PET scan that was acquired later on the same day. After imaging studies, animals were sacrificed, and their liver excised for histology. Standardized Uptake Value (SUV) was calculated using a region of interest (ROI) placed on each tumor with focal uptake. RESULTS: Acetate showed uptake in each HCC lesion when the animals were either fasted or fed with no significant difference in SUV values (p=0.177); some of the tumors were histologically confirmed as well-differentiated HCC while others were confirmed as moderately- or poorly-differentiated HCC; no focal uptake was found in the control animal. For the accompanying FDG scans, the uptake was detected only in animals that were fasted although the uptake pattern was different from that with acetate. CONCLUSION: This study provided a hint that fasting or not has little impact on PET imaging of HCC with acetate. It also confirmed prior finding regarding tumor heterogeneity that led to different tracer uptake pattern in the same tumor. Human studies are needed to validate the findings from this pre-clinical investigation.