ABSTRACT
This pilot trial aimed to investigate the utilization of (111)In-labeling of mesenchymal stromal cells (MSC) for in vivo tracking after intramyocardial transplantation in a xenotransplantation model with gender mismatched cells. Human male MSC were expanded ex vivo and labeled with (111)In-tropolone. Ten female pigs were included. The labeled cells were transplanted intramyocardially using a percutaneous injection system. The (111)In activity was determined using gamma camera imaging. Excised hearts were analyzed by fluorescence in situ hybridization (FISH) and microscopy. Gamma camera imaging revealed focal cardiac (111)In accumulations up to 6 days after injection (N = 4). No MSC could be identified with FISH, and microscopy identified widespread acute inflammation. Focal (111)In accumulation, inflammation but no human MSC were similarly seen in pigs (N = 2) after immunosuppression. A comparable retention of (111)In activity was observed after intramyocardial injection of (111)In-tropolone (without cells) (N = 2), but without sign of myocardial inflammation. Injection of labeled non-viable cells (N = 1) also led to high focal (111)In activity up to 6 days after intramyocardial injection. As a positive control of the FISH method, we identified labeled cells both in culture and immediately after cell injection in one pig. This pilot trial suggests that after intramyocardial injection (111)In stays in the myocardium despite possible disappearance of labeled cells. This questions the clinical use of (111)In-labeled cells for tracking. The results further suggest that xenografting of human MSC into porcine hearts leads to inflammation contradicting previous studies implying a special immunoprivileged status for MSC.
Subject(s)
Heart/diagnostic imaging , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/diagnostic imaging , Myocardium/pathology , Organometallic Compounds , Radiopharmaceuticals , Staining and Labeling/methods , Tropolone/analogs & derivatives , Animals , Cell Death , Cells, Cultured , Chromosomes, Human, Y , Female , Humans , In Situ Hybridization, Fluorescence , Inflammation/diagnostic imaging , Inflammation/pathology , Injections, Intramuscular , Male , Mesenchymal Stem Cells/pathology , Pilot Projects , Radionuclide Imaging , Swine , Time Factors , Transplantation, Heterologous , X ChromosomeABSTRACT
Artefacts hamper the accuracy of myocardial single-photon emission tomography (SPET). Systems are now available that may compensate for attenuation and scatter. We evaluated a commercial system for attenuation (AC) and scatter correction (SC) in everyday routine using coronary angiography (CAG) as a reference. A total of 142 consecutive patients referred for myocardial SPET had their studies processed with and without SCAC. Uncorrected and SCAC images were scored by blinded, consensus readings. If readings differed, CAG, if available, was used as a reference. The readings differed in 37% of cases. Among these cases SCAC caused disappearance of irreversible defects (74%), disappearance of reversible defects (14%) and change of irreversible to reversible defects (9%). Two new defects were introduced by SCAC. The defects influenced were located inferiorly (75%), anteriorly (14%), septally (7%), laterally (2%) and apically (2%). CAG, available in 29 of the discrepant cases, supported SCAC and uncorrected image readings in 83% and 7% of cases, respectively. In conclusion, we found a commercial system for AC and SC in myocardial SPET to be of great diagnostic help in a consecutive series of patients. Using CAG as a reference, the SCAC interpretation was confirmed in nearly all cases.
