Monitoring of Bone Marrow Cell Homing in the Infarcted Human Myocardium by PET.

Intracoronary transfer of autologous bone marrow cells (BMCs) has been shown to promote recovery of left ventricular (LV) systolic function in patients with acute myocardial infarction. (BOOST Trial; Wollert et al. Lancet, 2004, 364 141-8). Although the mechanisms of this effect remain to be established, homing of BMCs to the infarcted LV is probably a crucial early event. We determined BMC tissue distribution after therapeutic application in nine patients with a first ST-elevation myocardial infarction, who had undergone stenting of the infarct-related artery (all male; median age 43 ys; range 36 – 66). The study was approved by the local ethics committee and all patients provided written informed consent. Time from symptom onset to percutaneous coronary intervention (PCI) was 8 h (3–27) and median maximum CK level was 1767 U/l. Cells were harvested from the posterior iliac crest during short anesthesia with etomidate and midazolam and subjected to 4% gelatine polysuccinate sedimentation to obtain a preparation of unfractionated BMCs. 2.5 ± 0,7 x 10⁸ unfractionated BMCs (10% of the harvested cell number) were radiolabeled with 100 MBq 2′-[¹⁸F]-fluoro-deoxyglucose (FDG) and infused into the infarct-related coronary artery (i.c., n=3 patients) or injected via an antecubital vein (i.v., n=3 patients). In 3 additional patients, CD34^pos cells were immunomagnetically enriched from unfractionated BMCs (Clinimacs, Miltenyi, Germany), labeled with FDG, and infused i.c. Cell transfer was performed 8±2 days after stenting. Following application of FDG labelled cells all patients received 20 ± 6 x 10⁸ non-labeled BMCs i.c. (i.e. the cell dosage that improved cell function in the BOOST trial). More than 98% of the total radioactivity infused was cell-bound. Cell viability after FDG-labeling was 95±2%. Sixty minutes after cell transfer, all patients underwent 3D-positron emission tomography imaging. After i.c. transfer, 3.4±1.4% of FDG-labeled unfractionated BMCs were detected in the infarcted LV; the remaining activity was found primarily in the liver and spleen. After i.v. transfer, only background activity was detectable in the infarcted LV. After i.c. transfer of FDG-labeled CD34-enriched cells, 25±13% of the total activity was detectable in the infarcted LV. Unfractionated BMCs engrafted in the infarct center and border zone, CD34^pos cell homing was more pronounced in the border zone. FDG-labeling can be used to monitor myocardial homing and tissue distribution of BMCs after therapeutic application. I.c. transfer is superior to i.v. application in terms of BMC homing in the the infarcted LV. CD34-enriched cells display a 7-fold higher retention in the infarcted LV as compared to unfractionated BMCs.