CLINICAL ISLET TRANSPLANTATION

F. Saudek, D. Jirak, P. Girman, V. Herynek, M. Desortova, J. Peregrin, Z. Berkova, K. Zacharovova, M. Hajek
, Institute for Clinical and Experimental Medicine, Praha/CZECH REPUBLIC

Body: Introduction. Reliable noninvasive in vivo imaging might help to assess the technical success of islet transplantation and to study the dynamics of the transplanted beta-cell mass. We developed a technique for in vitro islet labeling using a clinically approved MR contrast agent ferucarbotran which makes it possible to detect individual islets as hypoitnense spots on serial MR scans over a period of months in animals. Here we report the first results of a pilot clinical trial which has been initiated in type-1 diabetic islet recipients treated by islet transplantation (ClinicalTrials.gov ID ID: NCT01050166). Metods: Freshly isolated islets (280 - 480 islet equivalents) were cultured in CMRL medium supplemented with ferucarbotran (Resovist, Schering, Gemany) 5μl/ml until transplantation (6 -48 hours). Free iron particles were washed out and the labeled islets were transplanted into the portal vein (9 infusions) in 7 C-peptide negative recipients (5 nonuremic, 2 islet after kidney transplants). The liver area was examined on the next day and 1, 4 and 24 weeks post transplant using a 3T MR scanner with a gradient echo sequence. Hypointense islet spots were counted by manual and computer-assisted calculation. Results: In all recipients, C-peptide levels > 0.5 pmol/ml and near-normal values of HbA1c values were achieved with insulin dose reduction of 50-80%.There was no side effect suspected to be related to the labeling procedure. Following transplantation, hypointense islet spots were detected in all of 7 recipients. Their total number 1 day post transplant was considered as 100%. Typically, a significant decrease was detected at 1 week (on average 60% of the initial value) with subseqent stabilization or only slight decrease for up to 24 weeks. In 2 subjects with labeling period of less than 16 h only few islet spots were detected corresponding to poor islet visualization in phantoms labeled for the same period of time. Conclusion: Clinical islet visualization was safe and successful in in all recipients but was less efficient if labeling period was less than 16 h. Significant decrease of islet spots occurred in the 1st week suggesting early islet destruction or impaired engraftment. Then, the islet spot numbers remained stable for up to 24 weeks. MR detection of ferucarbotran-labeled islets enables their long-term non invasive visualization and correlates with sustained C-peptide production. Longer follow-up in a larger group of recipients will be needed for assessment of its utility for diagnostics of the islet graft status. Acknowledgement: This project is supported by grants No. 2B06175 and LN00A065 MSMT of the Czech Republic

Disclosure: All authors have declared no conflicts of interest.