Work

Longitudinal multimodal monitoring of transplanted islet β-cells

Year: 2024

Type: article

Abstract: Monitoring β-cell mass and function would provide a better understanding of diabetes, setting the stage for truly individualized therapies. We applied a combined PET/MRI protocol to monitor engrafted islets mass and function without pre-labeling of isolated cells. A PET tracer binding to GLP-1R quantifies β-cell mass, while Mn-CA characterizes β-cell function. Both parameters were assessed in transplanted and native β-cells in vivo and validated with autoradiography and mass spectrometry imaging. Islets were collected and transplanted into the calves of C3H-mice. Accumulation of [ 64 Cu]Ex4 and Mn-CA was examined with a PET/MRI at 1 h post-injection between 1 and 4 weeks after the transplantation. A separate blocking study with diazoxide targeted the functionality of the transplanted islets. As validation, ex vivo autoradiography and LA-ICP-MS imaging were performed after the last imaging session. PET/MRI monitored the engraftment of transplanted islets and visualized an increasing uptake of the PET tracer and Mn-CA . The Mn-CA accumulated at a higher islet-to-background ratio in the calf of mice than in the pancreas due to the high retention of Mn-CA in the exocrine pancreas. In vivo imaging data correlated well with autoradiography and LA-ICP-MS imaging, validating the in vivo approaches. For the quantification of β-cell function, Mn-based contrast mechanisms between native and transplanted islets differ and require further studies for optimal biological readout. However, non-invasive PET/MRI nonetheless provides the tools to investigate the relationship between β-cell mass and function in pancreatic islets. • Combined PET/MRI quantifies mass and function of pancreatic and transplanted β-cell islets • Mn-CA is actively internalized in the intracellular space of islets • Ex vivo LA-ICP-MS imaging of 44 Ca and 64 Zn and autoradiography of [ 64 Cu]Ex4 validated in vivo findings

Source: Nuclear Medicine and Biology

DOI: 10.1016/j.nucmedbio.2024.108962