Long-term assessment of striatal dopamine transporters in parkinsonian patients with intrastriatal embryonic mesencephalic grafts

Purpose: Single-photon emission computed tomography (SPECT) of striatal dopamine transporters (DAT) has been used to demonstrate presynaptic dopaminergic dysfunction and to monitor the progression of Parkinson's disease. In parkinsonian patients who were implanted with embryonic mesencephalic tissue in the striatum, positron emission tomography (PET) has shown an increase in striatal [F-18]dopa uptake as an indicator of graft survival and striatal reinnervation. The aim of this study was to investigate two patients who had undergone bilateral intrastriatal transplantation of human embryonic mesencephalic tissue using SPECT and the I-123-labelled DAT ligand N-(3-iodopropen-2-yl)-2 beta-carbomethoxy-3 beta-(4-chlorophenyl) tropane (IPT). Methods: Two patients were subjected to [I-123]IPT SPECT according to a standardised protocol prospectively and repeatedly up to 8 years after transplantation. Results: From baseline to year 3 after transplantation, mean striatal DAT availability increased by a mean of 61% (93% and 29% in patients 1 and 2, respectively). It then remained relatively stable up to 8 years in patient 2, but increased further by another 77% of baseline values in patient 1. Clinically, both patients experienced a moderate improvement in motor performance but developed moderate (patient 2) to severe (patient 1) off-medication dyskinesias. Conclusion: Our data indicate that DAT imaging using IPT and SPECT can be used to demonstrate graft survival following dopaminergic tissue implantation. Because SPECT with DAT ligands is widely available in the routine clinical setting, this methodology may be a useful alternative to [F-18]dopa PET for repeated scanning of grafted parkinsonian patients. The relevance of the long-term increase in DAT binding for the development of off-medication dyskinesias remains to be elucidated further.