Clinical correlates of {18F}fluorodopa uptake in five grafted Parkinsonian patients

To assess the efficacy of fetal mesencephalic grafts in Parkinson's disease, it is important to know if the grafted cells survive and are functional. Positron emission tomography (PET) and {18F}fluorodopa ({18F}dopa) have been used to demonstrate the survival of the grafted cells, but the relationship of {18F}dopa uptake changes in the grafted striatum to motor function remains unclear. We investigated this question with 16 serial PET scan in 5 severe parkinsonian patients unilaterally grafted in whom we found a significant and progressive increase of the {18F}dopa uptake in the grafted putamen. The number of patients was too small to assess the sensitivity of {18F}dopa PET scans in individual patients. Yet, by analyzing the 16 serial PET scans we found a correlation between the {18F}dopa uptake (Ki) in the grafted putamen and the percentage of daily time spent “on,” suggesting that Ki changes have a functional meaning. In addition, the Ki values were correlated with the contralateral finger dexterity to the same extent in both the grafted and nongrafted putamen. These results indicate that {18F}dopa uptake reflects the motor function of the opposite side of the body, similarly in the grafted and ungrafted putamen, at least in terms of these tasks. Finally, extrapolating from these correlations offers the suggestion that clinical optimal results of the graft could be achieved if the graft brings the Ki values in the putamen to about two standard deviations of mean control values.

[1]  D. Brooks Functional imaging in relation to parkinsonian syndromes , 1993, Journal of the Neurological Sciences.

[2]  S. Juliano,et al.  Long-term delayed vascularization of human neural transplants to the rat brain , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[3]  Richard S. J. Frackowiak,et al.  Transplantation of fetal dopamine neurons in Parkinson's disease: PET {18F}6‐L‐fluorodopa studies in two patients with putaminal implants , 1992, Annals of neurology.

[4]  Y. Samson,et al.  Peduncular 'Rubral' Tremor and Dopaminergic Denervation , 1995, Neurology.

[5]  Y. Samson,et al.  Bilateral motor improvement and alteration of L-dopa effect in two patients with Parkinson's disease following intrastriatal transplantation of foetal ventral mesencephalon. , 1994, Brain : a journal of neurology.

[6]  G. Antoni,et al.  Striatal kinetics of [11C]‐(+)‐nomifensine and 6‐[18F]fluoro‐L‐dopa in Parkinson's disease measured with positron emission tomography , 1990, Acta neurologica Scandinavica.

[7]  B J Hoffer,et al.  Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson's disease. A detailed account of methodology and a 6-month follow-up. , 1989, Archives of neurology.

[8]  W. Freed Substantia nigra grafts and Parkinson's disease: from animal experiments to human therapeutic trials. , 1991, Restorative neurology and neuroscience.

[9]  J. Perlmutter,et al.  Assessment of fetal tissue transplantation in Parkinson's disease , 1994, Neurology.

[10]  C D Marsden,et al.  The relationship between locomotor disability, autonomic dysfunction, and the integrity of the striatal dopaminergic system in patients with multiple system atrophy, pure autonomic failure, and Parkinson's disease, studied with PET. , 1990, Brain : a journal of neurology.

[11]  H. Kimura,et al.  Human positron emission tomographic [18F]Fluorodopa studies correlate with dopamine cell counts and levels , 1993, Annals of neurology.

[12]  Scott T. Grafton,et al.  Survival of implanted fetal dopamine cells and neurologic improvement 12 to 46 months after transplantation for Parkinson's disease. , 1992, The New England journal of medicine.

[13]  R. Trebossen,et al.  Physical characteristics of the ECAT 953B/31: a new high resolution brain positron tomograph , 1991 .

[14]  Richard S. J. Frackowiak,et al.  Evidence for long‐term survival and function of dopaminergic grafts in progressive Parkinson's disease , 1994, Annals of neurology.

[15]  T Jones,et al.  The nigrostriatal dopaminergic system assessed in vivo by positron emission tomography in healthy volunteer subjects and patients with Parkinson's disease. , 1990, Archives of neurology.

[16]  Isabelle Bloch,et al.  Fast Nonsupervised 3D Registration of PET and MR Images of the Brain , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[17]  A. Björklund,et al.  Intracerebral neural implants: neuronal replacement and reconstruction of damaged circuitries. , 1984, Annual review of neuroscience.

[18]  C. Patlak,et al.  Graphical Evaluation of Blood-to-Brain Transfer Constants from Multiple-Time Uptake Data. Generalizations , 1985, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[19]  Guy V. Sawle,et al.  The role of positron emission tomography in the assessment of human neurotransplantation , 1993, Trends in Neurosciences.

[20]  C. Clough,et al.  Implantation of human fetal ventral mesencephalon to the right caudate nucleus in advanced Parkinson's disease. , 1991, Archives of neurology.

[21]  D. Riemann,et al.  The effects of total sleep deprivation and subsequent treatment with clomipramine on depressive symptoms and sleep electroencephalography in patients with a major depressive disorder * , 1990, Acta psychiatrica Scandinavica.

[22]  D. Calne,et al.  PET Studies of Parkinsonian Patients Treated with Autologous Adrenal Implants , 1989, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[23]  D. Spencer,et al.  Unilateral transplantation of human fetal mesencephalic tissue into the caudate nucleus of patients with Parkinson's disease. , 1992, The New England journal of medicine.

[24]  Anders Björklund Neural transplantation — an experimental tool with clinical possibilities , 1991, Trends in Neurosciences.