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. 2000 May;196(Pt 4):597–607. doi: 10.1046/j.1469-7580.2000.19640597.x

Aspects of PET imaging relevant to the assessment of striatal transplantation in Huntington's disease

LAURENT BESRET 1, A LISA KENDALL 1, STEPHEN B DUNNETT 1,✉
PMCID: PMC1468100  PMID: 10923990

Abstract

Proper assessment of outcome in clinical trials of neural transplantation requires both biochemical and imaging indices of graft survival, and behavioural and physiological indices of graft function. For transplantation in Huntington's disease, a variety of ligands that are selective for striatal degeneration and graft-derived replacement are available, notably ligands of dopaminergic receptors on striatal neurons. However, the validity of such ligands is potentially compromised by adjunctive drug therapies (e.g. neuroleptics) given to patients in the course of normal clinical care. We review the present state of experimental and clinical understanding of the selectivity of available ligands for striatal imaging, their interaction with other drug treatments, and strategies for refining valid assessment protocols in patients.

Keywords: Huntington's disease, striatal transplantation, PET imaging

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Selected References

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  1. Ainsworth K., Smith S. E., Zetterström T. S., Pei Q., Franklin M., Sharp T. Effect of antidepressant drugs on dopamine D1 and D2 receptor expression and dopamine release in the nucleus accumbens of the rat. Psychopharmacology (Berl) 1998 Dec;140(4):470–477. doi: 10.1007/s002130050791. [DOI] [PubMed] [Google Scholar]
  2. Antonini A., Leenders K. L., Eidelberg D. [11C]raclopride-PET studies of the Huntington's disease rate of progression: relevance of the trinucleotide repeat length. Ann Neurol. 1998 Feb;43(2):253–255. doi: 10.1002/ana.410430216. [DOI] [PubMed] [Google Scholar]
  3. Antonini A., Leenders K. L., Spiegel R., Meier D., Vontobel P., Weigell-Weber M., Sanchez-Pernaute R., de Yébenez J. G., Boesiger P., Weindl A. Striatal glucose metabolism and dopamine D2 receptor binding in asymptomatic gene carriers and patients with Huntington's disease. Brain. 1996 Dec;119(Pt 6):2085–2095. doi: 10.1093/brain/119.6.2085. [DOI] [PubMed] [Google Scholar]
  4. Arnt J., Skarsfeldt T. Do novel antipsychotics have similar pharmacological characteristics? A review of the evidence. Neuropsychopharmacology. 1998 Feb;18(2):63–101. doi: 10.1016/S0893-133X(97)00112-7. [DOI] [PubMed] [Google Scholar]
  5. Bachoud-Lévi A. C., Hantraye P., Peschanski M. Prospectives for cell and gene therapy in Huntington's disease. Prog Brain Res. 1998;117:511–524. doi: 10.1016/s0079-6123(08)64036-4. [DOI] [PubMed] [Google Scholar]
  6. Bartenstein P., Weindl A., Spiegel S., Boecker H., Wenzel R., Ceballos-Baumann A. O., Minoshima S., Conrad B. Central motor processing in Huntington's disease. A PET study. Brain. 1997 Sep;120(Pt 9):1553–1567. doi: 10.1093/brain/120.9.1553. [DOI] [PubMed] [Google Scholar]
  7. Brownell A. L., Livni E., Galpern W., Isacson O. In vivo PET imaging in rat of dopamine terminals reveals functional neural transplants. Ann Neurol. 1998 Mar;43(3):387–390. doi: 10.1002/ana.410430318. [DOI] [PubMed] [Google Scholar]
  8. Bäckman L., Robins-Wahlin T. B., Lundin A., Ginovart N., Farde L. Cognitive deficits in Huntington's disease are predicted by dopaminergic PET markers and brain volumes. Brain. 1997 Dec;120(Pt 12):2207–2217. doi: 10.1093/brain/120.12.2207. [DOI] [PubMed] [Google Scholar]
  9. Cross A., Rossor M. Dopamine D-1 and D-2 receptors in Huntington's disease. Eur J Pharmacol. 1983 Mar 25;88(2-3):223–229. doi: 10.1016/0014-2999(83)90009-2. [DOI] [PubMed] [Google Scholar]
  10. Ebert D., Feistel H., Loew T., Pirner A. Dopamine and depression--striatal dopamine D2 receptor SPECT before and after antidepressant therapy. Psychopharmacology (Berl) 1996 Jul;126(1):91–94. doi: 10.1007/BF02246416. [DOI] [PubMed] [Google Scholar]
  11. Farde L., Nordström A. L., Wiesel F. A., Pauli S., Halldin C., Sedvall G. Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects. Arch Gen Psychiatry. 1992 Jul;49(7):538–544. doi: 10.1001/archpsyc.1992.01820070032005. [DOI] [PubMed] [Google Scholar]
  12. Farde L., Wiesel F. A., Stone-Elander S., Halldin C., Nordström A. L., Hall H., Sedvall G. D2 dopamine receptors in neuroleptic-naive schizophrenic patients. A positron emission tomography study with [11C]raclopride. Arch Gen Psychiatry. 1990 Mar;47(3):213–219. doi: 10.1001/archpsyc.1990.01810150013003. [DOI] [PubMed] [Google Scholar]
  13. Filloux F., Wagster M. V., Folstein S., Price D. L., Hedreen J. C., Dawson T. M., Wamsley J. K. Nigral dopamine type-1 receptors are reduced in Huntington's disease: a postmortem autoradiographic study using [3H]SCH 23390 and correlation with [3H]forskolin binding. Exp Neurol. 1990 Nov;110(2):219–227. doi: 10.1016/0014-4886(90)90033-o. [DOI] [PubMed] [Google Scholar]
  14. Florijn W. J., Tarazi F. I., Creese I. Dopamine receptor subtypes: differential regulation after 8 months treatment with antipsychotic drugs. J Pharmacol Exp Ther. 1997 Feb;280(2):561–569. [PubMed] [Google Scholar]
  15. Fricker R. A., Torres E. M., Hume S. P., Myers R., Opacka-Juffrey J., Ashworth S., Brooks D. J., Dunnett S. B. The effects of donor stage on the survival and function of embryonic striatal grafts in the adult rat brain. II. Correlation between positron emission tomography and reaching behaviour. Neuroscience. 1997 Aug;79(3):711–721. doi: 10.1016/s0306-4522(96)00657-4. [DOI] [PubMed] [Google Scholar]
  16. Fricker R. A., Torres E. M., Hume S. P., Myers R., Opacka-Juffrey J., Ashworth S., Brooks D. J., Dunnett S. B. The effects of donor stage on the survival and function of embryonic striatal grafts in the adult rat brain. II. Correlation between positron emission tomography and reaching behaviour. Neuroscience. 1997 Aug;79(3):711–721. doi: 10.1016/s0306-4522(96)00657-4. [DOI] [PubMed] [Google Scholar]
  17. Ginovart N., Lundin A., Farde L., Halldin C., Bäckman L., Swahn C. G., Pauli S., Sedvall G. PET study of the pre- and post-synaptic dopaminergic markers for the neurodegenerative process in Huntington's disease. Brain. 1997 Mar;120(Pt 3):503–514. doi: 10.1093/brain/120.3.503. [DOI] [PubMed] [Google Scholar]
  18. Grafton S. T., Mazziotta J. C., Pahl J. J., St George-Hyslop P., Haines J. L., Gusella J., Hoffman J. M., Baxter L. R., Phelps M. E. Serial changes of cerebral glucose metabolism and caudate size in persons at risk for Huntington's disease. Arch Neurol. 1992 Nov;49(11):1161–1167. doi: 10.1001/archneur.1992.00530350075022. [DOI] [PubMed] [Google Scholar]
  19. Hahn-Barma V., Deweer B., Dürr A., Dodé C., Feingold J., Pillon B., Agid Y., Brice A., Dubois B. Are cognitive changes the first symptoms of Huntington's disease? A study of gene carriers. J Neurol Neurosurg Psychiatry. 1998 Feb;64(2):172–177. doi: 10.1136/jnnp.64.2.172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hayden M. R., Martin W. R., Stoessl A. J., Clark C., Hollenberg S., Adam M. J., Ammann W., Harrop R., Rogers J., Ruth T. Positron emission tomography in the early diagnosis of Huntington's disease. Neurology. 1986 Jul;36(7):888–894. doi: 10.1212/wnl.36.7.888. [DOI] [PubMed] [Google Scholar]
  21. Huang N., Ase A. R., Hébert C., van Gelder N. M., Reader T. A. Effects of chronic neuroleptic treatments on dopamine D1 and D2 receptors: homogenate binding and autoradiographic studies. Neurochem Int. 1997 Mar;30(3):277–290. doi: 10.1016/s0197-0186(96)00093-9. [DOI] [PubMed] [Google Scholar]
  22. Hume S. P., Lammertsma A. A., Myers R., Rajeswaran S., Bloomfield P. M., Ashworth S., Fricker R. A., Torres E. M., Watson I., Jones T. The potential of high-resolution positron emission tomography to monitor striatal dopaminergic function in rat models of disease. J Neurosci Methods. 1996 Aug;67(2):103–112. [PubMed] [Google Scholar]
  23. Hume S. P., Myers R., Bloomfield P. M., Opacka-Juffry J., Cremer J. E., Ahier R. G., Luthra S. K., Brooks D. J., Lammertsma A. A. Quantitation of carbon-11-labeled raclopride in rat striatum using positron emission tomography. Synapse. 1992 Sep;12(1):47–54. doi: 10.1002/syn.890120106. [DOI] [PubMed] [Google Scholar]
  24. Jones T. The imaging science of positron emission tomography. Eur J Nucl Med. 1996 Jul;23(7):807–813. doi: 10.1007/BF00843711. [DOI] [PubMed] [Google Scholar]
  25. Jones T. The role of positron emission tomography within the spectrum of medical imaging. Eur J Nucl Med. 1996 Feb;23(2):207–211. doi: 10.1007/BF01731847. [DOI] [PubMed] [Google Scholar]
  26. Joyce J. N., Lexow N., Bird E., Winokur A. Organization of dopamine D1 and D2 receptors in human striatum: receptor autoradiographic studies in Huntington's disease and schizophrenia. Synapse. 1988;2(5):546–557. doi: 10.1002/syn.890020511. [DOI] [PubMed] [Google Scholar]
  27. Kapur S. A new framework for investigating antipsychotic action in humans: lessons from PET imaging. Mol Psychiatry. 1998 Mar;3(2):135–140. doi: 10.1038/sj.mp.4000327. [DOI] [PubMed] [Google Scholar]
  28. Kendall A. L., Rayment F. D., Torres E. M., Baker H. F., Ridley R. M., Dunnett S. B. Functional integration of striatal allografts in a primate model of Huntington's disease. Nat Med. 1998 Jun;4(6):727–729. doi: 10.1038/nm0698-727. [DOI] [PubMed] [Google Scholar]
  29. Klimek V., Nielsen M. Chronic treatment with antidepressants decreases the number of [3H]SCH 23390 binding sites in the rat striatum and limbic system. Eur J Pharmacol. 1987 Jul 9;139(2):163–169. doi: 10.1016/0014-2999(87)90248-2. [DOI] [PubMed] [Google Scholar]
  30. Kopyov O. V., Jacques S., Lieberman A., Duma C. M., Eagle K. S. Safety of intrastriatal neurotransplantation for Huntington's disease patients. Exp Neurol. 1998 Jan;149(1):97–108. doi: 10.1006/exnr.1997.6685. [DOI] [PubMed] [Google Scholar]
  31. Kuhl D. E., Metter E. J., Riege W. H., Markham C. H. Patterns of cerebral glucose utilization in Parkinson's disease and Huntington's disease. Ann Neurol. 1984;15 (Suppl):S119–S125. doi: 10.1002/ana.410150723. [DOI] [PubMed] [Google Scholar]
  32. Langston J. W., Widner H., Goetz C. G., Brooks D., Fahn S., Freeman T., Watts R. Core assessment program for intracerebral transplantations (CAPIT). Mov Disord. 1992;7(1):2–13. doi: 10.1002/mds.870070103. [DOI] [PubMed] [Google Scholar]
  33. Laruelle M., Jaskiw G. E., Lipska B. K., Kolachana B., Casanova M. F., Kleinman J. E., Weinberger D. R. D1 and D2 receptor modulation in rat striatum and nucleus accumbens after subchronic and chronic haloperidol treatment. Brain Res. 1992 Mar 13;575(1):47–56. doi: 10.1016/0006-8993(92)90421-5. [DOI] [PubMed] [Google Scholar]
  34. Lindvall O., Brundin P., Widner H., Rehncrona S., Gustavii B., Frackowiak R., Leenders K. L., Sawle G., Rothwell J. C., Marsden C. D. Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease. Science. 1990 Feb 2;247(4942):574–577. doi: 10.1126/science.2105529. [DOI] [PubMed] [Google Scholar]
  35. Lindvall O. Neural transplantation: a hope for patients with Parkinson's disease. Neuroreport. 1997 Sep 29;8(14):iii–x. doi: 10.1097/00001756-199709290-00036. [DOI] [PubMed] [Google Scholar]
  36. Lindvall O. Prospects of transplantation in human neurodegenerative diseases. Trends Neurosci. 1991 Aug;14(8):376–384. doi: 10.1016/0166-2236(91)90167-s. [DOI] [PubMed] [Google Scholar]
  37. Madrazo I., Franco-Bourland R. E., Castrejon H., Cuevas C., Ostrosky-Solis F. Fetal striatal homotransplantation for Huntington's disease: first two case reports. Neurol Res. 1995 Aug;17(4):312–315. doi: 10.1080/01616412.1995.11740334. [DOI] [PubMed] [Google Scholar]
  38. Martin W. R., Clark C., Ammann W., Stoessl A. J., Shtybel W., Hayden M. R. Cortical glucose metabolism in Huntington's disease. Neurology. 1992 Jan;42(1):223–229. doi: 10.1212/wnl.42.1.223. [DOI] [PubMed] [Google Scholar]
  39. Nyberg S., Farde L., Halldin C. Delayed normalization of central D2 dopamine receptor availability after discontinuation of haloperidol decanoate. Preliminary findings. Arch Gen Psychiatry. 1997 Oct;54(10):953–958. doi: 10.1001/archpsyc.1997.01830220079011. [DOI] [PubMed] [Google Scholar]
  40. Olanow C. W., Freeman T. B., Kordower J. H. Neural transplantation as a therapy for Parkinson's disease. Adv Neurol. 1997;74:249–269. [PubMed] [Google Scholar]
  41. Olanow C. W., Kordower J. H., Freeman T. B. Fetal nigral transplantation as a therapy for Parkinson's disease. Trends Neurosci. 1996 Mar;19(3):102–109. doi: 10.1016/s0166-2236(96)80038-5. [DOI] [PubMed] [Google Scholar]
  42. Palfi S., Nguyen J. P., Brugieres P., Le Guerinel C., Hantraye P., Remy P., Rostaing S., Defer G. L., Cesaro P., Keravel Y. MRI-stereotactical approach for neural grafting in basal ganglia disorders. Exp Neurol. 1998 Apr;150(2):272–281. doi: 10.1006/exnr.1997.6754. [DOI] [PubMed] [Google Scholar]
  43. Peschanski M., Cesaro P., Hantraye P. Rationale for intrastriatal grafting of striatal neuroblasts in patients with Huntington's disease. Neuroscience. 1995 Sep;68(2):273–285. doi: 10.1016/0306-4522(95)00162-c. [DOI] [PubMed] [Google Scholar]
  44. Philpott L. M., Kopyov O. V., Lee A. J., Jacques S., Duma C. M., Caine S., Yang M., Eagle K. S. Neuropsychological functioning following fetal striatal transplantation in Huntington's chorea: three case presentations. Cell Transplant. 1997 May-Jun;6(3):203–212. doi: 10.1177/096368979700600303. [DOI] [PubMed] [Google Scholar]
  45. Pilowsky L. S., Costa D. C., Ell P. J., Murray R. M., Verhoeff N. P., Kerwin R. W. Clozapine, single photon emission tomography, and the D2 dopamine receptor blockade hypothesis of schizophrenia. Lancet. 1992 Jul 25;340(8813):199–202. doi: 10.1016/0140-6736(92)90467-h. [DOI] [PubMed] [Google Scholar]
  46. Quinn N., Brown R., Craufurd D., Goldman S., Hodges J., Kieburtz K., Lindvall O., MacMillan J., Roos R. Core Assessment Program for Intracerebral Transplantation in Huntington's Disease (CAPIT-HD). Mov Disord. 1996 Mar;11(2):143–150. doi: 10.1002/mds.870110205. [DOI] [PubMed] [Google Scholar]
  47. Richfield E. K., O'Brien C. F., Eskin T., Shoulson I. Heterogeneous dopamine receptor changes in early and late Huntington's disease. Neurosci Lett. 1991 Oct 28;132(1):121–126. doi: 10.1016/0304-3940(91)90448-3. [DOI] [PubMed] [Google Scholar]
  48. Sasaki T., Kennedy J. L., Nobrega J. N. Regional brain changes in [3H]SCH 23390 binding to dopamine D1, receptors after long-term haloperidol treatment: lack of correspondence with the development of vacuous chewing movements. Behav Brain Res. 1998 Feb;90(2):125–132. doi: 10.1016/s0166-4328(97)00092-2. [DOI] [PubMed] [Google Scholar]
  49. Sawle G. V., Myers R. The role of positron emission tomography in the assessment of human neurotransplantation. Trends Neurosci. 1993 May;16(5):172–176. doi: 10.1016/0166-2236(93)90143-a. [DOI] [PubMed] [Google Scholar]
  50. Seeman P., Bzowej N. H., Guan H. C., Bergeron C., Reynolds G. P., Bird E. D., Riederer P., Jellinger K., Tourtellotte W. W. Human brain D1 and D2 dopamine receptors in schizophrenia, Alzheimer's, Parkinson's, and Huntington's diseases. Neuropsychopharmacology. 1987 Dec;1(1):5–15. doi: 10.1016/0893-133x(87)90004-2. [DOI] [PubMed] [Google Scholar]
  51. Shannon K. M., Kordower J. H. Neural transplantation for Huntington's disease: experimental rationale and recommendations for clinical trials. Cell Transplant. 1996 Mar-Apr;5(2):339–352. doi: 10.1177/096368979600500222. [DOI] [PubMed] [Google Scholar]
  52. Sramka M., Rattaj M., Molina H., Vojtassák J., Belan V., Ruzický E. Stereotactic technique and pathophysiological mechanisms of neurotransplantation in Huntington's chorea. Stereotact Funct Neurosurg. 1992;58(1-4):79–83. doi: 10.1159/000098976. [DOI] [PubMed] [Google Scholar]
  53. Tarazi F. I., Florijn W. J., Creese I. Differential regulation of dopamine receptors after chronic typical and atypical antipsychotic drug treatment. Neuroscience. 1997 Jun;78(4):985–996. doi: 10.1016/s0306-4522(96)00631-8. [DOI] [PubMed] [Google Scholar]
  54. Torres E. M., Fricker R. A., Hume S. P., Myers R., Opacka-Juffry J., Ashworth S., Brooks D. J., Dunnett S. B. Assessment of striatal graft viability in the rat in vivo using a small diameter PET scanner. Neuroreport. 1995 Oct 23;6(15):2017–2021. doi: 10.1097/00001756-199510010-00016. [DOI] [PubMed] [Google Scholar]
  55. Turjanski N., Weeks R., Dolan R., Harding A. E., Brooks D. J. Striatal D1 and D2 receptor binding in patients with Huntington's disease and other choreas. A PET study. Brain. 1995 Jun;118(Pt 3):689–696. doi: 10.1093/brain/118.3.689. [DOI] [PubMed] [Google Scholar]
  56. Wenning G. K., Odin P., Morrish P., Rehncrona S., Widner H., Brundin P., Rothwell J. C., Brown R., Gustavii B., Hagell P. Short- and long-term survival and function of unilateral intrastriatal dopaminergic grafts in Parkinson's disease. Ann Neurol. 1997 Jul;42(1):95–107. doi: 10.1002/ana.410420115. [DOI] [PubMed] [Google Scholar]

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