KOMENTAR/COMMENTARY
Imaging of Brain Prion Protein Amyloid in Patients with Gertstmann-Sträussler-Scheinker Disease
SLikanJe prionskega proteina možganov beta-amlLoida pri boLnikih z Gerstmann-SträussLer-ScheinkerJevim sindromom
thuy A. tran,1'2 Deniz Kirik1'3
1	Lund University Bioimaging Center, Faculty of Medicine, SE-22184 Lund, Sweden
2	Department of Medical Radiation Physics, Lund University and Lund University Hospital, Lund, Sweden
3	Brain Repair and Imaging in Neural Systems, Department of Experimental Medical Science, Lund University, SE-221 84, Lund, Sweden
Korespondenca/ Correspondence:
Deniz Kirik, PhD, Prof, Brain Repair and Imaging in Neural Systems, Lund University, BMC Dii, SE-221 84 Lund, email: deniz.kirik@med.Lu.se
Ključne besede:
diagnostika, FDDNP, konformaciJske boLezni, PET, sLikanJe možganov
Key words:
brain-imaging, diagnostics, FDDNP, conformationaL diseases, PET
Gerstmann-Straussler- Scheinker (GSS) disease is a transmissible spongiform encephalopathy, which is a rare but fatal ne-urodegenerative disease, characterized by accumulation of an abnormal, protease-re-sistant form of the prion protein (PrP) in the brain.1 Although it typically affects patients from age of 35 to 55, the disease onset could occur in persons as young as 25 years of age.^ While the definitive diagnosis can be made at neuropathological examination of post-mortem tissue, clinical progression is accompanied with changes in the brain that can be followed by either immunoassays for a number of different wet biomarkers or by imaging techniques based on CT and MRI scanning or [18F]-FDG PET.^ However, these imaging methods provide low sensitivity and specificity, indecisive in diagnosing pri-on diseases or giving sensitive readouts of disease progression.
PET imaging using the radiofluorinated 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl) amino]-2-naphthyl}ethylidene)malononi-trile, [18F]-FDDNP has been evaluated in a number of diseases, targeted Amyloid-beta peptide and tangles tau protein in Alzheimer's disease (AD),^'^ depression and anxiety.6
The potential use of FDDNP for detecting the target prion amyloid in GSS [18F]-
-FDDNP had previously been shown to be feasible in at least in vitro tissue specimens.^'® However, its application for in vivo PET imaging had not been investigated in humans. Kepe and coworkers took this approach forward and were the first to demonstrate the feasibility of detecting prion accumulation in living patients with GSS using ([i8F]-FD-DNP PET and published their exciting results recently in Brain Pathology.^
Kepe et al performed [i8F]-FDDNP PET imaging in 6 GSS subjects with known point mutations of the prion protein (PRNP) gene. These data were later compared with [18F] --FDG PET as well as with structural MRI brain scans. The results showed an increased [18F]-FDDNP binding in the cerebellum, neocortex and subcortical areas of all symptomatic gene carriers, which are in agreement with the clinical symptoms while the two asymptomatic gene carriers showed no cortical [i8F]-FDDNP binding. The authors examined further the distribution of [18F]--FDDNP in these patients by comparing it with the in vitro results from brain tissue specimens from deceased GSS subjects. The in vivo accumulation of [i8F]-FDDNP was very closely related to the distribution of prion protein pathology. Another strength in this study is the follow-up examinations in 2 patients after 12-28 months, where the
Citirajte kot/Cite as:
Zdrav Vestn 2011; 80: 969-70
progression of the disease was in agreement with the clinical symptoms. Also, the parallel [i8F]-FDG scans showed reduced glucose metabolism in the neocortex and thalamus, confirming neuronal dysfunction.
It would be desirable to further examine the diagnostic sensitivity and specificity of [18F]-FDDNP for GSS versus AD and other prion-based disorders. The result of these initial studies by Kepe and colleagues are very interesting and have potential for clinical use in the future, providing an additional tool in identifying patients early, at the onset of the disease. Such studies could eventually lead to better tools to quantify the changes in brain amyloid and help to develop better treatments that can promise disease modification.
References
1.	Collins S, McLean CA, Masters CL. Gerstmann--Sträussler-Scheinker syndrome, fatal familial insomnia, and kuru: a review of these less common human transmissible spongiform encephalopathi-es. J Clin Neurosci 2001; 8: 387-97
2.	Synofzik M, Bauer P, Schöls L. Prion mutation D178N with highly variable disease onset and phenotype. J Neurol Neurosurg Psychiatry 2009; 80: 345-346
3.	Small GW, Bookheimer SY, Thompson PM, Cole GM, Huang SC, Kepe V, et al. Current and future uses of neuroimaging for cognitively impaired patients. Lancet Neurol 2008; 7: 161-72
4.	Agdeppa ED, Kepe V, Shoghi-Jadid K, Satya-murthy N, Small GW, Petrič A, et al. In vivo and in vitro labeling ofplaques and tangles in the brain of an Alzheimer's disease patient: a case study. J Nucl Med 2001; 42: 65P.
5.	Shoghi-Jadid K, Small GW, Agdeppa ED, Kepe V, Ercoli LM, Siddarth P, et al. Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. Am J Geriatr Psychiatry 2002; 10: 24-35
6.	Lavretsky H, Siddarth P, Kepe V, Ercoli LM, Miller KJ, Burggren AC, et al. Depression and anxiety symptoms are associated with cerebral FDDNP--PET binding in middle-aged and older nonde-mented adults. Am J Geriatr Phychiatry 2009; 17:
493-502
7.	Bresjanac M, Smid LM, Vovko TD, Petrič A, Barrio JR, Popovic M. Molecular imaging probe 2-(1-{6-[(2-fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)-malononitrile labels prion plaques in vitro. J Neurosci 2003;23: 8029-8033.
8.	Smid LM, Vovko TD, Popovic M, Petrič A, Kepe V, Barrio JR et al. The 2,6-disubstituted naphthalene derivative FDDNP labelingreliably predicts Congo red birefringence of protein deposits in brainsections of selected human neurodegenerative diseases. Brain Pathol 2006;16: 124-130.
9.	Kepe V, Ghetti B, Farlow MR, Bresjanac M, Miller K, Huang SC, et al. PET of brain prion protein amyloid in Gerstmann-Sträussler-Scheinker disease. Brain Pathol 2010; 20: 419-30.