Comparing Amyloid-β Deposition, Neuroinflammation, Glucose Metabolism, and Mitochondrial Complex I Activity in Brain: a PET Study in Aged Monkeys

Overview

Journal Eur J Nucl Med Mol Imaging

Specialties Biophysics
Nuclear Medicine
Radiology

Date 2014 Jun 13

PMID 24919653

Citations 23

Authors

Hideo Tsukada

Shingo Nishiyama

Hiroyuki Ohba

Masakatsu Kanazawa

Takeharu Kakiuchi

Norihiro Harada

Affiliations

Soon will be listed here.

Abstract

Purpose: The aim of the present study was to compare amyloid-β (Aβ) deposition, translocator protein (TSPO) activity, regional cerebral metabolic rate of glucose (rCMRglc), and mitochondrial complex I (MC-I) activity in the brain of aged monkeys.

Methods: PET scans with (11)C-PIB (Aβ), (18)F-BCPP-EF (MC-I), (11)C-DPA-713 (TSPO), and (18)F-FDG (rCMRglc) were performed in aged monkeys (Macaca mulatta) in the conscious state and under isoflurane anaesthesia. (11)C-PIB binding to Aβ and (11)C-DPA-713 binding to TSPO were evaluated in terms of standard uptake values (SUV). The total volume of distribution (V T) of (18)F-BCPP-EF and rCMRglc with (18)F-FDG were calculated using arterial blood sampling.

Results: Isoflurane did not affect MC-I activity measured in terms of (18)F-BCPP-EF uptake in living brain. There was a significant negative correlation between (18)F-BCPP-EF binding (V T) and (11)C-PIB uptake (SUVR), and there was a significant positive correlation between (11)C-DPA-713 uptake (SUV) and (11)C-PIB uptake. In contrast, there was no significant correlation between rCMRglc ratio and (11)C-PIB uptake.

Conclusion: (18)F-BCPP-EF could be a potential PET probe for quantitative imaging of impaired MC-I activity that is correlated with Aβ deposition in the living brain.

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References

Lenaz G, Cavazzoni M, Genova M, DAurelio M, Merlo Pich M, Pallotti F . Oxidative stress, antioxidant defences and aging. Biofactors. 1999; 8(3-4):195-204. DOI: 10.1002/biof.5520080305. View

Nicholls D, Budd S . Mitochondria and neuronal survival. Physiol Rev. 2000; 80(1):315-60. DOI: 10.1152/physrev.2000.80.1.315. View

Robinson B . Human complex I deficiency: clinical spectrum and involvement of oxygen free radicals in the pathogenicity of the defect. Biochim Biophys Acta. 1998; 1364(2):271-86. DOI: 10.1016/s0005-2728(98)00033-4. View

Sokoloff L, Reivich M, Kennedy C, Des Rosiers M, PATLAK C, Pettigrew K . The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem. 1977; 28(5):897-916. DOI: 10.1111/j.1471-4159.1977.tb10649.x. View

Reivich M, Alavi A, Wolf A, Fowler J, Russell J, Arnett C . Glucose metabolic rate kinetic model parameter determination in humans: the lumped constants and rate constants for [18F]fluorodeoxyglucose and [11C]deoxyglucose. J Cereb Blood Flow Metab. 1985; 5(2):179-92. DOI: 10.1038/jcbfm.1985.24. View

Hanley P, Ray J, Brandt U, Daut J . Halothane, isoflurane and sevoflurane inhibit NADH:ubiquinone oxidoreductase (complex I) of cardiac mitochondria. J Physiol. 2002; 544(3):687-93. PMC: 2290615. DOI: 10.1113/jphysiol.2002.025015. View

Oberdorfer F, Hull W, Traving B, MAIER-BORST W . Synthesis and purification of 2-deoxy-2-[18F]fluoro-D-glucose and 2-deoxy-2-[18F]fluoro-D-mannose: characterization of products by 1H- and 19F-NMR spectroscopy. Int J Rad Appl Instrum A. 1986; 37(8):695-701. DOI: 10.1016/0883-2889(86)90263-7. View

Kannurpatti S, Sanganahalli B, Mishra S, Joshi P, Joshi N . Glutamate-induced differential mitochondrial response in young and adult rats. Neurochem Int. 2003; 44(5):361-9. DOI: 10.1016/s0197-0186(03)00164-5. View

Klunk W, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt D . Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Ann Neurol. 2004; 55(3):306-19. DOI: 10.1002/ana.20009. View

10.

Tsukada H, Nishiyama S, Fukumoto D, Kanazawa M, Harada N . Novel PET probes 18F-BCPP-EF and 18F-BCPP-BF for mitochondrial complex I: a PET study in comparison with 18F-BMS-747158-02 in rat brain. J Nucl Med. 2014; 55(3):473-80. DOI: 10.2967/jnumed.113.125328. View

11.

Harada N, Nishiyama S, Kanazawa M, Tsukada H . Development of novel PET probes, [18F]BCPP-EF, [18F]BCPP-BF, and [11C]BCPP-EM for mitochondrial complex 1 imaging in the living brain. J Labelled Comp Radiopharm. 2013; 56(11):553-61. DOI: 10.1002/jlcr.3056. View

12.

Boutin H, Chauveau F, Thominiaux C, Gregoire M, James M, Trebossen R . 11C-DPA-713: a novel peripheral benzodiazepine receptor PET ligand for in vivo imaging of neuroinflammation. J Nucl Med. 2007; 48(4):573-81. DOI: 10.2967/jnumed.106.036764. View

13.

Baek B, Kwon H, Lee K, Yoo M, Kim K, Ikeno Y . Regional difference of ROS generation, lipid peroxidation, and antioxidant enzyme activity in rat brain and their dietary modulation. Arch Pharm Res. 1999; 22(4):361-6. DOI: 10.1007/BF02979058. View

14.

Logan J, Volkow N, Fowler J, Wang G, Dewey S, MacGregor R . Effects of blood flow on [11C]raclopride binding in the brain: model simulations and kinetic analysis of PET data. J Cereb Blood Flow Metab. 1994; 14(6):995-1010. DOI: 10.1038/jcbfm.1994.132. View

15.

Finch C, Austad S . Primate aging in the mammalian scheme: the puzzle of extreme variation in brain aging. Age (Dordr). 2012; 34(5):1075-91. PMC: 3448989. DOI: 10.1007/s11357-011-9355-9. View

16.

Tsukada H, Ohba H, Nishiyama S, Kanazawa M, Kakiuchi T, Harada N . PET imaging of ischemia-induced impairment of mitochondrial complex I function in monkey brain. J Cereb Blood Flow Metab. 2014; 34(4):708-14. PMC: 3982099. DOI: 10.1038/jcbfm.2014.5. View

17.

Hardy J, Selkoe D . The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science. 2002; 297(5580):353-6. DOI: 10.1126/science.1072994. View

18.

Choi B . Oxidative stress and Alzheimer's disease. Neurobiol Aging. 1995; 16(4):675-8. DOI: 10.1016/0197-4580(95)00065-m. View

19.

Tsukada H, Ohba H, Kanazawa M, Kakiuchi T, Harada N . Evaluation of 18F-BCPP-EF for mitochondrial complex 1 imaging in the brain of conscious monkeys using PET. Eur J Nucl Med Mol Imaging. 2013; 41(4):755-63. DOI: 10.1007/s00259-013-2628-z. View

20.

Monson N, Ireland S, Ligocki A, Chen D, Rounds W, Li M . Elevated CNS inflammation in patients with preclinical Alzheimer's disease. J Cereb Blood Flow Metab. 2013; 34(1):30-3. PMC: 3887357. DOI: 10.1038/jcbfm.2013.183. View