RADIOPHARMACEUTICALS FOR NEUROIMAGING. Prof. Cristina Maria Moriguchi Jeckel Brain Institute of Rio Grande do Sul, PUCRS
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1 RADIOPHARMACEUTICALS FOR NEUROIMAGING Prof. Cristina Maria Moriguchi Jeckel Brain Institute of Rio Grande do Sul, PUCRS Workshop on Quantitative SPECT and PET Brain Studies BRA6024 PUCRS, Porto Alegre, January 14th 16th, 2013
2 Summary Cerebral Blood Flow and Metabolism o Cerebral Oxygen Metabolism o Cerebral Glucose Metabolism Neuroreceptors and transporters o Dopamine System o Serotonin System o Cholinergic System o Opiate System o GABA System Neurodegenerative processes o Alzheimer s disease o Parkinson s disease Neuroinflammatory processes Neurooncologic processes
3 Ideal characteristics for any radiopharmaceutical Rapid plasma clearance Low nonspecific binding No peripheral metabolism High membrane permeability and intracellular trapping Specificity and high affinity for molecular targets Specific activity must be high to prevent sites saturation Tissue distribution and target binding should be favorable for developing kinetic modeling to estimate quantitative data Radiation dosimetry favorable for multiple imaging studies Rapid and suitable synthesis
4 Criteria for adequate brain penetration Lipophilicity (Log P or Log D = ) Molecular weight < 450 g/mol Metabolically stable (an absence of functional groups that will strongly ionize at physiological ph) No affinity for efflux pumps (such as PGP) Not a substrate for enzymes at the BBB
5 Cerebral blood flow SPECT 99m Tc-HMPAO (Ceretec ) 99m Tc-ECD (Neurolite ) [ 15 O]H 2 O PET Karadag F et al.(2012) Psychiatry Research: Neuroimaging. Baron & Jones NeuroImage 61 (2012)
![Cerebral glucose metabolism PET [ 18 F]FDG Reiman,](/docs-images/80/82014335/images/6-1.jpg "EM & Jagust, WJ, 2012 Neuroimage 61 (2012) 505-516")
6 Cerebral glucose metabolism PET [ 18 F]FDG Reiman, EM & Jagust, WJ, 2012 Neuroimage 61 (2012)
7 Cerebral glucose metabolism in neurooncology [ 18 F]FDG SUV 5 [ 11 C]MET 0 Ishiwata K. et al, 2012
8 Imaging Alcohol s Effects on the Human Brain Glucose is the major energy source in the brain. 18 FDG, a labeled form of glucose, detects profound reductions of brain function with alcohol intoxication.
9 Brain receptors and transporters nutritionwonderland.com (2009)
10 Dopamine System Cumming JL et al. Brain 2011: 134;
11 Dopamine system integral-options.blogspot.com
12 Dopamine system MAO A MAO B integral-options.blogspot.com
13 Dopamine System O Cl N 11 CH3 11 C-Clorg MAO A DA 11 CH 3 N 11 C-Coc CO 2 CH 3 OCOC 6 H 5 Cl MAO A MAO B DA DA DA DA transporters DA H MAO B * N 11 H 3 C 11 C-Dep CH 3 D D signal HO Cl CONHCH 2 O 11 CH 3 Cl N C 2 H 5 11 C-Raclopride DA receptors 18 F-FDG OH H O HO HO 18 F OH
14 Serotonin System PET 5-HT 1A receptor: 11 C-DWAY; 18 F-MPPF 5-HT 2A receptor: 18 F-Altanserin; 18 F-Setoperone 5-HT transporter: 11 C-DASP SPECT 123 I-IDAM/ 123 I-ADAM Holmes, A. Neuroscience and Biobehavioral Reviews 32 (2008)
15 Cholinergic System PET mach receptor: 18 F- FP-TZTP nach receptor: 18 F- NFEP Acetilcolinesterase: 11 C- AMP and PMP SPECT 123 I- QNB
16 Opiate system integral-options.blogspot.com
17 Opiate system (Dannals 1985; Jewett 2001; Studenov 2003) µ opiate receptor agonist basal ganglia and thalamus (Channing 1985) µ and κ opiate antagonist caudate, amygdala, thalamus and brain stem (Luthra 1985,1994; Lewer 1987) Nonselective opioid agonist (Ravert 1999) κ opiate antagonist - 11 C GR (its stereotactic isomer displays excellent brain penetration and uptake kinetics (Talbot et al., 2005) (Luthra 1985,1997; Lewer 1990) Both agonist and antagonist properties
![GABA System Summation images of [ 11 C]flumazenil (A) and [ 18 F]flumazenil (B) of a pacient from 0 to 93 min after i.v. injection.](/docs-images/80/82014335/images/18-1.jpg "Coronal, sagital, horizontal and T1-weighted MR images are shown. Note no uptake of both radioligands in the skull, which is evident by visual inspection of PET and MR images.")
18 GABA System Summation images of [ 11 C]flumazenil (A) and [ 18 F]flumazenil (B) of a pacient from 0 to 93 min after i.v. injection. Coronal, sagital, horizontal and T1-weighted MR images are shown. Note no uptake of both radioligands in the skull, which is evident by visual inspection of PET and MR images. Odano I et al. NeuroImage 45 (2009)
19 GABA System A 39-year-old woman with daily intractable focal motor seizures localizing to the right arm. Ictal SPECT 123 I iomazenil - revealed focal hyperperfusion correlating to left posterior cortical dysplasia on fluid attenuation inversion recovery MRI. Subsequent magnetoencephalography localized a seizure focus to the same region. Horky & Treves, Neurosurg Clin N Am 22 (2011)
![Β-Amyloid Imaging MRI [ 18 F]FDG [ 11](/docs-images/80/82014335/images/20-1.jpg "C]PIB [ 11 C]BF-227 Ishiwata K.")
20 Β-Amyloid Imaging MRI [ 18 F]FDG [ 11 C]PIB [ 11 C]BF-227 Ishiwata K. et al, 2012
21 Comparison of 11 C-PIB, 11 C-BF-227, 18 F-FDG and Gray matter alterations in the same AD patients (n=5) Amyloid burden Amyloid burden Hypometabolism Gray matter loss PIB Increase P>0.001 BF-227 Increase P>0.01 FDG Decrease P>0.001 Gray Decrease P> Ishiwata K. et al., 2012
22 Neuroinflammatory processes PET SPECT 18 F- FDG (high background) 123 I- ZM C- PK11195 (high level of non-specific binding) 11 C- Ro C- DAA1106; 11 C- PBR28; 18 F- DPA C- CFT + 11 C- PK to examine the viability of the presynaptic dopaminergic neurons (Ouchi et al., 2009).
![Neurooncologic processes [ 11 C]MET [ 18 F]FBPA [ 11 C]MET [](/docs-images/80/82014335/images/23-1.jpg "18 F]FBPA Case 1 Case 3 Case 2 Case 4 Ishiwata K.")
23 Neurooncologic processes [ 11 C]MET [ 18 F]FBPA [ 11 C]MET [ 18 F]FBPA Case 1 Case 3 Case 2 Case 4 Ishiwata K. et al, 2012
24 Neurooncologic processes MRI, T1 post-contrast Early phase, FDG-PET (60 min) Late phase, FDG-PET (6.5 hrs) Horky & Treves, Neurosurg Clin N Am 22 (2011)
25 Neurooncologic processes Horky & Treves, Neurosurg Clin N Am 22 (2011)
26 Thank you for your attention Cristina Maria Moriguchi Jeckel
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