P Finley

Johns Hopkins Medicine, Baltimore, MD, United States

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Publications (23)71.87 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The radiosynthesis and in vivo evaluation of 5-(5-(6-[(11)C]methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin-2-yl)-1H-indole [(11)C]rac-(1), a potential PET tracer for α7 nicotinic acetylcholine receptors (α7-nAChR), are described. Syntheses of the nonradioactive standard rac-1 and corresponding desmethyl precursor 7 were achieved in several reaction steps. Radiomethylation of 7 with [(11)C]CH(3)I afforded [(11)C]rac-1 in an average radiochemical yield of 30 ± 5% (n=5) with high radiochemical purity and an average specific radioactivity of 444 ± 74 GBq/μmol (n=5). The total synthesis time was 30 min from end-of-bombardment. Biodistribution studies in mice showed that [(11)C]rac-1 penetrates the blood-brain barrier and specifically labels neuronal α7-nAChRs.
    Bioorganic & medicinal chemistry 05/2012; 20(12):3698-702. · 2.82 Impact Factor
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    ABSTRACT: Recent studies have proposed activation of brown adipose tissue (BAT) thermogenesis as a new strategy to combat obesity. Currently, there is no effective noninvasive imaging agent to directly detect unstimulated BAT and quantify the core mechanism of mitochondrial thermogenesis. We investigated an approach to detect BAT depots and monitor thermogenesis using the mitochondria-targeting voltage sensor radiolabeled fluorobenzyltriphenyl phosphonium (FBnTP). (18)F-FBnTP, (14)C-FBnTP, (18)F-FDG, and (99m)Tc-sestamibi uptake in BAT at room temperature (n = 8) and cold-treated (n = 8) Lewis rats was assayed. The effect of the cold condition on (18)F-FBnTP retention in BAT was assessed in 8 treated and 16 control rats. The effect of the noradrenergic inhibitor propranolol on (14)C-FBnTP response to cold stimulation was investigated in an additional 8 treated and 8 control mice. At room temperature, (18)F-FBnTP accumulated in BAT to an extent similar to that in the heart, second only to the kidney and twice as much as (99m)Tc-sestamibi. Prior exposure to cold (4°C) for 4 h resulted in an 82% decrease of (14)C-FBnTP uptake and an 813% increase of (18)F-FDG uptake in BAT. (99m)Tc-sestamibi uptake was not affected by cold. Administration of (18)F-FBnTP at room temperature 60 min before 120 and 240 min of exposure to cold resulted in marked washout of the tracer from BAT. Propranolol significantly diminished the effect of cold on (14)C-FBnTP and (18)F-FDG uptake into BAT. The intense uptake of (18)F-FBnTP into BAT at room temperature and the response to cold stimulation suggest the unique potential advantage of (18)F-FBnTP not only in detecting unstimulated BAT at high contrast but also in quantifying the mitochondrial thermogenic activity. (18)F-FBnTP PET may serve as a useful technique to assess BAT volume and function.
    Journal of Nuclear Medicine 05/2011; 52(5):808-14. · 5.77 Impact Factor
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    ABSTRACT: The peptide hormone ghrelin mediates through action on its receptor, the growth hormone secretagogue receptor (GHSR), and is known to play an important role in a variety of metabolic functions including appetite stimulation, weight gain, and suppression of insulin secretion. In light of the fact that obesity is one of the major health problems plaguing the modern society, the ghrelin signaling system continues to remain an important and attractive pharmacological target for the treatment of obesity. In vivo imaging of the GHSR could shed light on the mechanism by which ghrelin affects feeding behavior and thus offers a new therapeutic perspective for the development of effective treatments. Recently, a series of piperidine-substituted quinazolinone derivatives was reported to be selective and potent GHSR antagonists with high binding affinities. Described herein is the synthesis, in vitro, and in vivo evaluation of (S)-6-(4-fluorophenoxy)-3-((1-[(11)C]methylpiperidin-3-yl)methyl)-2-o-tolylquinazolin-4(3H)-one ([(11)C]1), a potential PET radioligand for imaging GHSR.
    Bioorganic & medicinal chemistry 02/2011; 19(7):2368-72. · 2.82 Impact Factor
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    ABSTRACT: Recently, A-836339 [2,2,3,3-tetramethylcyclopropanecarboxylic acid [3-(2-methoxyethyl)-4,5-dimethyl-3H-thiazol-(2Z)-ylidene]amide] (1) was reported to be a selective CB2 agonist with high binding affinity. Here we describe the radiosynthesis of [11C]A-836339 ([11C]1) via its desmethyl precursor as a candidate radioligand for imaging CB2 receptors with positron-emission tomography (PET). Whole body and the regional brain distribution of [11C]1 in control CD1 mice demonstrated that this radioligand exhibits specific uptake in the CB2-rich spleen and little specific in vivo binding in the control mouse brain. However, [11C]1 shows specific cerebral uptake in the lipopolysaccharide (LPS)-induced mouse model of neuroinflammation and in the brain areas with Abeta amyloid plaque deposition in a mouse model of Alzheimer's disease (APPswe/PS1dE9 mice). These data establish a proof of principle that CB2 receptors binding in the neuroinflammation and related disorders can be measured in vivo.
    Bioorganic & medicinal chemistry 07/2010; 18(14):5202-7. · 2.82 Impact Factor
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    ABSTRACT: [(18)F] SR144385 and [(18)F] SR147963 were synthesized in a multistep reaction in which fluorine-18 was introduced by nucleophilic halogen displacement on a bromo precursor. The fluorine-18-labeled intermediate was deprotected and coupled with the appropriate alkyl amine to give the final products. Both radioligands had appropriate regional brain distribution for cannabinoid receptors with a target to nontarget ratio of 1.7 for [(18)F] SR147963 and 2.5 for [(18)F] SR144385 at 60 and 90 min postinjection, respectively. The uptake of both tracers was blocked with a 1 mg/kg dose of SR141716A.
    Nuclear Medicine and Biology 12/2000; 27(8):757-62. · 2.52 Impact Factor
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    ABSTRACT: 6-[18F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (6-[18F]fluoro-A-85380 or 6-[18F]FA), a new tracer for positron emission tomography, was synthesized by no-carrier-added [18F] fluorination of 6-iodo-3-((1-tert-butoxycarbonyl-2(S)-azetidinyl)methoxy)pyridine followed by acidic deprotection. 6-[18F]FA followed the regional densities of brain nicotinic acetylcholine receptors (nAChRs) reported in the literature. Evidence of binding to nAChRs and high specificity of the binding in vivo was demonstrated by inhibition with nAChR selective ligands as well as with unlabeled 6-FA. A preliminary toxicology study of the 6-FA showed a relatively low biological effect.
    Nuclear Medicine and Biology 02/2000; 27(1):51-6. · 2.52 Impact Factor
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    ABSTRACT: GR89696, racemic methyl 4-[(3,4-dichlorophenyl)acetyl]-3-[(1-pyrrolidinyl) methyl]-1-piperazinecarboxylate, a kappa opioid receptor ligand, was labeled with [11C]methyl chloroformate. The radiochemical yield was 20% with an observed specific radioactivity of 75.5 GBq/micromol at end of synthesis (2,040 mCi/micromol). Five minutes after intravenous administration, 5.4% of the injected dose accumulated in mouse whole brain. Brain region to cerebellar ratios increased over time with ratios at 90 min of 7.8, 5.6, and 4.5 for the hypothalamus, olfactory tubercle, and striatum, respectively. The uptake of [11C]GR89696 correlated with known kappa opioid receptor densities and was inhibited by kappa opioid selective drugs.
    Nuclear Medicine and Biology 11/1999; 26(7):737-41. · 2.52 Impact Factor
  • Nuclear Medicine and Biology 01/1999; 26(7). · 2.52 Impact Factor
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    ABSTRACT: The feasibility of imaging cerebral opioid receptors by single photon emission computed tomography (SPECT) has been established in baboon using a novel analog of diprenorphine (DPN) radiolabeled with iodine-123. The radioligand, [123I]-O-IA-DPN (C6-O-[123I]iodoallyl-DPN), was prepared in good yield (80%) with high radiochemical purity (>97%) and high specific radioactivity (>2,400 mCi/μmol). In ex vivo autoradiographic studies, with and without naltrexone blockade, [123I]-O-IA-DPN specifically labeled opioid receptors throughout the mouse brain. Nonmetabolized radioligand accounted for >90% of the signal observed in extracts of whole mouse brain. SPECT imaging trials showed that [123I]-O-IA-DPN selectively localized in regions of baboon brain known to have high densities of opioid receptors, such as striatum, thalamus, and temporal cortex. A much lower level of radioligand uptake and retention was noted for cerebellum, a region with few opioid binding sites. Pretreatment with naltrexone (6.5 μmol/kg) blocked [123I]-O-IA-DPN binding in all brain regions. Using naltrexone blockade to define the nonspecific component for a given region of interest, total to nonspecific binding ratios increased linearly (r ≥ 0.98) over the SPECT study with maximal values for striatum (9.8), thalamus (7.1), and temporal cortex (6.9) reached at the last time point investigated (3.5 h). Specific binding for these regions, assessed as the difference between regional SPECT activity for the control and blocked states, proved irreversible over the observation period. By the end of the time course, specific [123I]-O-IA-DPN binding was >85% of total radioactivity in regions rich in opioid receptors and 62% of total radioactivity in cerebellum. The aggregate data are consistent with visualization of multiple opioid receptor types. Thus, [123I]-O-IA-DPN should prove useful for SPECT studies within the constraints imposed by a lack of innate selectivity for a single type of brain opioid receptor. Synapse 29:172–182, 1998. © 1998 Wiley-Liss, Inc.
    Synapse 12/1998; 29(2):172 - 182. · 2.31 Impact Factor
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    ABSTRACT: The in vivo brain regional distribution of 2-[18F]fluoro-A-85380, a novel tracer for positron emission tomographic (PET) studies, followed the regional densities of brain nAChRs reported in the literature. Evidence of binding to nAChRs and high specificity of the binding in vivo was demonstrated by inhibition with nAChR selective ligands as well as with unlabeled 2-fluoro-A-85380. A preliminary toxicology study of the 2-fluoro-A-85380 showed a relatively low biological effect. 2-[18F]Fluoro-A-85380 holds promise as a useful radiotracer for imaging of nAChRs with PET.
    Nuclear Medicine and Biology 11/1998; 25(7):599-603. · 2.52 Impact Factor
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    ABSTRACT: Four halogen-substituted analogues of N-methylepibatidine, a nicotinic acetylcholine receptor (nAChR) ligand, were synthesized. They were (±)-exo-N-methyl-2-(2-halogeno-5-pyridyl)-7-azabicyclo[2.2.1]heptanes, where halogeno = F (1a), Cl (2a), Br (3a), I (4a). (±)-N-Ethylepibatidine (2b) also was synthesized. The compounds 1a, 2a, 3a, and 4a and their corresponding normethyl analogues 1, 2, 3, and 4 inhibited the in vitro binding of [3H]epibatidine to nAChRs to a similar degree, with affinities in the 27−50 pM range. The binding affinity of N-ethylepibatidine (2b), however, was substantially lower. The N-[11C]methyl derivatives of 1, 2, and 3 were synthesized from high-specific radioactivity [11C]methyl iodide using a high-temperature/high-pressure technique. The corresponding radiolabeled compounds [11C]1a, [11C]2a, and [11C]3a were administrated to mice intravenously. The pattern of regional distribution of the three tracers in the mouse brain following intravenous administration matched those of [3H]epibatidine, [3H]norchloroepibatidine, and (±)-exo-2-(2-[18F]fluoro-5-pyridyl)-7-azabicyclo[2.2.1]heptane ([18F]FPH), which are highly specific nAChR probes. The initial brain uptake of the 11C analogues and the acute toxicity of the corresponding authentic nonlabeled compounds appeared to be related to their lipophilicity.
    Journal of Medicinal Chemistry 10/1998; 41(22). · 5.61 Impact Factor
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    ABSTRACT: Up-regulation of brain nicotinic receptors (nAChRs) by chronic nicotine treatment has chiefly been demonstrated by in vitro binding assays. Here, we report that up-regulation of nAChRs in CD-1 mice can be detected using a specific in vivo radioligand for nAChRs, [125I]IPH. After 10 days of (-)-nicotine administration, male and female mice demonstrated a significant elevation of [125I]IPH binding in all brain regions studied. [125I]IPH uptake also displayed significant gender differences with male animals showing a more pronounced increase in [125I]IPH accumulation.
    Synapse 10/1998; 30(1):116-8. · 2.31 Impact Factor
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    ABSTRACT: The present study evaluated short- and long-term effects of MDMA (3,4-methylenedioxymethamphetamine) in the baboon brain using PET and [11C](+)McN 5652, a potent 5-HT transporter ligand, as well as [11C]RTI-55, a cocaine derivative which labels both 5-HT and dopamine transporters. Following baseline PET scans with [11C](+)McN5652, [11C](-)McN5652 (the inactive enantiomer of the active enantiomer [11C](+)McN5652) and [11C]RTI-55, a baboon was treated with MDMA (5 mg/kg, s.c., twice daily for four consecutive days). PET studies at 13, 19, and 40 days post-MDMA revealed decreases in mean radioactivity levels in all brain regions when using [11C](+)McN 5652, but not with [11C](-)McN5652 or [11C]RTI-55. Reductions in specific [11C](+)McN5652 binding (calculated as the difference in radioactivity concentrations between (+) and (-)[11C]McN5652) ranged from 44% in the pons to 89% in the occipital cortex. PET studies at 9 and 13 months showed regional differences in the apparent recovery of 5-HT transporters, with increases in some brain regions (e.g., hypothalamus) and persistent decreases in others (e.g., neocortex). Data obtained from PET studies correlated well with regional 5-HT axonal marker concentrations in the CNS measured after sacrifice of the animal. The results of these studies indicate that PET imaging of the living nonhuman primate brain with [11C](+)McN5652 can detect changes in regional 5-HT transporter density secondary to MDMA-induced neurotoxicity. Using PET, it should also be feasible to use [11C](+)McN5652 to determine whether human MDMA users are also susceptible to MDMA's neurotoxic effects.
    Synapse 07/1998; 29(2):183-92. · 2.31 Impact Factor
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    ABSTRACT: The feasibility of imaging cerebral opioid receptors by single photon emission computed tomography (SPECT) has been established in baboon using a novel analog of diprenorphine (DPN) radiolabeled with iodine-123. The radioligand, [123I]-O-IA-DPN (C6-O-[123I]iodoallyl-DPN), was prepared in good yield (80%) with high radiochemical purity (>97%) and high specific radioactivity (>2,400 mCi/micromol). In ex vivo autoradiographic studies, with and without naltrexone blockade, [123I]-O-IA-DPN specifically labeled opioid receptors throughout the mouse brain. Nonmetabolized radioligand accounted for >90% of the signal observed in extracts of whole mouse brain. SPECT imaging trials showed that [123I]-O-IA-DPN selectively localized in regions of baboon brain known to have high densities of opioid receptors, such as striatum, thalamus, and temporal cortex. A much lower level of radioligand uptake and retention was noted for cerebellum, a region with few opioid binding sites. Pretreatment with naltrexone (6.5 pmol/kg) blocked [123I]-O-IA-DPN binding in all brain regions. Using naltrexone blockade to define the nonspecific component for a given region of interest, total to nonspecific binding ratios increased linearly (r > or = 0.98) over the SPECT study with maximal values for striatum (9.8), thalamus (7.1), and temporal cortex (6.9) reached at the last time point investigated (3.5 h). Specific binding for these regions, assessed as the difference between regional SPECT activity for the control and blocked states, proved irreversible over the observation period. By the end of the time course, specific [123I]-O-IA-DPN binding was >85% of total radioactivity in regions rich in opioid receptors and 62% of total radioactivity in cerebellum. The aggregate data are consistent with visualization of multiple opioid receptor types. Thus, [123I]-O-IA-DPN should prove useful for SPECT studies within the constraints imposed by a lack of innate selectivity for a single type of brain opioid receptor.
    Synapse 06/1998; 29(2):172-82. · 2.31 Impact Factor
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    ABSTRACT: Potent antagonists of bombesin-like peptides have shown great potential for applications in cancer therapy. A 99mTc-labeled agent capable of identifying patients who could benefit from these emerging therapies would have a great impact on patient management. This study involves the synthesis and initial evaluation of technetium diaminedithiolate analogues derived from the potent bombesin analogue Pyr-Gln-Lys-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2 (Lys3-bombesin). We coupled two diaminedithiol (DADT) bifunctional chelating agents (BCAs 1 and 2) to the Lys3 residue at the N-terminal region that is not required for binding to the receptor. 99mTc labeling was performed by ligand exchange on addition of [99mTc]glucoheptonate to a solution of the adduct at room temperature. Two products were obtained from each adduct on analysis by HPLC. The major to minor product ratios of the 99mTc-labeled analogues were 3:1 for products from BCA 1 and 9:1 for the products from BCA 2. Macroscopic amounts of the 99Tc analogues were similarly prepared using [99Tc]glucoheptonate. In this case, the major to minor ratios were 2:1 for the products from both BCAs. For initial evaluation of the binding of the Tc-labeled peptides to bombesin receptors, the 99Tc analogues were used in vitro in competitive binding assays in rat brain cortex membranes against [125I-Tyr4]bombesin. Results of the in vitro assays showed that the inhibition constants (Ki) of the major and minor products were 3.5+/-0.7 and 3.9+/-1.5 nM, respectively, for the products from BCA 1; and 7.4+/-2.0 and 5.2+/-1.5 nM for the products derived from BCA 2, respectively. The high affinity exhibited by these technetium analogues is an indication of their potential for use in non-invasive in vivo biochemical characterization of cancers that possess receptors for bombesin.
    Bioconjugate Chemistry 02/1998; 9(2):218-25. · 4.58 Impact Factor
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    ABSTRACT: The in vivo biodistribution profile of the novel nicotinic acetylcholine receptor (nAChR) radioligand 5-[I-125/123]Iodo-3(2(S)-azetidinylmethoxy)pyridine, [I-125/123]-5-IA, in mouse brain was examined. This radiotracer displayed good brain penetration (3.1% of the injected dose (ID) in whole brain at 15 min post-radioligand injection). Radioligand distribution was consistent with the density of high affinity nAChRs with highest uptake observed in the nAChR-rich thalamus (14.9 %ID/g at 60 min), moderate uptake in cortex (8.5 %ID/g at 60 min), and lowest uptake in the cerebellum (2.4 %ID/g at 60 min). Pretreatment with several different nAChR agonists (A-85380, (-)-nicotine, cytisine) significantly inhibited [I-125]-5-IA binding in all brain regions studied (P < 0.01) demonstrating the high specificity of the radioligand for nAChRs. Blocking doses of the muscarinic antagonist scopolamine and the non-competitive nAChR channel blocker mecamylamine had no significant effect on radioactive uptake supporting the in vitro selectivity of [I-125]-5-IA for the nAChR component of the cholinergic system. [I-125]-5-IA binding sites were shown to be saturable with unlabeled 5-IA. With a relatively low acute toxicity (LD50 > 3 mg/kg via intravenous injection in mice) and high in vivo specificity and selectivity, 5-IA labeled with the imaging radionuclide I-123 may prove useful for single photon emission computed tomography (SPECT) studies of nAChRs in human subjects.
    Life Sciences 02/1998; 62(22):PL 351-7. · 2.56 Impact Factor
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    ABSTRACT: Nalpha-for-Nle-Leu-Phe-Nle-Tyr-Lys, a chemotactic peptide that binds with high affinity to the chemoattractant receptor on granulocytes and monocytes, was labeled with 99mTc using the diaminedithiol (DADT) chelating system to coordinate the Tc. 99mTc labeling of the DADT-coupled peptide was accomplished in 84% overall yield (room temperature for 10 min) using [99mTc]glucoheptonate as the donor of prereduced Tc. HPLC analysis showed two major 99mTc-labeled peptide peaks, 99mTc-DADT-Pep-I and 99mTc-DADT-Pep-II, were obtained in a ratio of 1:0.85. Using an iodoacetamide-derivatized gel to remove unlabeled peptide from the 99mTc labeling mixtures, essentially no-carrier-added (nca) high-specific activity 99mTc-labeled chemotactic peptides were obtained. The 99Tc analogues of the peptides were synthesized (72% yield) in a similar fashion and correlated with 99mTc complexes I and II by HPLC. In vitro competitive receptor binding assays of the isolated 99Tc analogues were performed against the tritiated chemotactic peptide [3H]N-for-Met-Leu-Phe ([3H]fMLF) using isolated granulocytes. The 99Tc-derivatized peptides showed similar binding affinities to the chemoattractant receptor as the unlabeled Nalpha-for-Nle-Leu-Phe-Nle-Tyr-Lys. The nca 99mTc-labeled peptides gave high contrast images of experimental inflammation in rabbits without causing neutropenia. Thus, it is feasible to attach the Tc-DADT chelate to low-molecular weight receptor binding chemotactic peptides and retain substantial binding to the receptor. Chemotactic peptides labeled with 99mTc via the DADT ligand system have the potential for imaging focal sites of inflammation without toxic effects, an important consideration in the successful utilization of chemotactic peptide agonists.
    Bioconjugate Chemistry 01/1998; 9(2):208-17. · 4.58 Impact Factor
  • Synapse 01/1998; 30(1):116-118. · 2.31 Impact Factor
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    ABSTRACT: Nicotinic acetylcholine receptors (nAChRs) have been implicated in a variety of central processes, such as learning and memory and analgesia. These receptors also mediate the reinforcing properties of nicotine in tobacco products and are increased in postmortem samples of brains of smokers. On the other hand, brains of individuals who have died from dementia of the Alzheimer type show abnormally low densities of nAChRs. In this study, the distribution and kinetics of [(+/-)-exo-2-(2-[18F] fluoro-5-pyridyl)-7-azabicyclo[2.2.1]heptane (18F-FPH), a high-affinity nAChR agonist, was evaluated in a baboon using PET. After intravenous injection of 5 mCi [185 MBq] 18F-FPH into a 25-kg anesthetized baboon, sequential quantitative tomographic data were acquired over a period of 150 min. Regions of interest were placed and time-activity curves were generated. Brain kinetics of the radiotracer were calculated, and the in vivo regional binding in the baboon brain was compared with the known in vitro regional distribution of nAChRs in the rat and human brain. Brain activity reached a plateau within 60 min after injection of the tracer, and the binding was reversible. Elimination of 18F-FPH was relatively rapid from the cerebellum (clearance t[1/2] = 3 hr), intermediate from the hypothalamus/midbrain (t[1/2] = 7 hr) and slow from the thalamus (t[1/2] = 16 hr). Radioactivity due to 18F-FPH at 130 min postinjection was highest in the thalamus and hypothalamus/midbrain, intermediate in the neocortex and hippocampus and lowest in the cerebellum. Subcutaneous injection of 1 mg/kg cytisine 45 min after injection of the radiotracer reduced brain activity at 130 min by 67%, 64%, 56% and 52% of control values in the thalamus, hypothalamus/midbrain, hippocampus and cerebellum, respectively. The regional binding of 18F-FPH at 130 min was highly correlated with the known densities of nAChR measured in vitro in human (r = 0.81) and rat brain (r = 0.90). These results demonstrate the feasibility of imaging nAChRs in vivo. Fluorine-18-FPH appears to be a suitable tracer to study nAChRs in the human brain.
    Journal of Nuclear Medicine 12/1997; 38(11):1737-41. · 5.77 Impact Factor
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    ABSTRACT: Tomographic imaging of central nicotinic acetylcholine receptors (nAChRs) via single photon emission computed tomography (SPECT) has been hampered by the lack of a radioligand with suitable in vivo binding characteristics. Therefore, a novel analog of epibatidine, (+/-)-exo-2-(2-iodo-5-pyridyl)-7-azabicyclo[2.2.1]heptane (IPH), labeled with [(125)I] or [(123)I] was evaluated as an in vivo marker of central nicotinic acetylcholine receptors (nAChRs). [(125)I]IPH showed substantial brain penetration (4.2% of the injected dose at 30 min) and a cerebral biodistribution in mice consistent with the in vivo labeling of nAChRs (% injected dose/gram of thalamus, superior colliculi > cerebellum). [(125)I]IPH binding sites were shown to be saturable with unlabeled IPH (ED50 approximately 1 microg/kg). The uptake of [(125)I]IPH was blocked significantly by the nicotinic agonists, cytisine, lobeline, and (-)-nicotine, but not by the noncompetitive nAChR antagonist, mecamylamine. Antagonists of muscarinic (scopolamine), serotonin (ketanserin), and opioid (naloxone) receptors had no significant effect on [(125)I]IPH binding. A preliminary SPECT imaging study with [(123)I]IPH in a baboon showed [(123)I]IPH to localize in nAChR-rich areas of brain (thalamus > frontal cortex > cerebellum). [(123)I]IPH binding in baboon brain was also displaced (35-45% displacement) by a challenge dose of cytisine showing that a well-characterized nicotinic agonist effectively competes for [(123)I]IPH binding sites. [(123)I]IPH seems well suited for imaging studies of nAChRs and, to our knowledge, is the first SPECT agent that has allowed for the visualization of nAChRs in primate brain.
    Synapse 09/1997; 26(4):392-9. · 2.31 Impact Factor

Publication Stats

429 Citations
71.87 Total Impact Points

Institutions

  • 1999–2010
    • Johns Hopkins Medicine
      • Division of Nuclear Medicine
      Baltimore, MD, United States
  • 2000
    • Johns Hopkins University
      • Department of Radiology
      Baltimore, MD, United States
  • 1997–1998
    • National Institute on Drug Abuse
      • Division of Intramural Research (IRP)
      Maryland, United States