Paige Finley

Johns Hopkins Medicine, Baltimore, MD, United States

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Publications (25)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: Objectives: This study examined Warburg’s hypothesis that mitochondria of cancer cells are constitutively defective. FBnTP is an accurate marker of the mitochondrial membrane potential ({Delta}{Psi}m) - a comprehensive correlate of OXPHOS. The co-distribution of FBnTP and FDG was analyzed in vitro (MCF-7 cells) and in vivo (RMT). Methods: In vitro - the effect of 24-hrs of hypoxia (2% O2) was studied in MCF-7 cells co-incubated with C-14-FBnTP and F-18FDG. In vivo - C-14-FBnTP and F-18-FDG were co-administered IV in Lewis rats bearing mammary tumors (n = 10). Tracers uptake was assayed by counting gamma and beta radioactivity and autoradiography, and compared to staining for blood flow (Hoechst) and hypoxia (pimonidazol, PIMO). Results: Hypoxia induced decreased FBnTP and increased FDG uptake in MCF-7 cells. In RMT, FBnTP distribution in tumor was strictly confined to normoxic regions with high blood flow as demonstrated by the inverse and direct spatial and quantitative relationship with PIMO and Hoechst. In contrast, increased FDG uptake was observed in hypoxic regions with low blood flow. Consequently, FBnTP and FDG demonstrated complementary distribution in the tumor tissue. However, in some tumor regions, FDG distribution was more uniform, which may overlap regions of high FBnTP binding. Quantitatively, a direct correlation was found between FBnTP and FDG in hypoxic regions, but an inverse relationship in normoxic ones. Conclusions: This study demonstrates for the first time the spatial and quantitative complementary relationship of aerobic and anaerobic metabolism in vitro and in tumor tissue. It provides evidence that Warburg’s effect is valid for discrete tumor regions only, probably as an adaptive response to hypoxic microenvironments. These data suggest that targeting {Delta}{Psi}m using PET biomarkers is a successful strategy for non-invasive analysis of the metabolic profile of solid tumors, which may afford valuable prognostic information, when combined with FDG
    SNM 2011; 01/2011
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    ABSTRACT: Objectives: The thermogenic response of BAT has been implicated in energy balance and obesity. The mitochondrial uncoupling protein 1 (UCP1) is responsible for BAT thermogenesis and its activity is correlated linearly with decline of the organelle’s membrane potential ({Delta}{Psi}m). Targeting {Delta}{Psi}m may enable a direct and more accurate estimate of BAT thermogenesis than that afforded by FDG. Here we characterize the voltage sensor FBnTP as marker of BAT thermogensis and investigate its relationship with FDG. Methods: C-14-FBnTP, F-18-FDG and Tc-99m-MIBI biodistribution in BAT was quantified by direct tissue counting and autoradiography in Lewis rats (n = 16) under cold (40C) and room temperature (RT, 220C) with and without IP administration (5 mg/kg) of the adrenergic agonist propranolol (PROP). Results: At RT, FBnTP demonstrated intense uptake in BAT, greater than in heart. Four hours of cold resulted in a significant decrease (>75%) of FBnTP uptake in BAT, but a marked increase (3 to 5-fold) of FDG uptake. There was no change in MIBI uptake after exposure to cold. Inhibition of the adrenergic system, using PROP prevented the cold-induced decrease of FBnTP and increase of FDG uptake in BAT. The cold also affected FBnTP and FDG uptake in organs other than BAT. Conclusions: This study provides evidence that it is feasible to use FBnTP as a marker to explore thermodynamic mechanisms of brown adipocytes. For the first time, FBnTP makes it possible to unravel, in the intact organ, the UCP1-mediated dynamic inverse relationship of mitochondria bioenergetics and glucose metabolism as the underlying mechanism of BAT thermogensis. The combined use of FBnTP and FDG in BAT may serve as a model for studying relationship of glucose metabolism and mitochondrial oxidative activity relevant to cancer. PET imaging studies are in progress
    SNM 20111; 01/2011
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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 10/1999; 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

Publication Stats

452 Citations
71.87 Total Impact Points

Institutions

  • 1999–2011
    • 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