Evaluation of [11C]hemicholinium-15 and [18F]hemicholinium-15 as new potential PET tracers for the high-affinity choline uptake system in the heart

Gao, Mingzhang; Miller, Michael A.; DeGrado, Timothy R.; Mock, Bruce H.; Lopshire, John C.; Rosenberger, Joshua G.; Dusa, Cristian; Das, Mithilesh K.; Groh, William J.; Zipes, Douglas P.; Hutchins, Gary D.; Zheng, Qi

doi:10.1016/j.bmc.2006.11.014

Cited by 21 publications

(4 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Deficiency in high affinity choline uptake (HACU) by the high affinity choline transporter (HAChT) and the loss of vesicular acetylcholine transporter (VAChT), are two characteristic neurochemical changes in AD. High affinity choline uptake transporter can serve as a useful marker of the functional status of the cholinergic presynaptic terminals and is known to be associated with a variety of diseases, such as Parkinson's disease, Alzheimer's disease, coronary heart diseases, tumor cancers (8,9). Thus, choline transporter systems provide attractive targets for the development of PET biomarkers to probe brain, heart, and cancer diseases.…”

Section: Syntheses and In-vitro Evaluation Of Tetrahydroaminoacridinementioning

confidence: 99%

Syntheses and In-vitro Evaluation of Tetrahydroaminoacridine (THA) Based Analogues as High Affinity Choline Transporter (HAChT) Imaging Probe

Azim

Kozaka

Uno

et al. 2016

Bangladesh J. Nuclear Med.

View full text Add to dashboard Cite

HAChT antagonist [ 3 H]HC-3 in rat cerebral membrane. The percentage of inhibition against the binding of [ 3 H]HC-3 to HAChT were calculated using GraphPad Prism v4 software.Results:Hemicholinium-3 showed affinity for HAChT (IC 50 = 20 nM) in the invitro binding assay. A very insignificant inhibition activity (IC 50 = 1000 nM) of Tacrine was revealed. The newly synthesized tacrine derivatives, DMTA and PTAA did not show any affinity for HAChT. Although MKC-231 was reported to enhance cholinergic activity at synaptic terminals, it did not show any affinity for the HAChT in [ 3 H]HC-3 binding assay. ABSTRACT Introduction: In cholinergic neurons, high affinity choline uptake (HACU) by the high affinity choline transporter (HAChT) is a rate-limiting and regulatory step for the synthesis of Acetylcholine (Ach).Thus, HAChT appear to be a relatively specific presynaptic marker for cholinergic neurons in Alzheimer's disease.Objectives: The principle objective of the study is to check the affinity of tetrahydroaminoacridine (THA) derivatives for HAChT. Another objective of the research work is to clarify whether the hemicholinium-3 (ChT inhibitor) and HACU enhancer molecules share the same binding sites or not. Materials and Methods: The inhibition activities of tacrine, the 2,3-dimethylfuran derivative of tacrine (DMTA) and their corresponding 2-oxo-1-pyrrolidineacetyl derivatives, namely PTAA and MKC-231 were measured by displacement of a typical HAChT antagonist [ 3 H]HC-3 in rat cerebral membrane. The percentage of inhibition against the binding of [ 3 H]HC-3 to HAChT were calculated using GraphPad Prism v4 software.Results: Hemicholinium-3 showed affinity for HAChT (IC 50 = 20 nM) in the in vitro binding assay. A very insignificant inhibition activity (IC 50 = 1000 nM) of Tacrine was revealed. The newly synthesized tacrine derivatives, DMTA and PTAA did not show any affinity for HAChT. Although MKC-231 was reported to enhance cholinergic activity at synaptic terminals, it did not show any affinity for the HAChT in [ 3 H]HC-3 binding assay. Conclusion: In vitro [ 3 H]HC-3 binding assay revealed no affinity of MKC-231, tacrine and its corresponding2-oxo-1pyrrolidineacetate derivative towardsHAChT. So, it is worthy to develop radiolabeled HC-3 derivatives with high affinity for HAChT, which can diffuse the BBB, to enable the in vivo investigation of HACU system.

show abstract

Section: Syntheses and In-vitro Evaluation Of Tetrahydroaminoacridinementioning

confidence: 99%

Syntheses and In-vitro Evaluation of Tetrahydroaminoacridine (THA) Based Analogues as High Affinity Choline Transporter (HAChT) Imaging Probe

Azim

Kozaka

Uno

et al. 2016

Bangladesh J. Nuclear Med.

View full text Add to dashboard Cite

show abstract

“…Although previously several electrophilic monofluoromethylations of oxygen-, sulphur-, nitrogen-, and carbon nucleophiles have been reported with CH 2 FI [49][50][51], CH 2 FBr [52][53][54][55][56][57][58], CH 2 FCl [56,[59][60][61], or CH 2 FOSO 2 R (R = CF 3 , CH 3 , tolyl) [55,62] as monofluoromethylating agents, their use was restricted to 18 F-labelling.…”

Section: A-fluoromethyl Ethersmentioning

confidence: 99%

New trends in the chemistry of α-fluorinated ethers, thioethers, amines and phosphines

Manteau

Pazenok

Vors

et al. 2010

Journal of Fluorine Chemistry

358

View full text Add to dashboard Cite

“…(4)). However, the authors reported that the in vivo evaluation of [ 11 C]HC-15 displayed nonspecific binding in heart; there is no report that [ 11 C]HC-15 has been evaluated in cancer [58]. …”

Section: The High-affinity Choline Uptake System (Hacu)mentioning

confidence: 99%

C-11 Radiochemistry in Cancer Imaging Applications

Mach

2010

CTMC

View full text Add to dashboard Cite

Carbon-11 (C-11) radiotracers are widely used for the early diagnosis of cancer, monitoring therapeutic response to cancer treatment, and pharmacokinetic investigations of anticancer drugs. PET imaging permits non-invasive monitoring of metabolic processes and molecular targets, while carbon-11 radiotracers allow a "hot-for cold" substitution of biologically active molecules. Advances in organic synthetic chemistry and radiochemistry as well as improved automated techniques for radiosynthesis have encouraged investigators in developing carbon-11 tracers for use in oncology imaging studies. The short half-life of carbon-11 (20.38 minutes) creates special challenges for the synthesis of C-11 labeled tracers; these include the challenges of synthesizing C-11 target compounds with high radiochemical yield, high radiochemical purity and high specific activity in a short time and on a very small scale. The optimization of conditions for making a carbon-11 tracer include the late introduction of the C-11 isotope, the rapid formation and purification of the target compound, and the use of automated systems to afford a high yield of the target compound in a short time. In this review paper, we first briefly introduce some basic principles of PET imaging of cancer; we then discuss principles of carbon-11 radiochemistry, focus on specific advances in radiochemistry, and describe the synthesis of C-11 radiopharmaceuticals developed for cancer imaging. The carbon-11 radiochemistry approaches described include the N,O, and S-alkylations of [(11)C]methyl iodide/[(11)C]methyl triflate and analogues of [(11)C]methyl iodide and their applications for making carbon-11 tracers; we then address recent advances in exploring a transmetallic complex mediated [(11)C]carbonyl reaction for oncologic targets.

show abstract

Evaluation of [11C]hemicholinium-15 and [18F]hemicholinium-15 as new potential PET tracers for the high-affinity choline uptake system in the heart

Cited by 21 publications

References 15 publications

Syntheses and In-vitro Evaluation of Tetrahydroaminoacridine (THA) Based Analogues as High Affinity Choline Transporter (HAChT) Imaging Probe

Syntheses and In-vitro Evaluation of Tetrahydroaminoacridine (THA) Based Analogues as High Affinity Choline Transporter (HAChT) Imaging Probe

New trends in the chemistry of α-fluorinated ethers, thioethers, amines and phosphines

C-11 Radiochemistry in Cancer Imaging Applications

Contact Info

Product

Resources

About