scholarly journals Radiochemical Synthesis and Evaluation in Non-Human Primates of 3-[11C]methoxy-4-aminopyridine: A Novel PET Tracer for Imaging Potassium Channels in the CNS

2021 ◽  
Vol 12 (4) ◽  
pp. 756-765
Author(s):  
Nicolas J. Guehl ◽  
Ramesh Neelamegam ◽  
Yu-Peng Zhou ◽  
Sung-Hyun Moon ◽  
Maeva Dhaynaut ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Pet Tracer ◽  
Radiochemical Synthesis

scholarly journals Structure-activity relationship studies of three novel 4-aminopyridine K+ channel blockers

2019 ◽  
Author(s):  
Sofia Rodríguez-Rangel ◽  
Alyssa D. Bravin ◽  
Karla M. Ramos-Torres ◽  
Pedro Brugarolas ◽  
Jorge E. Sánchez-Rodríguez
Keyword(s):  
Multiple Sclerosis ◽  
Potassium Channels ◽  
Symptomatic Treatment ◽  
K Channel ◽  
Channel Blockers ◽  
Rodent Models ◽  
Voltage Gated ◽  
Structure Activity ◽  
Pet Tracer ◽  
Ph Conditions

Abstract4-Aminopyridine (4AP) is a specific blocker of voltage-gated potassium channels (KV1 family) clinically approved for the symptomatic treatment of patients with multiple sclerosis (MS). It has recently been shown that [18F]3F4AP, a radiofluorinated analog of 4AP, also binds to KV1 channels and can be used as a PET tracer for the detection of demyelinated lesions in rodent models of MS. Here, we investigate three novel 4AP derivatives containing methyl (-CH3), methoxy (-OCH3) and trifluoromethyl (-CF3) in the 3 position as potential candidates for PET imaging and/or therapy. We characterized the physicochemical properties of these compounds (pKa and logD) and analyzed their ability to block Shaker K+ channel under different voltage and pH conditions. Our results demonstrate that all three derivatives are able to block voltage-gated potassium channels. Specifically, 3-methyl-4-aminopyridine (3Me4AP) was found to be approximately 7-fold more potent than 4AP, whereas the methoxy (3MeO4AP) and trifluoromethyl (3CF34AP) containing compounds were about 3- to 4-fold less potent than 4AP, respectively. These results suggest that these novel derivatives are potential candidates for therapy and imaging.

scholarly journals Automated Radiochemical Synthesis of [18F]3F4AP: A Novel PET Tracer for Imaging Demyelinating Diseases

10.3791/55537 ◽  
2017 ◽  
Author(s):  
Pedro Brugarolas ◽  
Mohammed Bhuiyan ◽  
Anna Kucharski ◽  
Richard Freifelder
Keyword(s):  
Demyelinating Diseases ◽  
Pet Tracer ◽  
Radiochemical Synthesis

scholarly journals Structure-activity relationship studies of four novel 4-aminopyridine K+ channel blockers

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sofia Rodríguez-Rangel ◽  
Alyssa D. Bravin ◽  
Karla M. Ramos-Torres ◽  
Pedro Brugarolas ◽  
Jorge E. Sánchez-Rodríguez
Keyword(s):  
Multiple Sclerosis ◽  
Potassium Channels ◽  
Symptomatic Treatment ◽  
K Channel ◽  
Channel Blockers ◽  
Rodent Models ◽  
Voltage Gated ◽  
Structure Activity ◽  
Pet Tracer ◽  
Ph Conditions

Abstract4-Aminopyridine (4AP) is a specific blocker of voltage-gated potassium channels (KV1 family) clinically approved for the symptomatic treatment of patients with multiple sclerosis (MS). It has recently been shown that [18F]3F4AP, a radiofluorinated analog of 4AP, also binds to KV1 channels and can be used as a PET tracer for the detection of demyelinated lesions in rodent models of MS. Here, we investigate four novel 4AP derivatives containing methyl (-CH3), methoxy (-OCH3) as well as trifluoromethyl (-CF3) in the 2 and 3 position as potential candidates for PET imaging and/or therapy. We characterized the physicochemical properties of these compounds (basicity and lipophilicity) and analyzed their ability to block Shaker K+ channel under different voltage and pH conditions. Our results demonstrate that three of the four derivatives are able to block voltage-gated potassium channels. Specifically, 3-methyl-4-aminopyridine (3Me4AP) was found to be approximately 7-fold more potent than 4AP and 3F4AP; 3-methoxy- and 3-trifluoromethyl-4-aminopyridine (3MeO4AP and 3CF34AP) were found to be about 3- to 4-fold less potent than 4AP; and 2-trifluoromethyl-4-AP (2CF34AP) was found to be about 60-fold less active. These results suggest that these novel derivatives are potential candidates for therapy and imaging.

The Influence of Polysorbate 80 on the Radiochemical Synthesis of a PET Tracer in the FASTlab

2014 ◽  
Vol 32 (4) ◽  
pp. 1425-1437
Author(s):  
Wai Lam Yip ◽  
Sverre Arne Sande ◽  
David Grace ◽  
Dirk Jan in’t Veld ◽  
Per Christian Sontum ◽  
...  
Keyword(s):  
Polysorbate 80 ◽  
Pet Tracer ◽  
Radiochemical Synthesis

Comparison of diagnostic accuracy of 18F-FDG PET, 123I-IMT- and 99mTc-MIBI SPECT

2006 ◽  
Vol 45 (01) ◽  
pp. 49-56 ◽  
Author(s):  
N. Özdemir-Sahin ◽  
P. Hipp ◽  
W. Mier ◽  
M. Eisenhut ◽  
J. Debus ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Fdg Pet ◽  
Tumour Progression ◽  
Roc Curves ◽  
Low Grade ◽  
Who Grade ◽  
Pet Tracer ◽  
Patient Groups ◽  
99Mtc Mibi ◽  
Mibi Spect

Summary Aim was to evaluates the diagnostic accuracy of the SPECTtracers 3-123I-α-methyl-L-tyrosine (IMT) and 99mTc(I)- hexakis(2-methoxyisobutylisonitrile) (MIBI) as well as the PET-tracer 2-18F-2-deoxyglucose (FDG) for detecting tumour progression in irradiated low grade astrocytomas (LGA). Patients, methods: We examined 91 patients (56 males; 35 females; 44.7 ± 11.5 years), initially suffering from histologically proven LGAs (mean WHO grade II) and treated by stereotactic radiotherapy (59.0 ± 4.6 Gy). On average 21.9 ± 11.2 months after radiotherapy, patients presented new Gd-DTPA enhancing lesions on MRI, which did not allow a differentiation between progressive tumour (PT) and non-PT (nPT) at this point of time. PET scans (n=82) were acquired 45 min after injection of 208 ± 32 MBq FDG. SPECT scans started 10 min after injection of 269 ± 73 MBq IMT (n=68) and 15 min after injection of 706 ± 63 MBq MIBI (n=34). Lesions were classified as PT and nPT based on prospective follow-up (clinically, MRI) for 17.2 ± 9.9 months after PET/SPECT. Lesion-to-normal ratios (L/N) were calculated using contra lateraly mirrored reference regions for the SPECT examinations and reference regions in the contra lateral grey (GM) and white matter (WM) for FDG PET. Ratios were evaluated by Receiver Operating Characteristic (ROC) analysis. Results: In the patient groups nPT and PT, L/N ratios for FDG (GS) were 0.6 ± 0.3 vs. 1.2 ± 0.5 (p = 0.003), for FDG (WS) 1.2 ± 0.4 vs. 2.6 ± 0.4 (p <0.001), for IMT 1.1 ± 0.1 vs. 1.8 ± 0.4 (p <0.001) and for MIBI 1.6 ± 0.7 vs. 2.6 ± 2.2 (p = 0.554). Areas under the non-parametric ROC-curves were: 0.738 ± 0.059 for FDG (GS), 0.790 ± 0.057 for FDG (WS), 0.937 ± 0.037 for IMT and 0.564 ± 0.105 for MIBI. Conclusion: MIBI-SPECT examinations resulted in a low accuracy and especially in a poor sensitivity even at modest specificity values. A satisfying diagnostic accuracy was reached with FDG PET. Using WM as reference region for FDG PET, a slightly higher AUC as compared to GM was calculated. IMT yielded the best ROC characteristics and the highest diagnostic accuracy for differentiating between PT and nPT in irradiated LGA.

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