Synthesis and Evaluation in Monkey of [18F]4-Fluoro-N-methyl-N-(4-(6-(methylamino)pyrimidin-4-yl)thiazol-2-yl)benzamide ([18F]FIMX): A Promising Radioligand for PET Imaging of Brain Metabotropic Glutamate Receptor 1 (mGluR1)

Xu, Rong; Zanotti‐Fregonara, Paolo; Zoghbi, Sami S.; Gladding, Robert L.; Woock, Alicia E.; Innis, Robert B.; Pike, Victor W.

doi:10.1021/jm4012017

Cited by 33 publications

(34 citation statements)

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“…Peak radioactivity uptakes in all regions were followed by a smooth decrease in radioactivity level, for example, in receptor-rich cerebellum by 32% to 5.74 SUV at 85 min after injection. This rate of decrease was close to that previously reported for [ 18 F]FIMX (37% at 90 min after injection) [21]. Summed PET images (Fig.…”

Section: Resultssupporting

confidence: 90%

“…Summed PET images (Fig. 3, upper row) reflected the expected distribution of mGluR1 receptors, as previously seen with [ 18 F]FIMX [21]. …”

Section: Resultssupporting

confidence: 72%

“…1). With appropriate correction for this instability, the logD of [ 11 C]FIMX was found to be 3.27 ± 0.03 ( n = 6), and appreciably higher than the value (2.52) [21] that had been obtained without this correction.…”

Section: Resultsmentioning

confidence: 65%

“…This precursor carries a Boc protecting group at the pyrimidinyl N -methyl group so that only the secondary N -methylamino group on the thiazole ring may be involved in the coupling reaction. The reported synthesis of [ 18 F]FIMX [21] uses a similarly protected precursor, showing that this protecting group may be removed within minutes. Precursor 3 was obtained in moderate overall yield in three steps from commercially available 1 .…”

Section: Resultsmentioning

confidence: 99%

“…Thus, [ 11 C]ITMM showed moderate brain uptake in humans and slow kinetics, which impair attempts at robust quantification [24]. By contrast, we have found that the much higher-affinity ( IC 50 = 1.8 nM) mGluR1 radioligand [ 18 F]FIMX ([ 18 F]4-fluoro- N -methyl- N -(4-(6-(methylamino)pyrimidin-4-yl)thiazol-2-yl)benzamide; Chart 1) has excellent PET imaging characteristics for mGluR1 quantification both in monkey [21] and in human [25], including high brain uptake, high receptor-specific signal and quantifiable reversible kinetics.…”

Section: Introductionmentioning

confidence: 99%

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[ carbonyl - 11 C]4-Fluoro- N -methyl- N -(4-(6-(methylamino)pyrimidin-4-yl)thiazol-2-yl)benzamide ([ 11 C]FIMX) is an effective radioligand for PET imaging of metabotropic glutamate receptor 1 (mGluR1) in monkey brain

Hong

et al. 2015

Nuclear Medicine and Biology

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Introduction Metabotropic glutamate subtype receptor 1 (mGluR1) is implicated in several neuropsychiatric disorders and is a target for drug development. [18F]FIMX ([18F]4-fluoro-N-methyl-N-(4-(6-(methylamino)pyrimidin-4-yl)thiazol-2-yl)benzamide) is an effective radioligand for imaging brain mGluR1 with PET. A similarly effective radioligand with a shorter half-life would usefully allow PET studies of mGluR1 at baseline and after pharmacological or other challenge on the same day. Here we describe the preparation of [11C]FIMX for evaluation in monkey with PET. Methods [11C]FIMX was prepared via Pd-promoted carbonylation of 1-fluoro-4-iodobenzene with [11C]carbon monoxide, aminolysis of the [11C]acyl-palladium complex with the requisite Boc-protected amine, and deprotection with HCl in THF. PET scans of [11C]FIMX injected into a monkey were performed at baseline and after preblock of mGluR1 with measurement of the arterial input function. Results The radiosynthesis required 42 min and gave [11C]FIMX in about 5% overall decay-corrected radiochemical yield and with a specific activity of about 100 GBq/μmol. PET in rhesus monkey at baseline showed that radioactivity peaked high in receptor-rich cerebellum and much lower in receptor-poor occipital cortex. Radioactivity in cerebellum declined to 32% of peak at 85 min. VT at baseline appeared stable in all brain regions after 60 min. Under mGluR1 pre-blocked condition, radioactivity uptake in all regions declined more rapidly to a low level. Receptor pre-block reduced VT from 13.0 to 1.5 in cerebellum and from 2.9 to 1.4 in occipital cortex. Conclusion [11C]FIMX is an effective radioligand for imaging mGluR1 in monkey with PET.

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Section: Resultssupporting

confidence: 90%

“…Summed PET images (Fig. 3, upper row) reflected the expected distribution of mGluR1 receptors, as previously seen with [ 18 F]FIMX [21]. …”

Section: Resultssupporting

confidence: 72%

Section: Resultsmentioning

confidence: 65%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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[ carbonyl - 11 C]4-Fluoro- N -methyl- N -(4-(6-(methylamino)pyrimidin-4-yl)thiazol-2-yl)benzamide ([ 11 C]FIMX) is an effective radioligand for PET imaging of metabotropic glutamate receptor 1 (mGluR1) in monkey brain

Hong

et al. 2015

Nuclear Medicine and Biology

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Hypervalent Iodine Compounds as Precursors for Biomedical Radiotracers

Telu

Siméon

et al. 2018

Patai's Chemistry of Functional Groups

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This chapter summarizes the increasing role that hypervalent aryliodine compounds, especially aryliodine(III) compounds, are serving as precursors for biomedical radiotracers due to their ease of synthesis, often adequate storage stabilities, and high reactivities in useful labeling reactions, especially those with short‐lived [ 18 F]fluoride ion ( t 1/2 = 109.8 min) for producing radiotracers for imaging with positron emission tomography.

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Fluorine‐18 Radiochemistry for PET Imaging Applications—Fundamentals and Recent Advances

Siméon,

Telu,

Cai

et al. 2024

PATAI'S Chemistry of Functional Groups

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Positron emission tomography (PET) is a major molecular imaging modality with prominent roles in biomedical research, medical diagnosis, and drug development. Underpinning the widespread utility of PET is extensive radiochemistry research on the development of PET radiotracers and efficient methods for their labeling in optimal molecular positions. Fluorine‐18 has gained importance for labeling PET radiotracers because of (i) favorable decay characteristics, including a half‐life of 109.8 min and a high rate of decay by relatively low energy positron emission (β + , 97%), (ii) an established capacity to produce this radioisotope in very high activity and molar activity from modern biomedical cyclotrons, and (iii) versatile radiochemistry that enables late‐stage incorporation of this radionuclide into radiotracers that range in size from small drug‐like molecules through to macromolecules. In this chapter, we survey this rapidly evolving area of fluorine‐18 radiochemistry with regard to its fundamentals and key advances in meeting the major challenges in PET radiotracer development.

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Synthesis and Evaluation in Monkey of [¹⁸F]4-Fluoro-N-methyl-N-(4-(6-(methylamino)pyrimidin-4-yl)thiazol-2-yl)benzamide ([¹⁸F]FIMX): A Promising Radioligand for PET Imaging of Brain Metabotropic Glutamate Receptor 1 (mGluR1)

Cited by 33 publications

References 55 publications

[ carbonyl - 11 C]4-Fluoro- N -methyl- N -(4-(6-(methylamino)pyrimidin-4-yl)thiazol-2-yl)benzamide ([ 11 C]FIMX) is an effective radioligand for PET imaging of metabotropic glutamate receptor 1 (mGluR1) in monkey brain

[ carbonyl - 11 C]4-Fluoro- N -methyl- N -(4-(6-(methylamino)pyrimidin-4-yl)thiazol-2-yl)benzamide ([ 11 C]FIMX) is an effective radioligand for PET imaging of metabotropic glutamate receptor 1 (mGluR1) in monkey brain

Hypervalent Iodine Compounds as Precursors for Biomedical Radiotracers

Fluorine‐18 Radiochemistry for PET Imaging Applications—Fundamentals and Recent Advances

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