Dataset Information

Radiosynthesis and reactivity of N-[¹¹C]methyl carbamoylimidazole.

ABSTRACT: N-Methyl carbamoylimidazole is a safe and practical alternative to methyl isocyanate for carbamoylation reactions. We have developed a new chemical route for its synthesis from methyl iodide and applied this to the synthesis of N-[¹¹C]methyl carbamoylimidazole as a new [¹¹C]synthon to radiolabel biomolecules for PET imaging research. N-[¹¹C]methyl carbamoylimidazole was prepared from [¹¹C]methyl iodide in 70-74% radiochemical yield (decay corrected) and can be used in situ for further reaction without purification. The reactivity of N-[¹¹C]methyl carbamoylimidazole was demonstrated in a series of [¹¹C]carbamoylation reactions.

SUBMITTER: Kadirvel M

PROVIDER: S-EPMC6061098 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundThe ?-amyloid radiotracer [11C] PiB is extensively used for the Positron Emission Tomography (PET) diagnosis of Alzheimer's Disease and related dementias. For clinical use, [11C] PiB is produced using the 11C-methylation method ([11C] Methyl iodide or [11C] methyl triflate as 11C-methylation agents), which represents the most employed 11C-labelling strategy for the synthesis of 11C-radiopharmaceuticals. Recently, the use of direct [11C]CO2 fixation for the syntheses of 11C-tracers has gained interest in the radiochemical community due to its importance in terms of radiochemical versatility and for permitting the direct employment of the cyclotron-produced precursor [11C]CO2. This paper presents an optimised alternative one-pot methodology of [11C]CO2 fixation-reduction for the rapid synthesis of [11C] PiB using an automated commercial platform and its quality control.Results[11C] PiB was obtained from a (25.9?±?13.2)% (Average?±?Variation Coefficient, n?=?3) (end of synthesis, decay corrected) radiochemical yield from trapped [11C]CO2 after 1?min of labelling time using PhSiH3 / TBAF as the fixation-reduction system in Diglyme at 150?°C. The radiochemical purity was higher than 95% in all cases, and the molar activity was (61.4?±?1.6) GBq/?mol. The radiochemical yield and activity (EOS) of formulated [11C] PiB from cyclotron-produced [11C]CO2 was (14.8?±?12.1)%, decay corrected) and 9.88?GBq (± 6.0%), respectively. These are higher values compared to that of the 11C-methylation method with [11C]CH3OTf (~?8.3%).ConclusionsThe viability of the system PhSiH3 / TBAF to efficiently promote the radiosynthesis of [11C] PiB via direct [11C]CO2 fixation-reduction has been demonstrated. [11C] PiB was obtained through a fully automated radiosynthesis with a satisfactory yield, purity and molar activity. According to the results, the one-pot methodology employed could reliably yield sufficiently high tracer amounts for preclinical and clinical use.

Project description:Purpose68Ga-labeled fibroblast activation protein inhibitors, such as [68Ga]Ga-DOTA-FAPI-04 and [68Ga]Ga-DOTA-FAPI-46, have been successfully applied in positron emission tomography imaging of various tumor types. To broaden the PET tracers of different positron nuclides for imaging studies of FAP-dependent diseases, we herein report the radiosynthesis and preclinical evaluation of two 11C-labeled FAP inhibitors, 11C-RJ1101 and 11C-RJ1102.MethodsTwo phenolic hydroxyl precursors based on a quinoline amide core coupled with a 2-cyanopyrrolidine moiety were coupled with [11C]CH3I to synthesize 11C-RJ1101 and 11C-RJ1102. In vivo small-animal PET and biological distribution studies of 11C-RJ1101 and 11C-RJ1102 compared to [68Ga]Ga-DOTA-FAPI-04 were conducted in nude mice bearing U87MG tumor xenografts at 30, 60, and 90min, respectively.Results11C-RJ1101 and 11C-RJ1102 were synthesized in over 15% radiochemical yields, with specific activities of 67 GBq/μmol and 34 GBq/μmol, respectively, at the end of synthesis and radiochemical purities greater than 99%. In U87MG tumor xenograft PET studies, the three tracers experienced higher specific uptake at the tumor site. However, because of significant differences in metabolism and clearance, [68Ga]Ga-DOTA-FAPI-04 experienced high uptake in the kidney, whereas 11C-RJ1101 and 11C-RJ1102 showed high uptake in the liver and intestine. Biodistribution studies revealed significant hepatobiliary excretion of 11C-RJ1101 and 11C-RJ1102. 11C-RJ1102 showed higher specific tumor uptake in U87MG xenografts (1.71 ± 0.08% injected dose per Gram of tissue [ID/g]) than 11C-RJ1101 (1.34 ± 0.10%ID/g) and [68Ga]Ga-DOTA-FAPI-04 (1.29 ± 0.04%ID/g) after 30 min p. i. In orthotopic glioma models, the uptake values were 0.07 ± 0.03% ([68Ga]Ga-DOTA-FAPI-04) and 0.16 ± 0.03% (11C-RJ1102), respectively.Conclusion11C-RJ1101 and 11C-RJ1102 are interesting candidates for translation to the clinic, taking advantage of the shorter half-life and physical imaging properties of C-11.

Dataset Information

Radiosynthesis and reactivity of N-[¹¹C]methyl carbamoylimidazole.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Radiosynthesis and reactivity of N-[11C]methyl carbamoylimidazole.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Radiosynthesis and reactivity of N-[¹¹C]methyl carbamoylimidazole.