Synthesis of 11C-labelled thymidine for tumor visualization using positron emission tomography

Poupeye, E.; Counsell, Raymond E.; Leenheer, A. De; Slegers, Guido; Goethals, Patrick

doi:10.1016/0883-2889(89)90174-3

Cited by 22 publications

(4 citation statements)

References 10 publications

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“…A m : 3 GBq/μmol for [ 11 C]CH 2 O at EOB) . To increase yields and A m and allow for automation, alternative preparations utilizing [ 11 C]CH 3 I were developed and used in clinical tracer productions. ,− To increase yields and A m and allow for automation, alternative preparations utilizing [ 11 C]CH 3 I were developed and used in clinical tracer productions. ,,, In this approach, 5-bromo-2′-deoxyuridine derivatives bearing trimethylsilyl ,, or tetrahydropyranyl ,, hydroxyl protecting groups are lithiated, then 11 C-methylated to produce [ methyl - 11 C]thymidine after protecting group removal (Figure B). Time: 30–35 min.…”

Section: Nucleotides Nucleosides and Nucleobasesmentioning

confidence: 98%

“…702,730−733 To increase yields and A m and allow for automation, alternative preparations utilizing [ 11 C]CH 3 I were developed and used in clinical tracer productions. 731,732,734,735 In this approach, 5-bromo-2′-deoxyuridine derivatives bearing trimethylsilyl 730,733,736 or tetrahydropyranyl 730,733,736 hydroxyl protecting groups are lithiated, then 11 C-methylated to produce [methyl- 11 C]thymidine after protecting group removal (Figure 152B). Time: 30−35 min.…”

Section: Nucleotides Nucleosides and Nucleobasesmentioning

confidence: 99%

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Radiosynthesis, Preclinical, and Clinical Positron Emission Tomography Studies of Carbon-11 Labeled Endogenous and Natural Exogenous Compounds

et al. 2022

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The presence of positron emission tomography (PET) centers at most major hospitals worldwide, along with the improvement of PET scanner sensitivity and the introduction of total body PET systems, has increased the interest in the PET tracer development using the short-lived radionuclides carbon-11. In the last few decades, methodological improvements and fully automated modules have allowed the development of carbon-11 tracers for clinical use. Radiolabeling natural compounds with carbon-11 by substituting one of the backbone carbons with the radionuclide has provided important information on the biochemistry of the authentic compounds and increased the understanding of their in vivo behavior in healthy and diseased states. The number of endogenous and natural compounds essential for human life is staggering, ranging from simple alcohols to vitamins and peptides. This review collates all the carbon-11 radiolabeled endogenous and natural exogenous compounds synthesised to date, including essential information on their radiochemistry methodologies and preclinical and clinical studies in healthy subjects.

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Section: Nucleotides Nucleosides and Nucleobasesmentioning

confidence: 98%

Section: Nucleotides Nucleosides and Nucleobasesmentioning

confidence: 99%

Radiosynthesis, Preclinical, and Clinical Positron Emission Tomography Studies of Carbon-11 Labeled Endogenous and Natural Exogenous Compounds

et al. 2022

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“…After purification, [2- 11 C] thymine and 2′-deoxyribose-1-phosphate are incubated in the presence of thymidine phosphorylase to form [2- 11 C] thymidine. Another synthesis of 11 C thymidine using 11 C MeI has been reported(61). Although sophisticated modeling may be required, several authors have argued that the flux of [2- 11 C] thymidine into DNA can serve as a marker of tumor proliferation(62).…”

Section: Dna Synthesismentioning

confidence: 99%

Exploring Metabolism In Vivo Using Endogenous 11 C Metabolic Tracers

Neumann

Flavell

Wilson

2017

Seminars in Nuclear Medicine

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Cancer and other diseases are increasingly understood in terms of their metabolic disturbances. This thinking has revolutionized the field of ex vivo metabolomics and motivated new approaches to detect metabolites in living systems including proton magnetic resonance spectroscopy (1H-MRS), hyperpolarized 13C MRS, and positron emission tomography (PET). For PET, imaging abnormal metabolism in vivo is hardly new. Positron-labeled small-molecule metabolites have been used for decades in humans, including 18F-FDG, which is used frequently to detect upregulated glycolysis in tumors. Many current 18F metabolic tracers including 18F-FDG have evolved from their 11C counterparts, chemically identical to endogenous substrates and thus approximating intrinsic biochemical pathways. This mimicry has stimulated the development of new radiochemical methods to incorporate 11C and inspired the synthesis of a large number of 11C endogenous radiotracers. This is in spite of the 20-minute half-life of 11C, which generally limits its use in patients to centers with an on-site cyclotron. Innovation in 11C chemistry has persisted in the face of this limitation, because (1) the radiochemists involved are inspired (2) the methods of 11C incorporation are diverse and (3) 11C compounds often show more predictable in vivo behavior, thus representing an important first step in the validation of new tracer concepts. In this mini-review we will discuss some of the general motivations behind PET tracers, rationales for the use of 11C, and some of the special challenges encountered in the synthesis of 11C endogenous compounds. Most importantly, we will try to highlight the exceptional creativity employed in early 11C tracer syntheses, which used enzyme-catalyzed and other “green” methods before these concepts were commonplace.

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“…Synthesis and biological activity of many pyrimidine and purine nucleosides/nucleotides which can be incorporated into DNA/RNA have been reported. [13][14][15][16][17][18] Adenosine and 5-halouracil/uridine are also involved in DNA/ RNA synthesis and are actively taken up by proliferating cells. [19][20][21][22][23][24][25][26][27][28][29][30] In order to enhance biological activity and increase chemical or metabolic stability, a halogen substitution at the C2′ position of the sugar moiety (arabino configuration) has been widely investigated in drug research.…”

Section: Introductionmentioning

confidence: 99%

Assessment of Tumor Cell Proliferation Using [18F]Fluorodeoxyadenosine and [18F]Fluoroethyluracil

Kim

Yang²,

Kim³

et al. 1996

Journal of Pharmaceutical Sciences

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This study was to develop radiofluorinated ethyluracil (FEU) and deoxyadenosine analogues (FAD) for noninvasive assessment of tumor proliferative potential by positron emission tomography (PET). 5-(2-Fluoroethyl)uracil ([18F]FEU) was prepared by treating 2,4-dimethoxy-5-(2-hydroxyethyl)pyrimidine with K18F, followed by hydrolysis with HBr. Fluorodeoxyadenosine ([18F]FAD) was prepared by treating a triacetylated analogue of adenosine with K18F. In vitro cell proliferation assay of [18F]-FEU was performed using human peripheral blood mononucleus cells. Tissue distributions were studied in breast tumor-bearing rats at 0.5, 1, 2 and 4 h along with autoradiography at 45 min postinjection. PET imaging studies were conducted in VX-2 tumor-bearing rabbits. In vitro assay indicated that [18F]FEU incorporated into DNA/RNA during cell proliferation. Tumor-to-tissue count density ratios of [18F]FAD and [18F]-FEU increased as a function of time. [18F]FAD had higher tumor-to-nontumor tissue count density ratios than [18F]FEU. Autoradiograms of [18F]FEU and [18F]FAD, and PET images of [18F]FEU, showed that the tumors could be well visualized. The results suggest that [18F]FEU and [18F]FAD have potential use in evaluating tumor cell proliferation by PET.

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Synthesis of 11C-labelled thymidine for tumor visualization using positron emission tomography

Cited by 22 publications

References 10 publications

Radiosynthesis, Preclinical, and Clinical Positron Emission Tomography Studies of Carbon-11 Labeled Endogenous and Natural Exogenous Compounds

Radiosynthesis, Preclinical, and Clinical Positron Emission Tomography Studies of Carbon-11 Labeled Endogenous and Natural Exogenous Compounds

Exploring Metabolism In Vivo Using Endogenous 11 C Metabolic Tracers

Assessment of Tumor Cell Proliferation Using [18F]Fluorodeoxyadenosine and [18F]Fluoroethyluracil

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