2012
DOI: 10.1016/j.nucmedbio.2011.12.003
|View full text |Cite
|
Sign up to set email alerts
|

A fast chemoenzymatic synthesis of [11C]-N5,N10-methylenetetrahydrofolate as a potential PET tracer for proliferating cells

Abstract: Introduction Thymidylate synthase (TSase) and folate receptors (FRs) are well developed targets of cancer therapy. Discovery of a simple and fast method for the conversion of 11CH3I to [11C]-formaldehyde (11CH2O) encouraged us to label the co-factor of this enzyme. Preliminary studies conducted on cell lines have demonstrated a preferential uptake of [11-14C]-(R)-N5,N10-methylene-5,6,7,8-tetrahydrofolate (14CH2H4folate) by cancerous cell vs. normal cells from the same organ [1] pointing out 11CH2H4folate as a … Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
1
1

Citation Types

0
16
1

Year Published

2013
2013
2022
2022

Publication Types

Select...
7
1

Relationship

1
7

Authors

Journals

citations
Cited by 9 publications
(17 citation statements)
references
References 18 publications
0
16
1
Order By: Relevance
“…So far, only two reduced folates have been radiolabeled and reported in the literature. Saeed et al developed the radiosynthesis of a N 5 , N 10 -methylenetetrahydrofolate radiotracer labeled with carbon-11, whereas Vaitilingam et al reported on a 99m Tc-labeled N 5 , N 10 -dimethyltetrahydrofolate derivative. , Both groups reported on the synthesis of these radiofolates, but only the 99m Tc-labeled N 5 , N 10 -dimethyltetrahydrofolate radiotracer existing as 1:1 mixture of the 6 R - and 6 S -diastereoisomers was biologically evaluated. Although the organic synthesis of 5-MTHF was reported by Zhou et al in 2013, there are no studies available in the literature to date about the biological behavior of diastereomerically pure 6 S - and 6 R -5-MTHF radiotracers and whether such radiofolates can be used to image FR-positive tissues using PET.…”
Section: Introductionmentioning
confidence: 99%
“…So far, only two reduced folates have been radiolabeled and reported in the literature. Saeed et al developed the radiosynthesis of a N 5 , N 10 -methylenetetrahydrofolate radiotracer labeled with carbon-11, whereas Vaitilingam et al reported on a 99m Tc-labeled N 5 , N 10 -dimethyltetrahydrofolate derivative. , Both groups reported on the synthesis of these radiofolates, but only the 99m Tc-labeled N 5 , N 10 -dimethyltetrahydrofolate radiotracer existing as 1:1 mixture of the 6 R - and 6 S -diastereoisomers was biologically evaluated. Although the organic synthesis of 5-MTHF was reported by Zhou et al in 2013, there are no studies available in the literature to date about the biological behavior of diastereomerically pure 6 S - and 6 R -5-MTHF radiotracers and whether such radiofolates can be used to image FR-positive tissues using PET.…”
Section: Introductionmentioning
confidence: 99%
“…This methodology can be used to generate dihydrofolates labeled in specific positions with stable isotopes with average overall yields of >30%, facilitating many applications in cell biology and mechanistic enzymology. ,,, For the first time, heavy-atom KIEs for the DHFR-catalyzed reduction of H 2 F could be measured to provide strong support for a stepwise reduction of the substrate in which protonation at N5 and hydride transfer from C4 of the NADPH to C6 of protonated dihydrofolate proceed independently. This chemoenzymatic pterin synthesis can be integrated into other enzymatic procedures to generate folate derivatives , and other high-value natural products that are not easily accessible by conventional synthesis . It can be applied to nutritional, medical, and cell-biological research to address questions of in vivo bioavailability and to explore the kinetics of folate metabolism in intact cells and organisms. ,− …”
Section: Discussionmentioning
confidence: 99%
“…Folate and its derivatives can be synthesized by connecting the pterin, p ABA, and glutamate groups in sequential order, and several synthetic strategies to incorporate an isotopic label into pterin in a regiospecific manner have been reported. Pterins have been synthesized by condensing guanidine or dihydroxyacetone with the respective heterocyclic starting materials, and N5-, C2-, and C6-labeled folates have been made previously. , However, because symmetric reagents are used in these syntheses, regioselective isotope labeling of C7 and C9 cannot easily be achieved. , In all cases, the yields of labeled folate or derivatives are low (<5% overall yield), and the procedures depend on multiple purification steps. Chemoenzymatic strategies have also been described, whereby H 4 F was condensed with 11 C-formaldehyde or 14 C-formic acid to yield the corresponding isotopically labeled [ 11 C]­5,10-methylene-H 4 F, [ 14 C]­5-formyl-H 4 F, and [ 14 C]­10-formyl-H 4 F. However, a general and efficient method to label the pterin ring in folates has never been developed.…”
Section: Introductionmentioning
confidence: 99%
“…A selection of radiolabeled reduced folate derivatives reported in the literature is shown in Figure 6. The first reduced folate derivative radiolabeled with a positron emitting radionuclide was a 11 C-labeled compound ([ 11 C]-N 5 ,N 10 -methylene-tetrahydrofolate, 17, Figure 6) reported in 2012, however, neither information regarding the diastereomeric ratio of the radiolabeled product nor biological results were reported [60]. Although not a PET radiotracer, [ 99m Tc]Tc-DMTHF (18, Figure 6), a dimethyltetrahydrofolate derivative reported by Vaitiligam et al [61] is the only reported reduced folate labeled with a SPECT radioisotope.…”
Section: Reduced Folate Derivativesmentioning
confidence: 99%