Evaluation of DNA synthesis with carbon-11-labeled 4′-thiothymidine

Abstract

In the cancer research field, the preferred method for evaluating the proliferative activity of cancer cells in vivo is to measure DNA synthesis rates. The cellular proliferation rate is one of the most important cancer characteristics, and represents the gold standard of pathological diagnosis. Positron emission tomography (PET) has been used to evaluate in vivo DNA synthetic activity through visualization of enhanced nucleoside metabolism. However, methods for the quantitative measurement of DNA synthesis rates have not been fully clarified. Several groups have been engaged in research on 4′-[methyl-11C]-thiothymidine (11C-4DST) in an effort to develop a PET tracer that allows quantitative measurement of in vivo DNA synthesis rates. This mini-review summarizes the results of recent studies of the in vivo measurement of cancer DNA synthesis rates using 11C-4DST.

Carbon-11: Radiochemistry and Target-Based PET Molecular Imaging Applications in Oncology, Cardiology, and Neurology

“…402,403 Other tau tracers, such as [ 18 F]T808 and [ 18 F]-FDDNP, showed an affinity for both tau and Aβ. A group synthesized N-[ 11 C]methyl lansoprazole (110), performed a preclinical evaluation, and confirmed the affinity for tau NFTs. 404 A group discovered three novel tau PET tracers, such as [ 11 C]R06924963 (111), [ 11 C]R06931643 (112), and [ 18 F]R06958948.…”

“…FMAU ( 38 ), a pyrimidine analogue radiolabeled with carbon-11, was shown to be useful for tumor cell proliferation imaging. − Although [ 11 C]­thymidine gets easily incorporated into DNA, it also gets catabolized by thymidine phosphorylase, thus complicating the process of image analysis. 4′-[Methyl- 11 C]­thiothymidine ( [ 11 C]­4DST ) ( 39 ), a derivative of thymidine, was developed at the National Institute of Radiological Sciences (NIRS) and was approved for clinical use. , As [ 11 C]­4DST is a nucleoside derivative, it is unable to cross the BBB. Therefore, [ 11 C4DST accumulation in the normal brain is low.…”

PET Molecular Imaging in Drug Development: The Imaging and Chemistry Perspective

“…It is one of the hallmarks of cancer cells. The first radiotracer developed was [ 11 C]thymidine to measure the proliferative rates in different tumors ( 105 ). The large neutral amino acid transporters (LAT) like LAT1, LAT2, LAT3, and LAT4 are highly upregulated in tumor cells due to the full utilization of these transporters for tumor growth and development ( 106 ).…”

Amino Acid and Proliferation PET/CT for the Diagnosis of Multiple Myeloma

“…11 C-4DST is synthesized with up to 70% decay-corrected yields (56). Based on clinical investigation, the optimal timing for scanning of 11 C-4DST PET/CT was 20-40 min after its administration (56).…”

“…11 C-4DST is synthesized with up to 70% decay-corrected yields (56). Based on clinical investigation, the optimal timing for scanning of 11 C-4DST PET/CT was 20-40 min after its administration (56). All the 11 C-4DST PET/CT studies for the assessment of malignancy in our facility were made consistent to start the PET/CT scan from 40 min after the administration of 11 C-4DST.…”