18F-fluoro-2′-deoxyuridine as a tracer of nucleic acid metabolism in brain tumors

Abstract

The value of 18F-fluoro-2'-deoxyuridine (18F-FUdR) as a tracer for nucleic acid metabolism was studied using an experimental rat brain-tumor model. The 18F activity in the tumor tissue 45 minutes after intravenous injection of 18F-FUdR was about 12 times higher than that in the contralateral cortex. Double-labeled autoradiography with 18F-FUdR and 14C-thymidine revealed similar brain-tumor images. In contrast, an autoradiographic comparison of 18F-FUdR with 14C-aminoisobutyric acid, which reveals the impairment of the blood-brain barrier, showed very different images. Also, the 18F radioactivity in the tumor tissue was at a constant level for 30 to 120 minutes, whereas a notable increase in 18F activity with time was observed in nucleotides and acid-insoluble fractions. These results suggest that the distribution pattern of 18F-FUdR closely correlates with the metabolism of nucleic acid and that this drug could be a useful tracer for positron emission tomography.

Pioneering and Fundamental Achievements on the Development of Positron Emission Tomography (PET) in Oncology

“…Kiyosawa et al (1986) performed PET imaging of rabbit orbital tumors with 18 F-5-FdUR and clearly visualized the tumor with a high tumor-to-normal orbit ratio. Tsurumi et al (1990) tested the feasibility of 18 F-5-FdUR for PET imaging of nucleic metabolism using a rat brain tumor model. A double tracer autoradiogram with 18 F-5-FdUR and 14 C-thymidine revealed similar brain-tumor images.…”

Metabolic changes of glioma following chemotherapy: an experimental study using four PET tracers

“…From an analysis of 18FUdR accumulation in tumors, Ishiwata et al [19,21] have shown that, 2 hours after administration, 17-34% and 19-24% of 18F are found in, respectively, the acid soluble and nucleotide fractions, indicating that it has entered the nucleic acid synthesis pathway. Tsurumi et al [43] have done autoradiographic and isotope uptake (lSFUdR, ~4C-dThd and ~4C-isobutyric acid) studies using a transplanted glioma model and found that the radioactivity of 18F from tumor tissue remains constant between 30 and 120 rain. In contrast, there is a steady increase in the nucleotide and acid insoluble fractions over time.…”

“…It was shown that nC-methionine could be used to diagnose the malignancy of tumors and to evaluate therapeutic effectiveness [4-6, 10-11, 22, 28, 33]. Thirdly, we have developed ~8F-fluoro-2'-deoxyuridine (18FUdR) as a tracer indicative of the metabolism of nucleic acid [1,18,19,23,24,43]. To shed light on the metabolic changes in gliomas following therapy, we have used a glioma model to study correlational changes in uptake of 18FUdR, 14C-thymidine, 14C-methionine and 3H-deoxyglucose after chemotherapy as a means for interpreting clinical PET results, together with the changes in the bromodeoxyuridine labeling index.…”

The use of Positron Emission Tomography Scanning in Occult and Recurrent Head and Neck Cancer

“…Monoclonal antibodies tagged with I 124 which has a 4-day half life and can therefore allow the imaging of distribution and binding of antibodies which generally requires at least 24 h. Such studies have been done with HMFG1 for epithelial neoplasms (13). In addition, chemotherapeutic agents have been studied such as F 18 fluorine tagged 5-FU and tamoxifen (14,15). Finally, the hypoxic agent misonidazole can be tagged with…”