¹⁸F-5-fluorouridine, A New Probe For Measuring The Proliferation Of Tissue in vivo

1. (1)|Increased metabolic trapping of labeled fluorouridine reflects the interaction of three parameters in rapidly proliferating tissues: increased rates of intracellular phosphorylation, increased rates of transport, and increased rates of synthesis of RNA. 2. (2)|We have taken advantage of these metabolic phenomena, demonstrating in this paper that the uptake of ¹⁸F-5-fluorouridine, a positron-emitting radiopharmaceutical, can provide a very practical means for measuring changes in proliferative states of tissues in vivo. 3. (3)|Two major changes in proliferative states have been examined: one involves changes in growth of normal mouse tissues induced by pharmacological agents; the other involves tumor growth and neoplastic infiltration in mice and rabbits. 4. (4)|We describe tracer experiments with ¹⁸F-5-fluorouridylate, prepared by enzymatic means, and with ¹⁸F-5-fluorouridine, prepared by both enzymatic means and direct radiochemical procedures. 5. (5)|Uptakes of ¹⁸F after a pulse of ⁸F-5-fluorouridine were increased in mouse spleen following phenylhydrazine treatment to induce increased splenic erythropoiesis. 6. (6)|Uptakes of ¹⁸F in various mouse tissues were decreased following pretreatment with actinomycin D. This finding is consistent with the known inhibitory action of actinomycin on RNA synthesis. 7. (7)|Intracerebral Zimmerman ependymoblastoma tumors showed extra-ordinarily high uptakes of fluorine-18 in mice injected intravenously with ¹⁸F-5-fluorouridylate or with ¹⁸F-5-fluorouridine in contrast to very low uptakes by normal brain tissue. 8. (8)|After intracerebral injection of mice with suspensions of L1210 leukemia cells, distant organs such as lung, liver, and spleen became involved. These tissues showed significant increases of radioactivity after pulse labeling with ¹⁸F-5-fluorouridylate consistent with histological evidence for infiltration of these tissues by neoplastic cells. 9. (9)|Intramuscular VX2 carcinoma tumors in rabbits showed localized uptakes of ¹⁸F significantly higher than surrounding normal muscle tissue. 10. (10)|The most important clinical implication of the present work is the promise that ¹⁸F-5-fluorouridine uptakes can be followed in humans by positron emission tomography. This would provide a direct means of measuring different rates of in vivo proliferation in neoplasms, hematologic tissues and other organs undergoing rapid growth changes.