Crawford E J, Friedkin M, Wolf A P, Fowler J S, Gallagher B M, Lambrecht R M, MacGregor R R, Shiue C Y, Wodinsky I, Goldin A
Adv Enzyme Regul. 1982;20:3-22. doi: 10.1016/0065-2571(82)90005-x.
(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) 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) 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) 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) Uptakes of 18F after a pulse of 18F-5-fluorouridine were increased in mouse spleen following phenylhydrazine treatment to induce increased splenic erythropoiesis. (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) Intracerebral Zimmerman ependymoblastoma tumors showed extraordinarily 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) 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) Intramuscular VX2 carcinoma tumors in rabbits showed localized uptakes of 18F significantly higher than surrounding normal muscle tissue. (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.
(1) 标记的氟尿苷代谢捕获增加反映了快速增殖组织中三个参数的相互作用：细胞内磷酸化速率增加、转运速率增加和RNA合成速率增加。(2) 我们利用了这些代谢现象，在本文中证明，正电子发射放射性药物18F-5-氟尿苷的摄取可以为测量体内组织增殖状态的变化提供一种非常实用的方法。(3) 已经研究了增殖状态的两个主要变化：一个涉及药物制剂诱导的正常小鼠组织生长变化；另一个涉及小鼠和兔子的肿瘤生长和肿瘤浸润。(4) 我们描述了用酶法制备的18F-5-氟尿苷酸以及用酶法和直接放射化学程序制备的18F-5-氟尿苷进行的示踪实验。(5) 在用苯肼处理诱导脾脏红细胞生成增加后，小鼠脾脏中18F-5-氟尿苷脉冲后18F的摄取增加。(6) 用放线菌素D预处理后，各种小鼠组织中18F的摄取减少。这一发现与放线菌素对RNA合成的已知抑制作用一致。(7) 与正常脑组织摄取极低相比，静脉注射18F-5-氟尿苷酸或18F-5-氟尿苷的小鼠脑内齐默尔曼室管膜母细胞瘤肿瘤显示出极高的氟-18摄取。(8) 给小鼠脑内注射L1210白血病细胞悬液后，远处器官如肺、肝和脾脏受到累及。在用18F-5-氟尿苷酸脉冲标记后，这些组织的放射性显著增加，这与肿瘤细胞浸润这些组织的组织学证据一致。(9) 兔肌肉内VX2癌肿瘤显示18F的局部摄取明显高于周围正常肌肉组织。(10) 本研究最重要的临床意义在于有望通过正电子发射断层扫描在人体中追踪18F-5-氟尿苷的摄取。这将提供一种直接测量肿瘤、血液组织和其他经历快速生长变化的器官中不同体内增殖速率的方法。
