Studies in the mouse of the pharmacology of 5-iododeoxyuridine, an analogue of thymidine

Prusoff, William H.; Jaffe, Julian J.; Günther, Helge L.

doi:10.1016/0006-2952(60)90027-7

Cited by 81 publications

(19 citation statements)

References 12 publications

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“…This could be attributed to the relatively high affinity of ITdU to TK1. Another factor that affects incorporation of radiolabeled thymidine analogues into DNA is the C-N glycoside cleavage reaction catalyzed by thymidine phosphorylase and preventing their use in DNA synthesis (49,50). The thymidine phosphorylase assay confirmed that the substitution of the 4 ¶-oxygen by sulfur in the ITdU molecule increased the stability of the glycosidic bond (17).…”

Section: Discussionmentioning

confidence: 99%

Preferential Tumor Targeting and Selective Tumor Cell Cytotoxicity of 5-[131/125I]Iodo-4′-Thio-2′-Deoxyuridine

Morgenroth¹,

Deisenhofer²,

Glatting³

et al. 2008

Clinical Cancer Research

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Section: Discussionmentioning

confidence: 99%

Preferential Tumor Targeting and Selective Tumor Cell Cytotoxicity of 5-[131/125I]Iodo-4′-Thio-2′-Deoxyuridine

Morgenroth¹,

Deisenhofer²,

Glatting³

et al. 2008

Clinical Cancer Research

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“…Both drugs During the last 10 years 5-fluoro-2'-deoxyuridine (5-were used because they inhibit the activity of the en-FUDR), also known as floxuridine, has been used in zyme thymidylate synthetase, thereby blocking DNA the treatment of acute childhood leukemia [16], neuroreplication [7,26,27,32]. blastoma, Hodgkin's disease [35], and a variety of More recently 5-FUDR and 5-IUDR have been used other tumors such as breast and rectal carcinoma [9, as antiviral agents.…”

Section: Introductionmentioning

confidence: 99%

Floxuridine and Its Influence on Postnatal Cerebellar Development

1972

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ExtractHuman infants with eytomegalovirus and herpes simplex are presently treated with floxuridine (5-FUDR), a DNA synthesis blocking agent. Since in the cerebellum of the newborn infant neuron formation continues for some time after birth, the question arises whether 5-FUDR might cause permanent damage to the cerebellum. In our experiment 21 2-day-old mice were treated by three injections of 5-FUDR (50 mg/kg body weight per injection), and particular attention was given to damage and subsequent repair of the external granular layer, the site of postnatal neuron formation. In the anterior lobes of the vermis most proliferating external granular cells died and repair was minimal. Purkinje cells were dispersed and few if any basket cells were formed. In the posterior lobes, including the uvula, considerable repair of the external granular layer was noted. The final cerebellar architecture, however, was never normal, and heterotopic granule cell nests were found in the molecular layer. In the intermediary lobes repair occurred, but Purkinje cells were found throughout the granular layer. Since the human cerebellum at birth is characterized by a thick external granular layer, it is not impossible that 5-FUDR may also cause disturbances in the human cerebellar architecture and function.

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“…HSE is usually caused by HSV-1, and the clinical symptoms are nonspecific (17). Despite many attempts to devise noninvasive diagnostic tests, brain biopsy is still the only definitive means of diagnosing HSE (22 (19).…”

mentioning

confidence: 99%

Pharmacokinetics and metabolism of E-5-(2-[131I]iodovinyl)-2'-deoxyuridine in dogs

Samuel¹,

Gill²,

Iwashina³

et al. 1986

Antimicrob Agents Chemother

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E-5-(2-lodovinyl)-2'-deoxyuridine (IVdU) is a potent inhibitor of herpes simplex virus type 1 replication in vitro. The selective antiviral activity of IVdU is due to pireferential phosphorylation by the herpes simplex virus type 1-encoded thymidine kinase. This selective sequesteration provided the rationale for the development of radioiodinated IVdU as a potential radiopharmaceutical compound for use in noninvasive diagnosis of herpes simplex virus encephalitis. We studied the pharimacokinetics and the in vivo metabolism of [131 ]IVdU in dogs.The radioactive components in plasma were characterized and quantitated by radio high-pressure liquid chromatography. During incubation with dog blood, [13'IJIVdU was metabolized to the corresponding base (E)-5-(2-iodovinyl)uracil. '311-labeled (E)-5-(2-iodovinyl)uracil accounted for 73% of the total radioactivity present in plasma after 2 h of incubation, suggesting that phosphorilysis of the nucleoside is the major degradation pathway of IVdU in blood. The in vivo studies showed that there was an initial rapid clearance of the tracer from blood, followvd by a second very slow clearance phase, Evaluation of the renal excretion of the radiotracer showed that only 8% of the injected dose was excreted by kidneys over an 8-h period. IVdU was rapidly metabolized to three radioactive compounds. Two of these metabQlites, the base (E)-5-(2-iodovinyl)uracil and iodide, were characterized. The radioactivity associated with these metabolites was responsible for the slow clearance phase. Our results suggest that the development of [1311]IVdU as a radiopharmaceutical compound will require measures to prevent its rapid degradation in vivo.

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Studies in the mouse of the pharmacology of 5-iododeoxyuridine, an analogue of thymidine

Cited by 81 publications

References 12 publications

Preferential Tumor Targeting and Selective Tumor Cell Cytotoxicity of 5-[131/125I]Iodo-4′-Thio-2′-Deoxyuridine

Preferential Tumor Targeting and Selective Tumor Cell Cytotoxicity of 5-[131/125I]Iodo-4′-Thio-2′-Deoxyuridine

Floxuridine and Its Influence on Postnatal Cerebellar Development

Pharmacokinetics and metabolism of E-5-(2-[131I]iodovinyl)-2'-deoxyuridine in dogs

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