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РЖ ВИНИТИ 34 (BI36) 96.04-04А4.368

No-carrier-added (NCA) 1-('бета'-D-arabinofuranosyl)-5(E)-(2-radioiodovinyl) uracil (Ivarau) probes for the detection of Herpes simplex virus (HSV)-specified thymidine kinase (TK) in vivo and in vitro [Text] : [Abstr.] 40th Annu. Meet. Soc. Nucl. Med., Toronto, June 8-11, 1993 / H. Dougan [et al.] // J. Nucl. Med. - 1993. - Vol. 34, N 5 Suppl. - P236 . - ISSN 0161-5505
Перевод заглавия: 1-('бета'-D-арабинофуранозил)-5(E)-(2-радиойодвинил)урацил (IVaraU) - метка без носителя для определения тимидинкиназы (ТК), специфичной для вируса Herpes simplex (HSV)
Аннотация: A vinyl tributyltin precursor for IVaraU was prepared: treatment of the known compound 1-(2,3,5-tri-O-toloyl-'бета'-D-arabino furanosyl)-5-iodouracil (1) with E-1,2-bis(tributylstannyl)ethene and catalytic (Ph[3]P)[2]PdCl[2] in 1,2-dichloroethane gave the protected vinyl tributyltin nucleoside (2) (46%); treatment of 2 with NaOMe/MeOH gave (E)-5-[2-tributylstannylvinyl]-arabinosyluridine (3) (72%). Reaction of 3 with [I-123]NaI (10 mCi) or [I-125]NaI (2 mCi) and chloramine T in methanol, gave NCA [I-123] or [I-125]IVaraU in up to 98% labeling yield (2.5 min); IVaraU was further purified by reversed phase HPLC (acetonitrile/H[2]O (85/15)) in 88% recovered yield. Accumulation of NCA [I-125]IVaraU in HSV-infected tissue culture was both time and inoculum dependent, using six serial 10-fold dilutions from 1.0 moi to 0.00001 moi of HSV-1 (strain 294.1) adsorbed onto human embryonic lung fibroblasts at 5000 * g for 30 min at 37'ГРАДУС'C with 2.8 * 10{6} cpm of [I-125]IVaraU. HSV infections of 1.0, 0.1, 0.01, 0.001, 0.0001, and 0.00001 moi were detectable at 2, 4, 8, 10, 14, and 16 h, respectively, defining positive as uptake:background 1.75. TK-dependent uptake of [I-125]IVaraU was demonstrated using TK{+} and TK{-} HSV strains. [I-125]IVaraU was also studied in a mouse HSV encephalitis model using lip-inoculated strain AJ mice 7 days post-infection. After tail vein injection of [I-125]IVaraU, HSV-infected:uninfected brain uptake ratios at 1, 2, 24, and 48 h were 1.2, 6.5, 15.8, and 36.2, respectively. IVaraU is a novel and highly specific probe for HSV TK activity in vitro and in vivo. США, The Univ. of British Columbia, Vancouver, BC

ГРНТИ	34.49.37

ВИНИТИ 341.49.37.13
Рубрики: РАДИОФАРМПРЕПАРАТЫ
ЙОД-125
УРАЦИЛ * L-('БЕТА'-D-АРАБИНОФУРАНОЗИЛ)-5(E)-(2-РАДИОЙОДВИНИЛ
СИНТЕЗ
ВИРУС ГЕРПЕСА ОБЫКНОВЕННОГО
ТИМИДИНКИНАЗА
ВИЗУАЛИЗАЦИЯ

Доп.точки доступа:
Dougan, H.; Rennie, B.A.; Wanklin, R.J.; Lyster, D.M.; Vo, C.; Sacks, S.L.

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