Naslov
Development of Non-Natural Nucleoside Analogues for Monitoring Gene Therapy with Positron Emission Tomography (PET)

Autori
Raić-Malić, Silvana

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
XXI. Hrvatski skup kemičara i kemijskih inženjera / Novak, Predrag - Trogir : Hrvatsko društvo kemijskih inženjera i tehnologa (HDKI), 2009, 32-32

ISBN
978-953-6894-38-3

Skup
XXI. Hrvatski skup kemičara i kemijskih inženjera

Mjesto i datum
Trogir, Hrvatska, 19.04.2009. - 22.04.2009

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
C-6 Substituted Thymine Derivatives; 18F-Radiolabeling; Positron Emission Tomography

Sažetak
Positron emission tomography (PET) has become a powerful scientific and clinical tool for probing biochemical processes in the human body. The clinical application of PET using molecules labelled with positron emitting radioisotopes has proven to be vital in the evaluation and diagnosis of diseases such as tumors, neurological disorders, cardiac diseases. Some purine and pyrimidine nucleoside analogues labelled with radionuclides 18F and 124I were evaluated for monitoring clinical gene therapy using PET. In order to develop new PET-tracers with greater sensitivity, specificity and low bystander cytotoxic effects, a new series of C-6 alkylated pyrimidines have been synthesized. Newly prepared compounds exhibited no toxicity and showed better in vitro binding affinities for herpes simplex virus type 1 thymidine kinase (HSV 1-TK) than prodrugs acyclovir and ganciclovir. Compounds that are phosphorylated by HSV 1-TK to their corresponding monophosphates and metabolically trapped in transfected cells represent new candidates for in vivo imaging of HSV 1-TK enzyme activity. The crystal structure of C-6 substituted pyrimidines in complex with HSV 1-TK have been solved. The syntheses and biological evaluations of unlabelled non-natural nucleoside analogues, as well as their 18F radiolabelling using nucleophilic substitution reaction on appropriate leaving groups will be presented.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA