PRECLINICAL PET IMAGING FOR TUMOUR CHARACTERIZATION: FOCUS ON HYPOXIA AND INFLAMMATION
type: CreativeWork
description: Imaging molecular techniques including PET, CT, MRI allow to detect and to monitor normal and pathological conditions non-invasively in clinic. The recent development of dedicated small animal instruments together to the availability of appropriate animal models of disease has allowed the use of these methods in preclinical research with the possibility to transfer directly the obtained results in clinic. In this thesis’s work we characterized two preclinical oncology models through the use of an animal PET instrument focusing on two processes correlated to tumour growth such as hypoxia and inflammation. Tissue hypoxia is considered as a negative prognostic factor both for answer to pharmacological and radiant therapy and for tumour progression and invasiveness. Consequently, identification and localization of hypoxic areas within the tumour have an important interest in clinical diagnostic. To this aim, BALB/c nu/nu mice were inoculated with murine cells of mammary adenocarcinoma (EMT-6) and with human cells of prostate adenocarcinoma (PC-3) and pharingeal cancer (FaDu). Animals were monitored using two hypoxic radiopharmaceutical recently developed, [18F]FAZA and [64Cu]ATSM at two different times, using PET and autoradiography. In parallel, an in vitro evaluation of specific hypoxic markers such as carbonic anhydrase IX and cupper transporters (Ctr-1 and ATP7B) was performed. In FaDu model we confirmed the same [64Cu]ATSM distribution at the two analyzed times, that is similar to that of [18F]FAZA. On the contrary, EMT-6 and PC-3 models showed a time-dependent [64Cu]ATSM uptake, with a distribution at late time (24hrs post injection) similar to that of [18F]FAZA. The different distribution of [64Cu]ATSM can be only partially explained by the different cupper pumps localization observed in vitro. Other factors such red-ox and cellular pH may influence [64Cu]ATSM uptake. PET imaging is an interesting method to identify and monitor tumour hypoxia in a non invasive wa…
abstract: Imaging molecular techniques including PET, CT, MRI allow to detect and to monitor normal and pathological conditions non-invasively in clinic. The recent development of dedicated small animal instruments together to the availability of appropriate animal models of disease has allowed the use of these methods in preclinical research with the possibility to transfer directly the obtained results in clinic. In this thesis’s work we characterized two preclinical oncology models through the use of an animal PET instrument focusing on two processes correlated to tumour growth such as hypoxia and inflammation. Tissue hypoxia is considered as a negative prognostic factor both for answer to pharmacological and radiant therapy and for tumour progression and invasiveness. Consequently, identification and localization of hypoxic areas within the tumour have an important interest in clinical diagnostic. To this aim, BALB/c nu/nu mice were inoculated with murine cells of mammary adenocarcinoma (EMT-6) and with human cells of prostate adenocarcinoma (PC-3) and pharingeal cancer (FaDu). Animals were monitored using two hypoxic radiopharmaceutical recently developed, [18F]FAZA and [64Cu]ATSM at two different times, using PET and autoradiography. In parallel, an in vitro evaluation of specific hypoxic markers such as carbonic anhydrase IX and cupper transporters (Ctr-1 and ATP7B) was performed. In FaDu model we confirmed the same [64Cu]ATSM distribution at the two analyzed times, that is similar to that of [18F]FAZA. On the contrary, EMT-6 and PC-3 models showed a time-dependent [64Cu]ATSM uptake, with a distribution at late time (24hrs post injection) similar to that of [18F]FAZA. The different distribution of [64Cu]ATSM can be only partially explained by the different cupper pumps localization observed in vitro. Other factors such red-ox and cellular pH may influence [64Cu]ATSM uptake. PET imaging is an interesting method to identify and monitor tumour hypoxia in a non invasive wa…
author: S. Valtorta
language: eng
keywords: Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
date published: 2010-12-16
date modified: 2026-07-27T20:19:17Z
provider: Università degli Studi di Milano
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Milano

PropertyValue
property ID: Handle
value: http://hdl.handle.net/2434/147852

PropertyValue
property ID: DOI
value: 10.13130/valtorta-silvia_phd2010-12-16