Jamal Zweit - Overview
Understanding the molecular mechanisms underlying the development of anti-cancer therapies requires direct in vivo investigation of the pharmacokinetic (PK) profile which can be directly related to measurements of specific pharmacodynamic (PD) endpoints. The aim is to provide clearer and more direct evidence of potential molecular targeting mechanisms and anti-tumour efficacy. This is facilitated by molecular targeting and imaging research, based on positron-emitting tracers and Positron Emission Tomography (PET), to investigate specific biochemical pathways involved in tumour progression and targeted therapy of cancer. Our programme focuses on in vivo PET imaging based on the characterisation of targeting molecules and PET probes in relation to:
- drug delivery and pharmacokinetics
- endothelium targeting and anti-angiogenic therapy and
- molecular imaging of apoptosis.
A major focus of the programme is in the molecular imaging of angiogenesis and apoptosis as specific molecular targets for novel anti-cancer therapy. With the aim of characterising biological response to novel anti-angiogenic therapy, we have characterised the PK profile of 124I-labelled anti-VEGF molecule, which has enabled us to conduct the first PET imaging study of an anti-angiogenic therapy. With a view of developing PET tracers for new drug targets, we are exploiting the apoptotic pathways annexin V/ phosphatidyl serine binding and caspase 3 inhibition to target PET radioligand probes which will enable the quantitative imaging of drug-induced apoptosis in an in vivo model.
The research work within the group is interactive and is facilitated by strong research and clinical links with other groups and departments at the Paterson Institute, the Christie Hospital, the University of Manchester and UMIST and the pharmaceutical industry.
