Susan Evans-Axelsson

Tumor imaging and therapy with novel antibody fragments, peptides and small-molecules using frontline nuclear medicine approaches and imaging modalities

Susan Evans-Axelsson

Abstract

Target-specific molecular imaging and therapy of tumors provides a noninvasive means of determining the extent and biological features of the cancer, while also monitoring therapeutic responses over time. The imaging modality, positron emission tomography (PET) used in conjunction with computed tomography (CT), is currently one of the leading imaging modalities used for the assessment and monitoring of many types of cancers. In the Ahmanson Translational Imaging Division at the University of California, Los Angeles, my objective is to assess the in vivo targeting ability and therapeutic response of novel antibody fragments, peptides and small-molecules to tumors of various cancers types using frontline nuclear medicine approaches and imaging modalities.

My original thesis work was completed at Lund University in the Department of Clinical Sciences in Malmö, Sweden and was based on preclinical multimodality imaging of prostate cancer using radiolabeled monoclonal antibodies. My goal now is to expand my knowledgeand transfer my skills to work within the field of Molecular Imaging, particularly within Nuclear Medicine. In my capacities as a PhD student and subsequent Laboratory Researcher, my role was largely based on establishing animal models of prostate cancer (both solid tumor and metastatic models), administering labeled antibodies or novel drugs, collecting samples and analyzing the results. The first two years of my PhD work was based on ex vivo analysis of the samples, i.e. multi-isotope digital autoradiography (DAR), gamma-count measurements and immunohistochemistry. Once the Lund Bioimaging Center (LBIC) was established, I began to follow antibody biodistribution and tumor targeting in live animals, mainly with single-photon emission computed tomography (SPECT)/CT but also with PET/CT.

I will use what I have learned to further develop my research skills and gain more independence as a postdoc in Dr. Czernin’s lab. I will move from my thesis work in Clinical Sciences to learn the ins and outs of Nuclear Medicine, especially in PET imaging, where I will detect, monitor and treat many different tumor types using novel antibody fragments, peptides and small-molecules. I will use my expertise in establishing metastatic and solid tumors animal models of prostate cancer to develop animal models of various other cancer types, for example, gliomas and neuroendocrine cancers.

UCLA is the number 1 world leading PET center. And as the location where the first clinical PET system was developed and put into service for scanning patients it is the perfect setting for me to conduct my postdoc studies focusing on imaging cancer with the PET imaging modality. The Ahmanson translational imaging division’s preclinical imaging laboratory at UCLA has a substantially large array of frontline molecular imaging modalities and resources that I will have at my disposal for my preclinical imaging studies. The imaging lab where I will conduct my research is equipped with a Genisys PET (Sofie Biosciences), a bench-top pre-clinical scanner with combined x-ray, camera for surface optical images and a mouse atlas, all used for anatomical references. The lab is also equipped with the Inveon microPET (Siemens) and microCT small animal CT system (microCAT II, Siemens Preclinical Solutions).

The projects for which I will be involved have the potential to contribute to relevant breakthroughs in cancer diagnosis and treatment using novel peptides, antibody fragments and small-molecules with innovative nuclear medicine techniques and state-of-the art translational imaging instrumentation.

Purpose and objectives

Primary objectives

Objective #1. … to assess the tumor targeting and biodistribution of novel radiolabeled peptides and antibody fragments for imaging cancer in small animal models of various tumor types using positron emission tomography together with computed tomography (PET/CT). I will also compare the peptides and antibody fragments performance against established tracers currently used in the clinic, for example the metabolic tracer 18FDG or the proliferation tracer 18F-choline.

Objective #2. … to conjugate therapeutic radionuclides to the most promising peptides and antibody fragments for targeted therapy of various cancers.

Secondary objective

Objective #3. … to assess the in vivo ability of a number of novel small-molecules for the treatment of cancer of various types using PET/CT imaging modality.