Tumor imaging and therapy with novel antibody fragments, peptides and smallmolecules 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 smallmolecules 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 knowledge and 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 smallmolecules for the treatment of cancer of various types using PET/CT imaging
modality.