This Core will enable key insights into the pharmacokinetics and biodistribution of the humanized form of our Annexin A1 targeting antibody (hAnnA1) by providing 89Zr-hAnnA1 for imaging studies in both preclinical and a first-in-human clinical trial. The goal of the Core D Radiochemistry Core is to radiolabel antibodies for use in Projects 1 and 3. Core D will also conduct the pilot imaging study with 89Zr-hAnnA1 that is prepared by the Core under cGMP conditions. Imaging with hAnnA1-based targeting is promising due to high target affinity and specificity which leads to reduced off target effects. When hAnnA1 is conjugated to radionuclides for imaging, new radiopharmaceuticals can be developed which are complementary to more conventional imaging modalities. The Core will enable the caveolae pumping system to be evaluated for its ability to deliver precisely antibodies labeled with radionuclides directly into solid tumors and metastastic lesions. Core D will produce radiotracers essential to the aims in Projects 1 and 3, and will be instrumental in the development of novel precision delivered radiopharmaceuticals to image and treat metastatic disease in humans.
CORE D NARRATIVE Our goal is to overcome the vasculature barrier and deliver imaging and therapeutic agents directly into solid tumors where they can be most effective. By maximizing precision delivery of radio- and chemo-therapies, current treatments can be replaced by those that are more effective and less toxic. The development of new radiopharmaceuticals optimized for precision delivery into solid tumors will synergistically complement more conventional imaging modalities or chemotherapeutics to improve treatment for patients suffering from metastatic disease.