Cancer has been a deadly disease threatening humans. Traditional treatment methods such as chemotherapy with non-specific targeting may cause... Show moreCancer has been a deadly disease threatening humans. Traditional treatment methods such as chemotherapy with non-specific targeting may cause severe side effects to normal cells and tissues. Novel and better methods for treatment and imaging of cancer has been eagerly sought. We wanted to develop new small molecule inhibitors and antibody drug conjugates for targeted cancer therapy and imaging. Theranostic conjugates combining therapeutic entity and imaging agent are useful in treatment and diagnosis of cancer. We designed a theranostic conjugate containing iron chelating anti-tumor agent and optical imaging probe. Novel iron chelator CAB-NE3TA displayed significant anti-proliferation activity against several cancer cell lines and was conjugated to targeting antibody panitumumab (PAN). The therapeutic conjugate exhibited excellent anti-tumor efficacy and targeting ability to EGFR overexpressed on cancer cells such as skin cancer (A431). The theranostic conjugate CAB-NE3TA-PAN loaded with a near IR fluorescent dye provided promising anti-tumor efficacy and optical imaging in tumor-bearing mice. Tetrahydroisoquinoline (THIQ) analogues were synthesized and evaluated for cytotoxicity against different cancer cell lines. Our in vitro studies showed that the THIQ analogues exhibited anti-proliferative activities against multiple cancer cell lines. Cytotoxicity study revealed that anti-tumor activity of THIQ analogues are structure-dependent. Binding affinity between THIQ analogues and a potential target Tdp1 was determined. Positron emission tomography (PET) has been used in diagnosis of cancer. In this study, small molecules and chelators with potential donor groups were evaluated systematically for complexation with 89Zr for PET imaging. New ligands with different donors were evaluated for radiolabeling efficiency and complex stability with 89Zr. The theranostic conjugate (CAB-NE3TA-PAN-IR800) and small molecule THIQs and 89Zr-chelators showed encouraging results for potential applications in for therapy and imaging of cancer. Show less
