Professor Emeritus of Biochemistry
Biochemistry - School of Medicine
Molecular Interactions Core
Research at a glance
Area(s) of Expertise
Cancer diagnostics, radiopharmaceutical imaging and therapy; cell and molecular imaging; phage display.
We have an established research program to develop radiolabeled peptides, proteins and nanoparticles as tumor specific diagnostic and therapeutic agents. Combinatorial peptide and antibody fragment libraries are being employed to identify molecules that preferentially bind tumor antigens. The tumor-avid peptides, antibody fragments and nanoparticles are subsequently engineered to bind the medically important radionuclides into their structures. Finally, the radiolabeled peptides, proteins and nanoparticles are investigated for their abilities to target tumor cells in vitro and in vivo in support of eventual clinical translation.
Radiolabeled Melanoma avid α-MSH Peptide Analogs: The goal of this project is to design radiolabeled alpha-melanocyte stimulating hormone (α-MSH) analogs for melanoma imaging and therapy. α-MSH is a small tridecapeptide hormone that binds the melanocortin-1 receptor (MC1R) over expressed on melanoma tumor cells. Cyclic α-MSH peptide analogs have been synthesized and radiolabeled with 99mTc, 111In, 64Cu and 68Ga for melanoma imaging and 188Re, 177Lu and 212Pb for melanoma therapy.
Melanoma Targeting Nanoparticles: In collaboration with Memorial Sloan Kettering and Cornell University, cyclic α-MSH analogs have been incorporated into ultrasmall (< 10 nm dia.) silica nanoparticles (C′ dots) for melanoma diagnosis, treatment and image-guided surgery. In pre-clinical melanoma animal models, the 124I-α-MSH-C′ dots were shown to imaged melanoma tumors, while in therapy studies 177Lu-DOTA-α-MSH-C′ dot treatment of melanoma bearing mice demonstrated significantly prolonged survival over control groups. Administration of α-MSH-C′ dots at high concentrations resulted in tumor cell death via a novel ferroptosis mechanism. The first generation of radiolabeled C′ dots for melanoma imaging and image-guided surgery have been translated into the clinic. Additional peptide and single chain antibody fragment (scFv) conjugated C′ dots are in the pipeline.
Tumor Binding Peptides and Antibody Fragments Selected from Bacteriophage Display Libraries: A combinatorial approach is being used to discover small peptides and single chain antibody fragments (scFvs) that bind the cancer associated Thomsen-Friedenreich (TF) glycoantigen, ErbB-2 receptor and matrix-metalloproteinase-12 (MMP-12) with high affinities and specificities from random peptide and scFv bacteriophage display libraries. Peptides that bound the TF and ErbB-2 were radiolabeled with 64Cu and used to image tumors in murine breast cancer models. Recently, MMP-12 binding scFvs were radiolabeled with 67Ga and shown to bind lung carcinomas. The MMP-12 scFvs were conjugated to the C′ dot nanoparticles, radiolabeled with 89Zr and shown to exhibit superior imaging properties to radiolabeled scFv alone.
- Ph.D. Molecular Virology, St. Louis University
- B.S. Biochemistry, University of Miami