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Imaging marker protein design

Protein- and peptide- based chelating motifs (PBC) were previously developed by us for imaging vector distribution and transgene expression by using radionuclide imaging techniques.

We investigate several PBC motifs that transchelate technetium-99m to:

1. directly image biodistribution of non-viral gene therapy vectors

2. image gene expression using recombinant fusion proteins bearing PBC motif.

Angiogenesis Imaging

We use stady-state contrast-assisted MR imaging to measure blood volume in tumor xenografts. We use blood volume as a measure of new blood vessel formation in tumors (tumor angiogenesis). The goal of this research is to investigate early effects of novel cancer therapies directed at new blood vessel (anti-angiogenic agents).

We now established that inhibitors of VEGF receptor kinase activity induce very early changes in tumor blood volume that precede any detectable changes in tumor size.

Collaborators:

Dr. Young Kim (Massachusetts General Hospital)

Dr. Dana Hu-Lowe (Pfizer Global Research)

Dr. Christoph Bremer (Universitätsklinikum Münster)

Publications:

Kim, YR, Petrovsky A, Reichardt W, Hu-Lowe D, Kang HW, Torres D, Weissleder R, Bogdanov A Jr. Detection of early anti-angiogenic effects: in vivo changes of tumor blood volume in response to the experimental VEGF-receptor tyrosine kinase inhibitor. Cancer Res. 2005, 65: 9223-9260.

Reichardt W, Hu-Lowe D, Torres D, Weissleder R, Bogdanov A Jr. Imaging of VEGF receptor kinase inhibitor – induced anti-angiogenic effects in drug-resistant human adenocarcinoma model. Neoplasia 2005, 7:847-853.

MR image of bilateral adenocarcinomas before (A) and after (B) injection of long-circulating vascular contrast agent (PGC-Gd) and resulltant subtraction vascular image. Below: tumor before (left) and after (right) treatment with VEGF receptor inhibitor. Blood vessels are stained in blue using spepcific markers of endothelial cells

American Association for Cancer Research ©.