Overview
This research was designed and selected as the result of the publicly and privately funded Brain Trust meetings and deliberations of February 2004, October 2005, March 2006, and early 2007, which expanded the development of novel, breakthrough molecular imaging tools for early detection, accurate diagnosis, and minimally-invasive treatment of prostate cancer. These imaging tools are based largely on the in vivo visualization of novel molecular markers of prostate cancer previously discovered by in vitro basic research, largely in medical oncology and molecular biology. The Brain Trust stimulated the inter-disciplinary collaborations for the development of new, prostate cancer-specific molecular imaging agents.
Johns Hopkins University
Dr. Martin Pomper
Professor of Radiology and Director of the Center for Translational Molecular Imaging, Department of Radiology, Medical School
Key Accomplishment:
Developed a series of novel, prostate specific membrane antigen (PSMA)-targeting molecular imaging agents of small molecular weight within one year of funding. The preliminary results are so promising that this research was recognized as one of the most promising directions in molecular imaging at the 2008 prostate cancer conference of the National Cancer Institute, which sponsored pre-clinical studies and ultimately, human imaging. The potential of this work was also recognized with grants from the prestigious Patrick Walsh Foundation. While Dr. Pomper started research with PET imaging, AdMeTech currently supports further expansion of his research evaluating the value of PSMA-targeting agents for optical imaging and surgical interventions.
Impact on the Attraction of Talented Investigators:
Dr. Pomper, one of the international leaders of molecular imaging, was not involved with prostate imaging until he participated in AdMeTech Foundation’s Brain Trust meeting of August 2001. Since then, prostate imaging has become the major focus of this research.
Johns Hopkins University
Dr. Angelo DeMarzo
Associate Professor of Pathology, Oncology, Urology, Medical School
Key Accomplishment:
Dr. DeMarzo is a clinical pathologist, and his team successfully identified molecular markers for the AMACR gene, and demonstrated their specificity to prostate cancer. In addition, Dr. DeMarzo created a vector system for the delivery of imaging agents for the visualization of the AMACR gene in vivo. Sufficient sensitivity of this novel imaging method to detect prostate cancer was achieved and demonstrated in animal models within the first year of funding. The exciting promise of this research was recognized by an award from the National Medical Association at the 2005 Annual Meeting.
Impact on the Attraction of Talented Investigators:
Dr. DeMarzo is one of the pioneers of molecular pathology of prostate cancer who was not involved in prostate imaging until he participated in our Brain Trust meetings and public conferences starting in 1999.
Massachusetts General Hospital, Harvard Medical School
Dr. Ralph Weissleder
Professor of Radiology and Director of the Center for Systems Biology
Key Accomplishment:
Dr. Weissleder’s team pioneered an imaging method that targeted the optical visualization of the molecular marker Hepsin. Within one year of funding, Dr. Weissleder discovered that the Hepsin-specific peptide was able to bind selectively to prostate cancer. The results indicate a breakthrough potential of this imaging agent using optical imaging: The Hepsin-specific imaging agent (a peptide) was able to diagnose prostate cancer with high specificity of 100%. The high promise and success of this research is reflected in its publication by Cancer Research, one of the most prestigious academic journals.
Impact on the Attraction of Talented Investigators:
Dr. Weissleder leads one of the world-leading molecular imaging teams, and this funding made it possible for him to focus on prostate imaging.
University of Pennsylvania Medical Center
Dr. Mark Rosen
Associate Professor of Radiology (left)
Dr. Mitchell Schnall
Eugene P. Pendegrass Professor and Chairman, Department of Radiology (right)
Key Accomplishments:
This is a continuation of the original AdMeTech-funded work that focused on the development and clinical evaluation of the role of ultra-high resolution, high precision experimental 3T MRI in improving localization and staging of prostate cancer. This work accomplished the following goals:
- Successful design and phantom testing of high-field (3T) dual-loop endorectal coil prototypes;
- Successful design and in vivo use of the dual loop balloon endorectal coil at 3T; and
- Performance evaluation of 3T dual loop coil relative to standard commercial 1.5T.
These results are extremely encouraging, and suggest that the dual loop endorectal coil design is a viable means of improving image quality in high-precision, high-field prostate MRI. This work played a key role in AdMeTech’s decision to establish the International Prostate MRI Working Group, which stimulated global interest in 3T prostate MRI research.
Harvard Medical School
Dr. Ulrich von Andrian
Mallinckrodt Professor of Immunopathology
Key Accomplishments:
The goal of this research was to apply a single-cell, unique intravital microscopy technique for studies of basic biology of prostate cancer metastases and their response to treatment in order to:
- Explore the molecular and cellular mechanisms of prostate cancer cell dissemination, particularly in the bone tissue; and
- Visualize interactions of prostate cancer cells with bone and bone marrow in tumor-bearing mice.
This research team developed fluorescent dye for prostate cancer cell labeling, discovered that prostate cancer cells possess low bone marrow tropism in short-term homing experiments, and demonstrated that prostate cancer cells have a clear capacity to home on peripheral lymph nodes.
Impact on the Attraction of Talented Investigators:
Dr. Van Adrian did not consider applying this unique optical technology to prostate cancer imaging until he and his team participated in AdMeTech’s Brain Trust meetings in October 2005 and March 2006.
Brigham and Women’s Hospital, Harvard Medical School
Dr. Clare Tempany
Ferenc Jolesz Chair of Radiology Research (left)
Dr. Nathan McDannold
Research Director, Therapeutic Ultrasound Lab (right)
Key Accomplishments:
This research was conducted to test whether planning and monitoring of image-guided, minimally-invasive thermal ablation methods for the treatment of prostate cancer, such as high intensity focused ultrasound (HIFU), can be advanced by applying functional MRI techniques to assess tissue perfusion, oxygenation, and temperature before and after treatment. This research had a series of important accomplishments: Development and pilot testing of software to estimate perfusion based on dynamic contrast enhanced imaging, which was used to estimate prostate cooling by the focused ultrasound treatment device; and Implementation of motion tracking algorithms to handle prostate motion, which is one of the fundamental challenges in prostate imaging.
Impact on the Attraction of Talented Investigators:
As a result of this funding, Dr. McDannold has been recognized as a leader in the field of MRI-guided HIFU of prostate cancer.