Cancer detection in intact animal. 23 g mouse, 300 mCi 18F-labeled PSMA, tumor on left side. Credit: SAIRP / JHU
Recent advances in materials science and in vivo molecular imaging have been the catalyst for an explosion in molecular imaging research. The use of nanodevices and nanoparticles has enabled the study of a wide variety of biological phenomena ranging from protein-protein interaction mapping to cancer detection in intact animals and man.
Key to those advances has been the emergence of functionalized nanoparticles which can be targeted specifically to molecules of biological importance such as receptors, enzymes and transporters, and have the ability to interact at the cellular level. Over the last five years there has also been a proliferation of high-resolution devices for in vivo imaging in animal models of human disease and high-throughput, such as microarray- and combinatorial-, techniques which are used to generate new targets and probes for diagnostics and therapeutics.
At the Johns Hopkins School of Medicine there are two “sister“ resources funded by the National Institutes of Health to perform molecular imaging. The In Vivo Cellular and Molecular Imaging Center (ICMIC), directed by Dr. Zaver Bhujwalla, and the Small Animal Imaging Resource Program (SAIRP) lead by Dr. Martin Pomper, both of the Department of Radiology. While the ICMIC focuses on magnetic resonance techniques to study cancer, the SAIRP tends to employ radiopharmaceutical and optical methods with a strong emphasis on chemical probe development. These two programs are complementary and closely intertwined. In addition to the chemists, physicists and biologists that comprise ICMIC and SAIRP, the molecular imaging effort at JHU thrives because of extensive collaborations throughout the university.
A fluorescent (FITC) picture showing liposomes homing to tumor metastases, indicating that they reached their tumor targets. Credit: Sgouros Lab / JHU
Recently these programs have begun to focus on applications in nanobiotechnology. For example, Dr. George Sgouros, a Professor in the Department of Radiology at JHU, has been using liposomal nanoparticles for targeted delivery of a radiation dose from bismuth-213, a radioisotope which emits alpha particles lethal to cancer. Liposomal vehicles can be decorated with a variety of targeting molecules, such as antibodies or peptides, to maximize the dose to cancer and minimize unwanted toxicity to normal tissue. By decorating a liposome with the antibody Herceptin, Dr Sgouros has it deliver its payload of bismuth-213 selectively to breast cancer cells.
Another example is Dr. Beth Laube, Professor in the Department of Pediatrics at JHU. She has used in vivo imaging to quantify mucociliary clearance in a mouse model of inflammatory disease of the lung. Dr. Laube uses radio-labeled colloid particles and planar gamma imaging to watch the particles clear the lungs over time.
Radio labeled colloid particles clearing the lung. Credit: Laube Lab / JHU
This information may be useful in testing new anti-inflammatory agents or to study lung physiology in a variety of animal models of human disease.
Other ongoing projects involve the synthesis and validation of new nanoparticle probes against prostate and a variety of other cancers. The Institute for NanoBioTechnology will soon be soliciting applications from its affiliated faculty members for the development of nanodiagnostic agents.