Imaging Prostate Cancer with 99mTc-trofolastat
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Visualizing Disease
Medical imaging is a non-invasive means of obtaining a picture of the internal structure and workings of the human body. Currently, the most common methods of visualizing disease provide images of anatomy and include Magnetic Resonance Imaging (MRI), fluoroscopy, Computed Axial Tomography (CAT scan or CT scan), X-ray, and ultrasound. These methods have limited utility in patients at early stages of disease when gross anatomical changes are not yet evident, in patients who have undergone surgical procedures to treat their disease and anatomy is difficult to assess, or in patients who have systemic disease where the precise locations are unknown.
Molecular imaging differs from anatomical medical imaging in that radioactive drugs are used to detect disease through visualization of physiology and biochemistry, enabling physicians better insight into the disease process. This is markedly different from anatomical imaging and has opened up additional applications for detecting the presence, location and quantity of disease throughout the body. Such images provide vital information related to the diagnosis and extent of disease, prognosis and, ultimately, therapeutic management options.
How it Works
Molecular imaging radiopharmaceuticals are targeted radioactive substances that facilitate the visualization of subtle changes in biochemical and biological processes associated with disease progression. The expression of distinct proteins by diseased cells offers the opportunity to diagnose and characterize disease by probing the biochemical composition and phenotypic identity of the diseased tissue.
Molecular Insight uses radiolabeled small molecules that bind to specific receptors, enzymes and proteins in the body that are altered during the evolution of disease. After administration to a patient, these molecules circulate in the blood until they find their intended target. The bound radiopharmaceutical remains at the site of disease, while the rest of the agent clears rapidly from the body. The radioactive portion of the molecule serves as a beacon so that an image may be obtained depicting the disease location and concentration using commonly available nuclear medicine cameras, known as single-photon emission computerized tomography (SPECT) or positron emission tomography (PET) cameras, found in most hospitals throughout the world. Physicians can then use this information to determine the presence and the extent of disease in a patient, resulting in optimal patient and disease management.
99mTc-TROFOLASTAT
Trofolastat is Molecular Insight’s molecular imaging radiopharmaceutical product candidate under development for the detection of metastatic prostate cancer. This compound targets the extracellular domain of prostate specific membrane antigen (PSMA), a protein amplified on the surface of >95% of prostate cancer cells and a validated target for the detection of primary and metastatic prostate cancer. Trofolastat is labeled with technetium-99m, an isotope that is widely available, relatively inexpensive, facilitates ease of preparation, and has optimal diagnostic gamma ray energy for nuclear medicine imaging applications.
In patients with metastatic prostate cancer, 99mTc-trofolastat rapidly localizes to lesions in lymph nodes and bone on whole-body imaging as early as 1 hour post injection with the following results: SPECT/CT images demonstrate excellent lesion contrast target-to-background ratios; enlarged and sub-centimeter lymph nodes are clearly visualized as is the diseased prostate gland; good correlation is seen with bone scans in most subjects although, in general, more lesions are visualized with 99mTc-trofolastat than with bone scan.
Molecular Insight’s Investigational New Drug application for 99mTc-trofolastat was allowed in the second quarter of 2012. The Company initiated a multi-center international Phase 2 clinical trial in high risk prostate cancer patients undergoing prostatectomy.