Phase II year
2016
(last award dollars: 2017)
Phase II Amount
$1,500,000
Navidea Biopharmaceuticals has developed 99mTc-tilmanocept as a radiopharmaceutical diagnostic imaging agent targeted to the macrophage mannose receptor (CD206) to be used as an aid for lymphatic mapping in cancer surgeries. The United States Food and Drug Administration approved Navidea's new drug application (NDA) for 99mTc-Tilmanocept for use in surgeries to remove melanomas and breast tumors in May of 2013. This SBIR Fast Track application proposes a highly innovative new indication for 99mTc-tilmanocept. Based on ex vivo work with 99mTc-Tilmanocept in Kaposi's sarcoma (KS) lesions from HIV+ (AIDS) patients, Navidea, in collaboration with Drs. McGrath & Maurer of the Univ of California-San Francisco have found th a t a ll KS lesion cells express CD206. KS lesions can occur in the lungs and along the gastrointestinal tract (GI) of AIDS patients where they pose a serious and life threatening risk. Timely and accurate identification of these internal KS lesions is essential for delivery of therapies that may significantly extend the lives of AIDS patients wit KS. Current diagnostic protocols are invasive and challenged to accurately identify internal KS lesions. Our preliminary findings indicated that 99mTc-Tilmanocept could be used to more easily, less invasively and more accurately identify internal KS lesions, thereby improving both the long term outcomes and quality of care for KS patients. 99mTc- Tilmanocept has an extraordinary safety record, with no significant adverse events attributable to 99mTc- tilmanocept having been observed. The primary goal for the proposed efforts is to demonstrate that 99mTc- tilmanocept when injected intravenously can be used as a single-photon emission computed tomography (SPECT) imaging agent for visualization and identification of internal KS lesions in AIDS patients. In addition, despite the very significant progress that has been made over the last two decades in AIDS therapies, KS remains a common, serious and life threatening condition in AIDS patients worldwide. Better therapies for KS are greatly needed. If this project is successful and 99mTc-tilmanocept is demonstrated to bind specifically to cells in KS lesions, follow on studies will be performed (not part of this application) to determine if tilmanocept can be used to target delivery of therapeutics to KS lesions. Targeted delivery of therapeutics may greatly improve their efficacies providing a very significant additional benefit t KS patients. This Fast Track SBIR application proposes preclinical animal studies examining the safety of intravenous injection of 99mTc-tilmanocept (part 1) followed by a clinical study providing the initial evaluation of the safety and efficacy of SPECT imaging studies with 99mTc-tilmanocept to identify internal KS lesions in human patients (part 2).
Public Health Relevance Statement: Public Health Relevance: This project, if successful, has the potential to dramatically improve life expectancies, quality of care and quality of life for patients suffering from Kaposi's sarcoma (KS). Due to the unexpected observation that KS tumor cells abundantly express the macrophage mannose receptor (CD206), we propose to test the feasibility that Navidea Biopharmaceutical's FDA approved CD206 binding diagnostic radiopharmaceutical, 99mTC-tilmanocept, can be used to identify internal and difficult to find KS lesions. If successful, follw on studies will determine if tilmanocept can be used to target delivery of therapeutics directly to KS tumor cells.
NIH Spending Category: Cancer; Clinical Research; Diagnostic Radiology; Emerging Infectious Diseases; HIV/AIDS; Infectious Diseases; Orphan Drug; Patient Safety; Rare Diseases
Project Terms: Acquired Immunodeficiency Syndrome; Address; Adverse event; Affinity; Animals; base; Binding; Biological Products; Biopsy; Bronchoscopy; California; cancer surgery; Cells; chemotherapy; Chest; Clinical Data; Clinical Protocols; Clinical Research; Collaborations; Contracts; Cutaneous; design; Detection; Development; Diagnosis; Diagnostic; Diagnostic Imaging; Drainage procedure; Endoscopy; Evaluation; experience; FDA approved; Gastrointestinal tract structure; Goals; Grant; Health; Herpesviridae; high risk; Highly Active Antiretroviral Therapy; Histologic; HIV; Human; Image; Imagery; imaging agent; Imaging technology; improved; innovation; Institutional Review Boards; Intervention; intravenous administration; intravenous injection; Kaposi Sarcoma; Laboratory Study; Lesion; Life; Life Expectancy; Lung; lymph nodes; Lymphatic; macrophage; Mammary Neoplasms; mannose receptor; Maps; Marketing; Mediating; melanoma; mortality; neoplastic cell; Nodal; novel therapeutics; Operative Surgical Procedures; Outcome; Patients; performance site; Phase; Phase III Clinical Trials; pre-clinical; protocol development; Protocols documentation; Quality of Care; Quality of life; Radiopharmaceuticals; receptor; Recruitment Activity; response; Risk; Safety; San Francisco; Sensitivity and Specificity; Sentinel Lymph Node; Sentinel Lymph Node Mapping; Site; Small Business Innovation Research Grant; Solid Neoplasm; Specificity; targeted delivery; targeted treatment; Technology; Testing; Therapeutic; Tomography, Emission-Computed, Single-Photon; Training; tumor; United States Food and Drug Administration; Virus Diseases; Wit; Work; X-Ray Computed Tomography
