Nanomaterials and Nanofabrication Laboratories Program Announcement No. PA-08-050 (NN-Labs, LLC) Title: Near Infrared Semiconductor Nanocrystal for Imaging Guided Surgery Principal Investigator: Tiecheng Qiao Summary The incidence of brain metastasis in patients with melanoma ranges from 10% to 40% and is even higher in autopsy series. Survival rate for patients with stage IV disease is typically measured in months. Surgery is usually recommended for single brain metastases in patients with controlled or controllable systemic disease. A complete and aggressive surgical resection should be performed whenever possible followed by post-operative radiation. However, the ability to achieve complete resection (i.e., negative margin) is sometimes limited by the surgeon's ability to distinguish residual tumor from surrounding brain tissue under conventional white-light illumination. To address this technical difficulty, this Phase I project will develop a novel class of near infrared nanoparticles (NIR-NP) for imaging guide surgery (ICG) applications. Such materials are not commercially available today and will provide surgeons an ease of use surgical navigation imaging agent with precision and real time feedback, and overall, improve clinical outcome for cancer patients. We will select a tumor targeting peptide that will be attached to the surface of NIR nanoparticles. Tumor bearing mice will be used as a model to show the preferably accumulation of NIR nanoparticles on tumor site. The advantage of using a NIR nanoparticles guided resection of tumor in mice versus simple visual resection will be demonstrated. Criteria for success involve the following requirements: 1. The NIR nanoparticles must be readily dispersible biological benign solution, such as phosphate buffer saline solution (PBS), without agglomeration, 2. The NIR nanoparticles must possess good biodistribution and body clearance profile, 3. The NIR nanoparticle must meet, or exceed, clinical requirements. We will evaluate the cytotoxicity and biocompatibility of our NIR-NP through a series of in vitro assays. Ultimately, we will demonstrate the feasibility and benefit of using NIR-NP in IGS over conventional visual surgery in mice model with subcutaneously inoculated B16-BL6 melanoma. 1
Public Health Relevance: Approximately 1.5 million people in the US are diagnosed with cancer annually; and half of the 1.5 million new cancer cases diagnosed in the U.S. this year will be treated with excision surgery. One common problem associated with tumor-related surgical procedures is the difficulty for surgeons to visualize the tumor margin before the operation and to complete the excision of cancerous tissue during surgery. It is estimated that tumor reoccurrence rate could be as high as 20-30% after tumor-excision surgical procedures, and that the subsequent metastasis of unexcised cancerous growth leads to further clinical complications. The goal of this program is to develop an imaging guided surgery system using near infrared nanoparticles that would allow surgeons to maximizing tumor removal with minimal peri-tumoral damage to surrounding normal tissue. Near infrared imaging has the potential to improve the intraoperative detection of patients with malignant tumor that surgical resection is a must procedure. It is anticipated that the reduced costs and higher resolutions will permit more complete tumor resections, more accurate biopsies, and faster procedures with better patient outcomes and lower patient cost and morbidity.
Public Health Relevance Statement:Approximately 1.5 million people in the US are diagnosed with cancer annually; and half of the 1.5 million new cancer cases diagnosed in the U.S. this year will be treated with excision surgery. One common problem associated with tumor-related surgical procedures is the difficulty for surgeons to visualize the tumor margin before the operation and to complete the excision of cancerous tissue during surgery. It is estimated that tumor reoccurrence rate could be as high as 20-30% after tumor-excision surgical procedures, and that the subsequent metastasis of unexcised cancerous growth leads to further clinical complications. The goal of this program is to develop an imaging guided surgery system using near infrared nanoparticles that would allow surgeons to maximizing tumor removal with minimal peri-tumoral damage to surrounding normal tissue. Near infrared imaging has the potential to improve the intraoperative detection of patients with malignant tumor that surgical resection is a must procedure. It is anticipated that the reduced costs and higher resolutions will permit more complete tumor resections, more accurate biopsies, and faster procedures with better patient outcomes and lower patient cost and morbidity.
Project Terms:Abscission; Address; Affinity; Arg-Gly-Asp-Phe; Athymic Nude Mouse; Autopsy; Benign; Biodistribution; Biological; Biopsy; Body Tissues; Brain Metastasis; Cadmium; Cancer Patient; Cancerous; Cancers; Cd element; Classification; Clinical; Cyclic Peptides; Detection; Diagnosis; Disease; Disorder; Evaluation; Excision; Extirpation; Extracellular Matrix, Integrins; Feedback; Future; Generalized Growth; Goals; Growth; Human; Human, General; Illumination; Image; Image-Guided Surgery; In Vitro; InAs; Incidence; Integrins; Laboratories; Lighting; Lytotoxicity; Malignant Melanoma; Malignant Neoplasms; Malignant Tumor; Mammals, Mice; Man (Taxonomy); Man, Modern; Measures; Metastasis; Metastasize; Metastatic Neoplasm; Metastatic Neoplasm to the Brain; Metastatic Tumor; Metastatic Tumor to the Brain; Metastatic malignant neoplasm to brain; Mice; Mice, Athymic; Mice, Nude; Mission; Modeling; Morbidity; Morbidity - disease rate; Murine; Mus; NIH Program Announcements; Neoplasm Metastasis; Normal Tissue; Normal tissue morphology; Nude Mice; Operation; Operative Procedures; Operative Surgical Procedures; Outcome; Patients; Peptides; Phase; Phosphate Buffer; Post-Operative; Postoperative; Postoperative Period; Principal Investigator; Procedures; Program Announcement; Programs (PT); Programs [Publication Type]; Q-Dot; Quantum Dots; RGDF peptide; Radiation; Receptor Protein; Removal; Residual Tumors; Resolution; Saline; Saline Solution; Secondary Neoplasm; Secondary Tumor; Semiconductors; Series; Site; Solutions; Staging; Surface; Surgeon; Surgical; Surgical Interventions; Surgical Procedure; Surgical Removal; Survival Rate; System; System, LOINC Axis 4; Systematics; Systemic disease; Time; Tissue Growth; Tissues; Tumor Cell Migration; Tumors, Residual; Visual; arginyl-glycyl-aspartyl-phenylalanine; biocompatibility; biomaterial compatibility; brain tissue; cancer metastasis; cost; cytotoxicity; disease/disorder; experiment; experimental research; experimental study; imaging; improved; in vitro Assay; in vivo; indium arsenide; malignancy; meetings; melanoma; mouse model; nano crystal; nano fabricate; nano fabrication; nano materials; nano particle; nanocrystal; nanofabricate; nanofabrication; nanomaterials; nanoparticle; necropsy; neoplasm/cancer; novel; ontogeny; postmortem; programs; public health relevance; ray (radiation); receptor; research study; resection; residual disease; success; surgery; tumor
