Description:
MULTI-FUNCTIONAL LINKING AGENT FOR IMAGING AND THERAPY
Imaging technologies are uniquely positioned to enhance how localized and metastatic tumors are treated. In cases where surgery is indicated, a novel class of imaging agents which combine radioactive of fluorescent tags can be used to improve tumor visualization in real-time. When cancer has spread throughout the body, a cytotoxic compound can be combined with radioactive label to develop a “theranostic” method to see and treat disease. Tumor-specificity is critical to the success of these approaches and investigators at The University of Texas Health Science Center at Houston have developed a multimodality chelator (MMC) scaffold that allows enhancement of clinically established targeting agents to improve how surgery and therapy are performed.
Technology Overview
An interdisciplinary team of investigators in the Institute of Molecular Medicine at The University of Texas Health Science Center at Houston have developed a multimodality chelation (MMC) scaffold that is capable of assembling various targeting agents, fluorophores, and therapeutic agents on a single moiety. Their focus is to add additional imaging and/or therapeutic capabilities to clinically validated imaging agents, and the MMC scaffold allows them to accomplish this while retaining key imaging characteristics of the targeting agent (i.e., affinity, rapid elimination, low non-specific signal). For example, the MMC can be used to link a cancer-targeting peptide with a near-infrared agent so that a specific tumor type could be visualized pre-operatively using a PET/CT scan and intraoperatively using near-infrared imaging systems. Additionally, the modularity of the MMC scaffold enables conversion of a conventional imaging agent into a “theranostic” analog by mounting a therapeutic payload, thus providing a new therapeutic option for patients and a built-in patient selection strategy.
Potential Applications
• Prep-operative PET imaging for surgical planning and fluorescence-guided surgery to improve patient outcomes with a single agent
• Validation of intraoperative agents through dual-labeling with the MMC scaffold can facilitate translational studies
• Targeted drug delivery to tumors with highly potent cytotoxics which cannot be used alone
• Potential to provide new therapeutic options to patients which would not otherwise be indicated
Technology Advantages
• Modular, various payloads can be attached to MMC;
• Retains bioactivity of targeting agent;
• Suitable for incorporation into solid-phase synthesis;
• Compatible with various radionuclides; and
• Compatible with all relevant bioconjugation techniques
Intellectual Property Status:
• Issued US Patent No. 10,441,607; pending US continuation application
• Portfolio available for licensing.
Stage of Development
The investigators have developed multimodality imaging agents and “theranostics” from a standard MMC and have tested these in vivo. Additional in vivo studies are ongoing.
Associated Publication
Multimodal chelation platform for near- infrared fluorescence/nuclear imaging; PMID 23214723.
Image description. (Top) Ex vivo staining of fresh human NET cryosections using Ga-MMC(IR800)-TOC. SSTR2 IHC shows high expression in tumor and low expression in non-tumor tissue (a, b). Membrane staining of Ga-MMC(IR800)-TOC in the tumor area co-localized with SSTR2 and binding in normal tissue was drastically lower (c). (Bottom) PET (a) and in vivo NIRF imaging of 68Ga-MMC(IR800)-TOC in HCT116-SSTR2 xenografts showing increasing tumor uptake from 3 h (b) to 24 h (c) p.i. Fluorescence signal from Ga-MMC(IR800)-TOC from ex vivo NIRF imaging (d). Arrow indicates tumor.
About the Investigator
Dr. Ali Azhdarinia’s laboratory is at the interface of chemistry and biology and is focused on developing molecules for the visualization and treatment of disease. Using novel chemistry platforms, they have the ability to produce molecules with multiple labels and thus, multiple applications. The apply fundamental expertise in chemistry, imaging, and drug characterization to develop new classes of molecular imaging agents and focus on translation of discoveries and technologies into the clinic to improve human health.