The ultimate goal of this SBIR proposal is to develop novel molecular imaging markers for monitoring tumor early response and efficacy to anti-angiogenic treatment regimens. Anti-angiogenic therapy represents an exciting advance in the management of cancer. Targeting of the vasculature has been shown to benefit patients with several types of malignancies. Hundreds of molecules with anti-angiogenic activity in preclinical models have been reported, and many of them have entered clinical testing in oncology. It is predicted that Avastin will be the top one drug in 2014 with a projected $8.9 billion in sales. Although many patients benefit from anti-angiogenic therapies, it is often by achieving stability of their disease and only half of patients are benefit from Avastin therapy due to lack of response to the treatment. Furthermore, there is no Avastin-response specific biomarker-based technologies to monitor anti-angiogenic therapies in the product development pipeline. Thus, development of noninvasive biomarkers of disease response and relapse is a crucial objective to aid in the management of patients. Rapid assessment of cancer response to a therapeutic regimen can determine efficacy early in the course of treatment. Early evaluation of cancer response to a therapeutic regimen can help adjust the efficacious treatment scheme, terminate ineffective treatments, minimizing unnecessary toxicity and expenditure. Recently, we applied phage display strategy and identified peptides that can selectively bind to tumors that respond to anti-angiogenic therapies. We identified a 12-mer peptide from phage display library that binds specifically to anti-angiogenic drug Avastin responsive tumors but not non-responsive or untreated tumors. This peptide was termed as Avastin- responsive peptide (AVRP). In this Phase I SBIR proposal, we will extend these efforts and further explore and develop clinically relevant AVRP specific probes for PET imaging monitoring tumor early response and efficacy to anti-tumor angiogenesis treatments. We will evaluate the ability of AVRP peptide to quantitatively measure tumor response to Avastin treatment in various tumor types and treatment regimens. We will also study the mechanism of AVRP action by identifying the target protein(s) of AVRP. Furthermore we will test a number of other therapies to determine whether suitably labeled AVRP peptide can be used as a universal probe to image cancer treatment efficacy in general. We will commercialize the product after we accomplish the SBIR project. The innovation in this proposal is to explore a novel strategy for developing efficient targeted imaging probes for monitoring tumor early response and efficacy to anti-angiogenic treatment. The success of this proposal will provide exciting promise to accelerate and reduce the cost of drug development, stratify patient populations, assess the treatment efficacy, and minimize the duration of treatment with ineffective regimens in cancer patients.
Public Health Relevance: We will develop the clinically translatable novel molecular imaging probes for monitoring tumor early response and efficacy to anti-angiogenic treatment regimens. Rapid assessment of cancer response to a therapeutic regimen can determine efficacy early in the course of treatment. We anticipate that the new tracers will provide early evaluation of cancer response to a therapeutic regimen that can help accelerate the drug development, adjust the efficacious treatment scheme, reduce the healthcare cost, eventually leading to personalized cancer therapy, treatment monitoring, and dose optimization.
Thesaurus Terms: Affinity;Angiogenesis Antagonists;Angiogenesis Blockers;Angiogenesis Inhibitors;Angiogenetic Antagonists;Angiogenetic Inhibitors;Angiogenic Antagonists;Angiogenic Inhibitors;Angiostatic Agents;Anti-Angiogenesis;Anti-Angiogenetic Agents;Anti-Angiogenic Agents;Anti-Angiogenic Drugs;Antiangiogenesis;Antiangiogenesis Agents;Antiangiogenic Agents;Avastin;Binding;Binding (Molecular Function);Cancer Patient;Cancer Treatment;Cancers;Clinical;Clinical Evaluation;Clinical Oncology;Clinical Protocols;Clinical Testing;Computer Models;Computer Simulation;Computer Based Simulation;Computerized Models;Development;Disease;Disorder;Docking;Dose;Drug Delivery;Drug Delivery Systems;Drug Kinetics;Drug Targeting;Drugs;Evaluation;Expenditure;Far-Western Blotting;Goals;Health Care Costs;Health Costs;Healthcare Costs;Image;Imaging Procedures;Imaging Technics;Imaging Techniques;Industry;Loinc Axis 2 Property;Label;Malignant Neoplasm Therapy;Malignant Neoplasm Treatment;Malignant Neoplasms;Malignant Tumor;Mathematical Model Simulation;Mathematical Models And Simulations;Measures;Medication;Metabolic;Modeling;Molecular Interaction;Molecular Target;Monitor;Neovascularization Inhibitors;Oncology Cancer;Pet;Pet Scan;Pet Imaging;Petscan;Pett;Patients;Peptide Phage Display Library;Peptides;Phage Display;Pharmaceutic Preparations;Pharmaceutical Preparations;Pharmaceutics;Pharmacokinetics;Pharmacy (Field);Phase;Phase I Study;Positron Emission Tomography Medical Imaging;Positron Emission Tomography Scan;Positron-Emission Tomography;Pre-Clinical Model;Preclinical Models;Preparation;Property;Protein Binding;Proteins;Proteomics;Rad.-Pet;Radiation Therapy;Radiolabeled;Radiotherapeutics;Radiotherapy;Regimen;Relapse;Reporting;Sbir;Sbirs (R43/44);Sales;Schedule;Scheme;Sensitivity And Specificity;Small Business Innovation Research;Small Business Innovation Research Grant;Solid;Technology;Testing;Therapeutic;Toxic Effect;Toxicities;Tracer;Translations;Treatment Efficacy;Treatment Period;Treatment Protocols;Treatment Regimen;Treatment Schedule;Tumor Angiogenesis;Tumor Volume;West-Western Blotting;Angiogenesis;Antiangiogenesis Therapy;Antiangiogenic;Anticancer Research;Anticancer Therapy;Base;Biomarker;Cancer Research;Cancer Therapy;Cellular Targeting;Clinical Applicability;Clinical Application;Clinical Relevance;Clinical Test;Clinically Relevant;Computational Modeling;Computational Models;Computational Simulation;Computer Based Models;Computerized Modeling;Computerized Simulation;Cost;Developmental;Disease/Disorder;Drug Development;Drug Discovery;Drug/Agent;Experiment;Experimental Research;Experimental Study;Gene Product;Imaging;Imaging Probe;Improved;In Silico;In Vivo;Innovate;Innovation;Innovative;Insight;Intervention Efficacy;Laser Capture Microdissection;Malignancy;Molecular Imaging;Multimodality;Neoplasm/Cancer;New Approaches;Novel;Novel Approaches;Novel Strategies;Novel Strategy;Oncology;Patient Population;Phase 1 Study;Phase 2 Study;Phase Ii Study;Pre-Clinical Research;Preclinical Research;Preclinical Toxicity;Product Development;Programs;Radiolabel;Radiotracer;Research Clinical Testing;Research Study;Response;Safety Study;Success;Therapeutic Efficacy;Therapeutically Effective;Therapy Efficacy;Treatment Days;Treatment Duration;Tumor;Uptake;Virtual Simulation
