Improved Tumor Rediotherapy by MORF Pretargeting

通过 MORF 预靶向改进肿瘤放射治疗

基本信息

批准号：
7258505
负责人：
DONALD J HNATOWICH
金额：
$ 24.08万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-03-01 至 2012-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7258505
关键词：
90Y Acids Acute Adenine Affinity Agreement Americas Amides Amines Anhydrides Animal Rights Animals Anti-CEA Antibody Antibodies Area Area Under Curve Attention Avidin Base Sequence Behavior Beta Particle Binding Binding Sites Biodistribution Biological Assay Biotin Bispecific Antibodies Bladder Blood Blood Circulation Boston Buffers CC49 antibody Cancer Patient Carbodiimides Caring Cell surface Cells Characteristics Charge Chelating Agents Chemical Structure Cities Clinical Collimator Complement Complementary DNA Condition Contralateral Control Animal Control Groups Controlled Study Count Coupling Cultured Cells Cytosine DNA Daily Data Data Set Dendrimers Deposition Detection Development Development, Other Dextrans Diagnosis Diagnostic Diffusion Dimensions Discipline of Nuclear Medicine Dissociation Dorsal Dose Drug Kinetics Electrons Equilibrium Exhibits Exposure to Fluorescence Fluorescence Resonance Energy Transfer Frequencies Funding Furuncles Future Gamma Cameras Goals Growth Half-Life Hand Harvest Health Sciences Heart Heating High Pressure Liquid Chromatography Hour Human Image Immunoglobulin G Implant In Situ In Vitro Incubated Individual Infection Inflammation Injection of therapeutic agent Institution Investigation Ion-Exchange Chromatography Procedure Ions Iowa Kidney Kidney Neoplasms Knowledge Label Laboratories Left Length Lesion Literature Liver Liver neoplasms Lucite Lung Lysine Mass Spectrum Analysis Measurement Measures Melanocytic nevus Metabolism Methods Metric Microspheres Modality Modeling Mole the mammal Molecular Molecular Target Molecular Weight Monoclonal Antibody CC49 Mus Muscle N,N-diisopropylethylamine Nature Neoplasm Antibodies Normal Horse Serum Normal tissue morphology Nude Mice Numbers Oklahoma Optics Organ Organ Size Paper Patients Penetration Pentetic Acid Peptide Nucleic Acids Phase Phosphate Buffer Photons Pliability Polyethylene Glycols Polylysine Polymers Polystyrenes Positioning Attribute Preparation Principal Investigator Printing Procedures Process Property Protein Binding Publications Purines Purpose Pyrimidine Pyrimidines Pyrrolidinones Radiation Radiation therapy Radio Radioactivity Radioimmunoconjugate Radioisotopes Radiolabeled Radiopharmaceuticals Rate Reagent Recombinant DNA Relative (related person)Reporting Research Research Design Research Personnel Rest Ribosomal DNA Right-On Risk Rotation S-acetylmercaptoacetyltriglycine N-hydroxysuccinimide Saline Salivary Scheme Series Serum Side Signal Transduction Simulate Site Skin Societies Solubility Solutions Source Spleen Standards of Weights and Measures Stomach Streptavidin Structure Students Surface Surface Plasmon Resonance System Tartrates Technetium Tc 99m Mertiatide Temperature Testing Text Therapeutic Therapeutic Effect Thick Thigh structure Thinking Thymine Thyroid Gland Time Tissues Tracer Transient Global Amnesia Tumor Antibodies Tumor Tissue Tumor Weights Uncertainty United States National Institutes of Health Universities Urine Variant Vertebral column Water Weight Width absorption acetone hydrazone antibody conjugate antibody engineering aqueous base bone cancer diagnosis carboxylate chemical synthesis concept cost day density design dextran disuccinimidyl glutarate disuccinimidyl suberate dosage experience falls fluorescence imaging fluorophore immunoreactivity improved in vivo inhibitor/antagonist interest maleic acid malignant breast neoplasm man microautoradiography molecular modeling mouse model multidisciplinary neoplastic cell novel strategies optical imaging perrhenate phosphodiester phosphorothioate posters pre-clinical prevent programs purine radiotracer residence sensor simulation size success tartrate tool trend tumor tumor growth uptake vinyl ether whole body imaging

项目摘要

DESCRIPTION (provided by applicant): Pretargeting of tumor is becoming a mature, reasonably well understood and successful imaging modality. The advantage of pretargeting is usually not in higher absolute tumor accumulation but in higher tumor/normal tissue ratios achieved rapidly. This laboratory is exploring several novel approaches to pretargeting, each having in common the use of oligomers in place of either streptavidin/biotin or bispecific antibodies. In the course of investigating oligomers for "conventional" pretargeting, it became apparent that these interesting molecules have many useful properties for this application. In addition to conventional pretargeting, these studies have led to the development of three new subfields of investigation that we call "amplification pretargeting", "affinity enhancement pretargeting with oligomers" and, most recently, "optical pretargeting". Because of the novelty of using oligomers in radiopharmaceutical design, and in particular MORFs for pretargeting applications, we were required to develop methods of labeling MORFs with 99mTc and 188Re, develop new methods of conjugating antibodies and polymers with MORFs, develop methods of synthesizing bivalent MORFs with different spacings and, most recently, explore cellular accumulations of fluorophore conjugated MORFs. In addition, it was necessary to calibrate our tumor mouse model to better understand its properties with respect to pretargeting so that tumor and normal tissue accumulations could be accurately predicted with changes in variables. These and other developments have been successfully accomplished as documented in our publications in print, in press, submitted and in preparation. We intend to continue these investigations of MORF pretargeting by emphasizing our conventional preclinical pretargeting radiotherapy studies with 188Re-MORFs into (with supplemental funding) tracer studies in patients; 2) improving upon pretargeting by continuing our MORF amplification and MORF affinity enhancement pretargeting of tumors. We will also continue our MORF pretargeting studies with optical detection. Our multidisciplinary UMMS team consisting of chemists, radiation physicists and a molecular biologist has experience in each phase of this investigation. The proposed studies will now build upon our past results to achieve our goal of greatly improving upon conventional molecular targeting of tumor for improved cancer diagnosis and, especially, radiotherapy.