Targeted Pb-212 therapy in preclinical animal tests has shown a cure in groups receiving the highest dose of this therapy. Scaling the dose that was most efficacious in animal studies to people would bring the human dose required from 50 to 100 mCi. This application will research an approach that would provide a generator system that would support these requirements. The proposed work will investigate a generator system that would trap the short-lived radon-220 and isolate and test Pb-212/Bi-212 obtained. The Ra-224 and Th-228 emanation generators would be scaled up to the multi-millicurie level and assessment of their performance over time, including overall yield and verification of zero breakthrough of Ra-224 or Th-228. Finally, the suitability of the product Pb-212/Bi-212 to label anti- melanoma peptide moieties and the improved specific activity of Pb-212 expected of an emanation generator will be tested.
Public Health Relevance: A cure for melanoma, a deadly form of skin cancer, has been demonstrated in preclinical animal tests using Pb-212 labeled peptide. As this therapy moves to the clinic the current generator system needs to be improved to accommodate higher dose levels that are anticipated to be administered.
Public Health Relevance Statement: Project Narrative A cure for melanoma, a deadly form of skin cancer, has been demonstrated in preclinical animal tests using Pb-212 labeled peptide. As this therapy moves to the clinic the current generator system needs to be improved to accommodate higher dose levels that are anticipated to be administered.
Project Terms: 2-Propanol; 224Ra; Achievement; Achievement Attainment; Affinity; Air; Air Pressure; Alpha Particle Radiation; Alpha Particles; Animal Cancer Model; Animal Model; Animal Models and Related Studies; Animal Testing; AnimalModel; Animals; Antibodies; Applications Grants; Astatine; Ba element; Barium; Bathing; Baths; Bi element; Binding; Binding (Molecular Function); Bismuth; Boxing; Cancer Patient; Cancer Radiotherapy; Cancers; Carbon Dioxide Snow; Charcoal; Chemicals; Classification; Clinic; Clinical; Clinical Trials; Clinical Trials, Unspecified; Coupled; Cultured Cells; Daughter; Definitive Radiation Therapy; Deposit; Deposition; Development; Disease; Disorder; Dose; Drug Kinetics; Dry Ice; EBRT; Exhibits; External Beam RT; External Beam Radiation Therapy; External Radiation; Gamma Rays; Gases; Gel; Grant Proposals; Grants, Applications; Hour; Human; Human, General; Ion Exchange; Isopropanol; Isopropyl Alcohol; Label; Length; Life; Linear Energy Transfer; MC1 Receptor; Malignant Melanoma; Malignant Neoplasms; Malignant Skin Neoplasm; Malignant Tumor; Malignant Tumor of the Skin; Mammals, Mice; Man (Taxonomy); Man, Modern; Measures; Mechanics; Melanocortin Receptor 1; Melanocyte Melanocortin Receptor; Melanoma and Non-Melanoma Skin Cancer; Metastasis; Metastasize; Metastatic Neoplasm; Metastatic Tumor; Methods; Mice; Modeling; Molecular Interaction; Murine; Mus; Neoplasm Metastasis; Neoplasms; Octadecanoates; Parents; Patients; Peptides; Performance; Pharmacokinetics; Phase; Physical condensation; Primary Neoplasm; Primary Tumor; Product Labeling; Production; Publishing; Ra-224; Radiation; Radiation therapy; Radiation, Alpha; Radiation, Gamma; Radioactive Isotopes; Radioactivity; Radioimmunoconjugate; Radioisotope Generators; Radioisotopes; Radiolabeled Antibodies; Radionuclide Generators; Radionuclides; Radiotherapeutics; Radiotherapy; Radium-224; Radon; Receptor Protein; Receptor, Melanocortin, Type 1; Research; Resistance; Rn element; Rubbing Alcohol; Sampling; Secondary Neoplasm; Secondary Tumor; Skin Cancer; Skin Cancer, Including Melanoma; Spectroscopy; Spectrum Analyses; Spectrum Analysis; Stearates; System; System, LOINC Axis 4; Systematics; Temperature; Testing; Therapeutic Effect; Time; Translations; Tumor Cell; Tumor Cell Migration; Tumors; Universities; Variant; Variation; Vent; Vial; Vial device; Work; abstracting; base; cancer metastasis; chemotherapy; clinical applicability; clinical application; clinical investigation; condensation; design; designing; disease/disorder; external-beam radiation; improved; in vivo; irradiation; malignancy; melanoma; model organism; neoplasia; neoplasm/cancer; neoplastic cell; neoplastic growth; particle; pre-clinical; preclinical; preclinical study; radium, isotope of mass 224; ray (radiation); receptor; resistant; scale up; seal; success; thorium X; tumor; tungstate; uptake
