Development and use of technetium-99, rhenium-186 and rhenium-188-labeled liposomes for nuclear imaging and radionuclide therapy

There has been a great deal of interest in using in vivo targeted radionuclide therapy. The current challenge of targeted radionuclide therapy is finding excellent radiolabeled agents, which will give a high and uniform radiation dose to tumors but much lower doses to normal tissues.; Liposomes have been investigated widely as universal carriers for the delivery of drugs, genes and antigens. Many nuclear imaging studies and several recent theoretical articles have demonstrated the promising potential of radiolabeled liposomes for targeted radionuclide therapy.; A novel, practical and convenient liposome labeling method using 99mTc, 186Re and 188Re, which have promising characteristics for nuclear imaging or radionuclide therapy, has been developed. 99mTc/186Re-“SNS/S” complexes were studied to label liposomes following two trapping mechanisms: (1) ligand exchange with pre-encapsulated glutathione (GSH), cysteine or other thiol group containing chemicals; (2) the 99mTc/186Re-“SNS/S” complexes contain amine groups, which can be trapped following pH gradient or ammonium gradient mechanism. High labeling efficiency and good labeling stability were achieved as characterized by in vitro and normal rat distribution studies. This labeling method can also be used to label liposomes that encapsulate therapeutic agents with the potential of combination therapy using both radionuclides and chemotherapeutic agents within the same liposome formulation.; Initial studies with breast cancer-bearing rats after intratumoral administration have been performed. After an intratumoral injection of 99mTc-(NH ₄)₂SO₄ liposomes labeled with 99mTc-BMEDA, prolonged tumor retention and very high tumor-to-normal tissue ratios of 99mTc-activity were observed. These results have demonstrated the potential use of 186Re/188Re-liposomes with an intratumoral administration technique to treat tumors.; These dissertation results are very encouraging and have stimulated future studies of using 186Re/188Re-liposomes for targeted radionuclide therapy.