| Autor: |
Aung W; Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum and Radiological Science and Technology (QST-iQMS), Inage, Chiba 263-8555, Japan., Tsuji AB; Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum and Radiological Science and Technology (QST-iQMS), Inage, Chiba 263-8555, Japan., Sugyo A; Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum and Radiological Science and Technology (QST-iQMS), Inage, Chiba 263-8555, Japan., Fujinaga M; Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum and Radiological Science and Technology (QST-iQMS), Inage, Chiba 263-8555, Japan., Zhang MR; Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum and Radiological Science and Technology (QST-iQMS), Inage, Chiba 263-8555, Japan., Higashi T; Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum and Radiological Science and Technology (QST-iQMS), Inage, Chiba 263-8555, Japan. |
| Abstrakt: |
Photoimmunotherapy (PIT) is an upcoming potential cancer treatment modality, the effect of which is improved in combination with chemotherapy. PIT causes a super-enhanced permeability and retention (SUPR) effect. Here, we quantitatively evaluated the SUPR effect using radiolabeled drugs of varying molecular weights ( 18 F-5FU, 111 In-DTPA, 99m Tc-HSA-D, and 111 In-IgG) to determine the appropriate drug size. PIT was conducted with an indocyanine green-labeled anti-HER2 antibody and an 808 nm laser irradiation. Mice were subcutaneously inoculated with HER2-positive cells in both hindlimbs. The tumor on one side was treated with PIT, and the contralateral side was not treated. The differences between tumor accumulations were evaluated using positron emission tomography or single-photon emission computed tomography. Imaging studies found increased tumor accumulation of agents after PIT. PIT-treated tumors showed significantly increased uptake of 18 F-5FU ( p < 0.001) and 99m Tc-HSA-D ( p < 0.001). A tendency toward increased accumulation of 111 In-DTPA and 111 In-IgG was observed. These findings suggest that some low- and medium-molecular-weight agents are promising candidates for combined PIT, as are macromolecules; hence, administration after PIT could enhance their efficacy. Our findings encourage further preclinical and clinical studies to develop a combination therapy of PIT with conventional anticancer drugs. |
