Quantitative radionuclide imaging study for enhanced drug delivery induced by near-infrared photoimmunotherapy

Objective: Photoimmunotherapy (PIT) is an upcoming potential cancer treatment modality. Meanwhile, due to the limited therapeutic effect of PIT alone, the combination of anticancer agents with PIT is an option to improve the therapeutic outcome. PIT causes a super-enhanced permeability and retention (SUPR) effect. The selection of drug molecule sizes that are suitable for enhanced permeability is also important for optimizing therapeutic efficacy. Thus, a method that supports to investigate the drug delivery of varying molecular weights coupled with PIT is desirable. Here, we evaluated the SUPR effect using radiolabeled drugs of varying molecular weights ( 18F-5FU, 111In-DTPA, 99mTc-HSA-D, and 111In-IgG) to determine the appropriate drug size. Methods: 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 legs. The tumor on one side was treated with PIT, and the contralateral side was not treated. The differences between tumor accumulations were quantitatively evaluated using positron emission tomography (PET) or single-photon emission computed tomography (SPECT). In this study, we used the four radionuclide imaging probes: 18F-5FU, a low-molecular-weight (148 Da) PET probe; 111In-DTPA, a low-molecular-weight (504 Da) SPECT probe, 99mT- HSA-D, a medium-molecular-weight (66492 Da) SPECT probe, and 111In-IgG, a high-molecular-weight (147111 Da) SPECT probe to quantify the SUPR effect induced by PIT. high-molecular-weight (147111 Da) SPECT probe to quantify the SUPR effect induced by PIT. Results: PIT-treated tumors showed significantly increased uptake of 18F-5FU (P < 0.001), 111In-DTPA (P < 0.05), and 99mTc-HSA-D (P < 0.02). A tendency toward increased accumulation of 111In-IgG was observed. These findings suggest that low- and medium-molecular-weight agents are promising candidates for combined PIT, and so are macromolecules; hence, administration after PIT could enhance their efficacy. Conclusion: The radionuclide imaging approach is elucidated for the PIT-mediated SUPR effect and can help in optimizing therapeutic measures by means of the feasibility of selecting a drug size and monitoring its distribution. Our findings encourage further preclinical and clinical studies to develop a combination therapy of PIT with conventional anticancer drugs.World Molecular Imaging Congres