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Quantitative Radionuclide Imaging Analysis of Enhanced Drug Delivery Induced by Photoimmunotherapy

Authors :
Winn Aung
Atsushi B. Tsuji
Aya Sugyo
Masayuki Fujinaga
Ming-Rong Zhang
Tatsuya Higashi
Source :
International Journal of Molecular Sciences, Vol 22, Iss 15, p 8316 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

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 (18F-5FU, 111In-DTPA, 99mTc-HSA-D, and 111In-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 18F-5FU (p < 0.001) and 99mTc-HSA-D (p < 0.001). A tendency toward increased accumulation of 111In-DTPA and 111In-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.

Details

Language :
English
ISSN :
22158316, 14220067, and 16616596
Volume :
22
Issue :
15
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.8cc8f8f4550a446b81f572b4beb280d8
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms22158316