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Real-time monitoring of microdistribution of antibody-photon absorber conjugates during photoimmunotherapy in vivo.
- Source :
-
Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2017 Aug 28; Vol. 260, pp. 154-163. Date of Electronic Publication: 2017 Jun 08. - Publication Year :
- 2017
-
Abstract
- Photoimmunotherapy (PIT) is an emerging low side effect cancer therapy based on a monoclonal antibody (mAb) conjugated with a near-infrared (NIR) phthalocyanine dye IRDye 700DX. IR700 is fluorescent, can be used as an imaging agent, and also is phototoxic. It induces rapid cell death after exposure to NIR light. PIT induces highly selective cancer cell death, while leaving most of tumor blood vessels unharmed, leading to an effect called super-enhanced permeability and retention (SUPR). SUPR significantly improves the effectiveness of the anticancer drug. Currently, the therapeutic effects of PIT are monitored using the IR700 fluorescent signal based on macroscopic fluorescence reflectance imagery. This technique, however, lacks the resolution and depth information to reveal the intratumor heterogeneity of mAb-IR700 distribution. We applied a minimally invasive two-channel fluorescence fiber imaging system by combining the traditional fluorescence imaging microscope with two imaging fiber bundles (~0.85mm). This method monitored mAb-IR700 distribution and therapeutic effects during PIT at different intratumor locations (e.g., tumor surface vs. deep tumor) in situ and in real time simultaneously. This enabled evaluation of the therapeutic effects in vivo and treatment regimens. The average IR700 fluorescence intensity recovery after PIT to the tumor surface is 91.50%, while it is 100.63% in deep tumors. To verify the results, two-photon microscopy combined with a microprism was also used to record the mAb-IR700 distribution and fluorescence intensity of green fluorescent protein (GFP) at different tumor depths during PIT. After PIT treatment, there was significantly higher IR700 fluorescence recovery in deep tumor than in the tumor surface. This phenomenon can be explained by increased vascular permeability immediately after NIR-PIT. Fluorescence intensity of GFP at the tumor surface decreased significantly more compared to that of deep tumor and in controls (no PIT).<br /> (Copyright © 2017. Published by Elsevier B.V.)
- Subjects :
- Animals
Antibodies, Monoclonal chemistry
Antibodies, Monoclonal pharmacokinetics
Carbocyanines chemistry
Carbocyanines pharmacokinetics
Cell Line, Tumor
Female
Fluorescent Dyes chemistry
Fluorescent Dyes pharmacokinetics
Green Fluorescent Proteins
Immunoglobulin G immunology
Infrared Rays
Mice, Nude
Neoplasms metabolism
Neoplasms pathology
Organophosphorus Compounds chemistry
Organophosphorus Compounds pharmacokinetics
Panitumumab
Tumor Burden
Antibodies, Monoclonal administration & dosage
Carbocyanines administration & dosage
Fluorescent Dyes administration & dosage
Immunotherapy
Neoplasms therapy
Organophosphorus Compounds administration & dosage
Phototherapy
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4995
- Volume :
- 260
- Database :
- MEDLINE
- Journal :
- Journal of controlled release : official journal of the Controlled Release Society
- Publication Type :
- Academic Journal
- Accession number :
- 28601576
- Full Text :
- https://doi.org/10.1016/j.jconrel.2017.06.004