Abstract
Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of antibodies for targeting tumors with the toxicity induced by photon absorbers after irradiation with NIR light. The purpose of this study was to determine if MR imaging can detect changes in the MR properties of tumor within several hours of NIR-PIT. A431 cells were injected subcutaneously in the right and left dorsi of 12 mice. Six days later, the mice were injected with a photon absorber, IR700, conjugated to panitumumab, an antibody targeting epidermal growth factor receptor. One day later, only right sided tumor was exposed to NIR light (treated tumor). MRI was performed 1 day before and 1-2 hours after NIR-PIT using gadofosveset for six mice and gadopentetate dimeglumine for another six mice. T2 relaxation times, the apparent diffusion coefficient (ADC) for the following combinations of b-values: 0-1000, 200-1000 and 500-1000 s/mm2 and enhancement indices were compared before and after NIR-PIT using a two-sided paired t-test. For treated tumors, T2 relaxation time increased after NIR-PIT (p < 0.01) and all three ADC values decreased after NIR-PIT (p < 0.01). Moreover, the enhancement area under the curve (AUC) using gadofosveset increased after NIR-PIT (p = 0.02). In conclusion, prolongation of T2, reductions in ADC and increased enhancement using gadofosveset are seen within 2 hours of NIR-PIT treatment of tumors. Thus, MRI can be a useful imaging biomarker for detecting early therapeutic changes after NIR-PIT.
Highlights
Near infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that employs a targeted monoclonal antibody conjugated to a photon absorber, IRDye700DX (IR700, silica-phthalocyanine dye) [1]
Non-treated tumors exhibited a decline in apparent diffusion coefficient (ADC) values for one but not all b value pairings
This study demonstrates that NIR-PIT induces rapid changes in the MR properties of tissues that can be readily measured using standard MR pulse sequences available on practically all Magnetic resonance imaging (MRI) units
Summary
Near infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that employs a targeted monoclonal antibody conjugated to a photon absorber, IRDye700DX (IR700, silica-phthalocyanine dye) [1]. The first-in-human phase I trial of NIR-PIT in patients with inoperable head and neck cancer targeting epidermal growth factor receptor was approved by the US FDA, and is underway as of June 2015 (https://clinicaltrials.gov/ct2/ show/NCT02422979) In this trial, a patient is injected with an antibodyphoton absorber conjugate (APC) that binds to target molecules on the cell membrane of the tumor. SUPR effects induced by NIR-PIT have been reported to allow 5-15 fold increases in accumulation of the liposomal anti-cancer agent (DaunoXome®) resulting www.impactjournals.com/oncotarget in more effective therapy than either NIR-PIT or liposomal anti-cancer agent alone These changes occur within 20 min of NIR light exposure, yet gross tumor size and shape do not change for several days after NIR-PIT
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