Abstract
Increasingly, in vivo imaging holds a strategic position in bio-pharmaceutical innovation. We will present the implementation of an integrated multimodal imaging setup enabling the assessment of multiple, complementary parameters. The system allows the fusion of information provided by: Near infrared fluorescent biomarkers, bioluminescence (for tumor proliferation status), Photoacoustic and Ultrasound imaging. We will study representative applications to the development of a smart prodrug, delivering a highly cytotoxic chemotherapeutic agent to cancer tumors. The results realized the ability of this embedded, multimodality imaging platform to firstly detect bioluminescent and fluorescent signals, and secondly, record ultrasound and photoacoustic data from the same animal. This study demonstrated that the prodrug was effective in three different models of hypoxia in human cancers compared to the parental cytotoxic agent and the vehicle groups. Monitoring by photoacoustic imaging during the treatments revealed that the prodrug exhibits an intrinsic capability to prevent the progression of tumor hypoxia. It is essential for onco-pharmacology studies to precisely document the hypoxic status of tumors both before and during the time course of treatments. This approach opens new perspectives for exploitation of preclinical mouse models of cancer, especially when considering associations between hypoxia, neoangiogenesis and antitumor activity.
Highlights
In vivo imaging holds a strategic position in bio-pharmaceutical innovation
The major differences that were expected relied on the ability of the photoacoustic imaging (PA) system to detect these different fluorochromes
The PA absorption peak measured by a Spectro-Acquisitions show slightly shifted peaks in the far red direction as compared to the intrinsic characteristics of the dyes alone
Summary
In vivo imaging holds a strategic position in bio-pharmaceutical innovation. Regarding the use of both CT and radioactive techniques, the dosimetry resulting from repeated irradiations received by animals (including tumors) have to be considered when imaging sessions are performed longitudinally Molecular imaging modalities such as bioluminescence (BLI), near infrared fluorescence (NIRF), ultrasound imaging (US) and recently photoacoustic imaging (PA) are becoming increasingly useful imaging modalities for preclinical research. Their use provides relevant information regarding tumor kinetics and require no particular radioprotection environment compared to nuclear techniques. This combination has never been described before This prototype platform consists of a new-generation, low-cost CMOS camera (Fig. 1E) for BLI and NIRF, inserted inside the commercial enclosure of the VEVO LAZR system (US and PA acquisitions). Biophotonics techniques are cheap, with affordable consumables (e.g. targeted probes, luciferin, antibodies, as compared to isotopes) and a very low maintainance cost
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