Abstract
With the growing interest in the use of nanoparticles (NPs) in nanomedicine, there is a crucial need for imaging and targeted therapies to determine NP distribution in the body after systemic administration, and to achieve strong accumulation in tumors with low background in other tissues. Accumulation of NPs in tumors results from different mechanisms, and appears extremely heterogeneous in mice models and rather limited in humans. Developing new tumor models in mice, with their low spontaneous NP accumulation, is thus necessary for screening imaging probes and for testing new targeting strategies. In the present work, accumulation of LipImageTM 815, a non-specific nanosized fluorescent imaging agent, was compared in subcutaneous, orthotopic and metastatic tumors of RM1 cells (murine prostate cancer cell line) by in vivo and ex vivo fluorescence imaging techniques. LipImageTM 815 mainly accumulated in liver at 24 h but also in orthotopic tumors. Limited accumulation occurred in subcutaneous tumors, and very low fluorescence was detected in metastasis. Altogether, these different tumor models in mice offered a wide range of NP accumulation levels, and a panel of in vivo models that may be useful to further challenge NP targeting properties.
Highlights
New probes for tumor imaging and local therapies are an important clinical need
Clinical developments are mainly based on new radionuclides for positron emission tomography (PET)
Determining the distribution of nanocarriers within the body following systemic administration in order to achieve high accumulation of NPs in tumors with low background in other tissues is the major challenge for nanomedicine
Summary
New probes for tumor imaging and local therapies are an important clinical need. Currently, clinical developments are mainly based on new radionuclides for positron emission tomography (PET). LipImageTM 815 NPs (50 nm) have previously been characterized for their optical and pharmacokinetic characteristics [15], and have been shown to display a long shelf life, as well as colloidal and optical stabilities, with high brightness and strong and long accumulation in subcutaneous tumors in mice [15] Injection of these NPs in immunodeficient Swiss nude mice with implanted human prostate cancer PC3 resulted in strong and long-term fluorescent labeling of the tumor [15], but data are lacking concerning NP stability. A deep tumor location is more favorable for fluorescence tomography, and FMT allowed for fluorescence detection and absolute in-depth quantification Both in vivo and ex vivo imaging methods confirmed high levels of accumulation of LipImageTM 815 in RM1 orthotopic tumors. It is not wholly representative of the clinical context, each tumor type may be useful for challenging NP properties
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