Preclinical Oncology Studies Using Multimodal Optical Imaging

Todd A Sasser1, Andrew Van Praagh1 and Jens Waldeck2

1Bruker Molecular Imaging, 44 Manning Rd, Billerica, MA 01821 US

2Bruker BioSpin MRI GmbH, Rudolf-Plank-Str. 23 76275 Ettlingen DE

While in vivo, multimodal optical imaging is now commonly used in a range of research disciplines including infection, inflammation, and metabolic diseases, it was first extensively applied in preclinical studies of oncology. Optical imaging is particularly well suited for cost efficient, sensitive, and high throughput in vivo tumor detection, monitoring and follow-up. Bioluminescence imaging (BLI) and fluorescence imaging (FLI) have been widely used to detect and quantify tumor burden in subcutaneous (SQ) and orthotopic tumor models. Longitudinal in vivo optical imaging has facilitated studies in tumor biology and cancer therapeutics. Additionally, in vivo FLI is used extensively to detect molecular markers (MMs) of tumor biology as well as in studies of probe development. Direct radionuclide imaging (DRI) has been particularly useful in evaluating candidate small-molecule oncology tracers and in discovering throughput biodistribution and in vivo targeting of novel therapeutic compounds.

Multimodal Oncology

C-myc-BCL2 leukemia mouse and FL metastatic tumor imaging. Tumor cells engineered for fluorescent protein mCherry expression to facilitate in vivo FLI. Images courtesy of Dr. Sebastian Baeumer, Medical Clinic A, Molecular Hematology & Oncology, University Hospital Muenster, Germany and Dr. Christiane Geyer: IZKF/ TRIC/IKR Muenster, University Hospital Muenster, Germany (Unpublished).

MultimodalOncology 01

Multimodal BLI/X-ray prostate tumor imaging. (Left) The X-ray contrast agent Visipaque™ (GE Healthcare) was administered prior to multimodal imaging providing enhanced kidney and bladder radiographic contrast. Middle) Prostate tumor cells transduced with firefly luciferase were imaged after administering luciferin via tail vein injection. (Right) BL image is registered with the X-ray for anatomical context. Images provided courtesy of Professor Bob Handa, Arizona State University, USA (Unpublished).

The Bruker In-Vivo Multispectral FX PRO and In-Vivo Xtreme systems provide multimodal BLI, FLI, DRI, CLI (Cherenkov luminescense imaging), and X-ray imaging capabilities. These systems have been utilized in numerous preclinical oncology studies for in vivo tumor detection/monitoring and for the detection of cancer molecular markers. This review presents a set of representative preclinical oncology studies performed using the Bruker In-Vivo optical imaging systems. The selected studies used BL (e.g. firefly luciferase), FL (e.g. GFP, RFP, and NIR fluorophores), and/or DRI (e.g. 99mTc and 125I) reporters, and have advanced developments in tumor reporter systems and probes, cancer therapeutics, and have provided insights in to basic tumor biology. The note may also serve as a general primer to optical imaging methods and reporters used in preclinical oncology. 

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