Detection of myeloma in skeleton of mice by whole-body optical fluorescence imaging
Babatunde O Oyajobi1, Steve Muñoz, Rami Kakonen
1Department of Cellular and Structural Biology MSC 7762, University of Texas Health Science Center at San Antonio, Texas 78229-3900, USA. oyajobi@uthscsa.edu
Abstract:
Development of new therapies for myeloma has been hindered by the lack of suitable preclinical animal models of the disease in which widespread tumor foci in the skeleton can be detected reliably. Traditional means of detecting skeletal tumor infiltration such as histopathology are cumbersome and labor-intensive and do not allow temporal monitoring of tumor progression or regression in response to therapy. To resolve this problem, we modified the Radl 5TGM1 model of myeloma bone disease such that fluorescent myeloma tumors can be optically imaged in situ. Here, we show that murine myeloma 5TGM1 tumor cells, engineered to express enhanced green fluorescent protein (eGFP; 5TGM1-eGFP cells), can be imaged in a temporal fashion using a fluorescence illuminator and a charge-coupled device camera in skeletons of live C57BL/KaLwRij mice. High-resolution, whole-body images of tumor-bearing mice revealed that myeloma cells homed almost exclusively to the skeleton, with multiple focal tumor foci in the axial skeleton, consistent with myeloma tumor distribution in humans. Finally, the tested antitumor treatment effect of Velcade (bortezomib), a proteasome inhibitor used clinically in myeloma, was readily detected by GFP imaging, suggesting the power of the technique in combination with the Radl 5TGM1-eGFP model for rapid preclinical assessment and sensitive monitoring of novel and potential therapeutics. Whole-body GFP imaging is practical, convenient, inexpensive, and rapid, and these advantages should enable a high throughput when evaluating in vivo efficacy of new potential antimyeloma therapeutics and assessing response to treatment.
Insights
Developing new myeloma therapies requires better animal models. This study created a fluorescent myeloma model for in vivo imaging, enabling rapid assessment of new treatments and tracking tumor progression.
Area of Science:
- Oncology
- Biomedical Imaging
- Translational Research
Background:
- Preclinical models for multiple myeloma are limited in reliably detecting skeletal tumor burden.
- Traditional methods for monitoring myeloma bone disease are labor-intensive and prevent temporal analysis.
Purpose of the Study:
- To develop a novel preclinical model for multiple myeloma that allows for in vivo optical imaging of skeletal tumor foci.
- To establish a method for temporal monitoring of tumor progression and response to therapy in a myeloma bone disease model.
Main Methods:
- Engineered murine myeloma 5TGM1 cells to express enhanced green fluorescent protein (eGFP), creating 5TGM1-eGFP cells.
- Utilized fluorescence imaging with a charge-coupled device camera to visualize myeloma tumors in the skeletons of live mice.
- Administered Velcade (bortezomib) to assess the model's ability to detect therapeutic effects.
Main Results:
- Myeloma cells (5TGM1-eGFP) selectively homed to the skeleton, forming focal lesions in the axial skeleton, mirroring human disease.
- Whole-body GFP imaging enabled reliable, temporal monitoring of tumor growth and regression in response to Velcade treatment.
- The imaging technique proved practical, convenient, inexpensive, and rapid for evaluating therapeutic efficacy.
Conclusions:
- The 5TGM1-eGFP model provides a powerful tool for preclinical assessment of novel antimyeloma therapeutics.
- GFP imaging facilitates sensitive and high-throughput monitoring of therapeutic response in vivo.
- This approach accelerates the evaluation of potential myeloma treatments.
