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Multimodality imaging of tumor response to doxil
11. Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Purpose:
Early assessment of tumor responses to chemotherapy could enhance treatment outcomes by ensuring that, from the beginning, treatments meet the individualized needs of patients. In this study, we applied multiple modality molecular imaging techniques to pre-clinical monitoring of early tumor responses to Doxil, focusing on imaging of apoptosis.
Methods:
Mice bearing UM-SCC-22B human head and neck squamous cancer tumors received either PBS or 1 to 2 doses of Doxil® (doxorubicin HCl liposome injection) (10 mg/kg/dose). Bioluminescence signals from an apoptosis-responsive reporter gene were captured for apoptosis evaluation. Tumor metabolism and proliferation were assessed by( 18)F-FDG and 3'-(18)F-fluoro-3'-deoxythymidine ((18)F-FLT) positron emission tomography. Diffusion-weighted magnetic resonance imaging (DW-MRI) was performed to calculate averaged apparent diffusion coefficients (ADCs) for the whole tumor volume. After imaging, tumor samples were collected for histological evaluation, including terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), anti-CD31, and Ki-67 immunostaining.
Results:
Two doses of Doxil significantly inhibited tumor growth. Bioluminescence imaging (BLI) indicated apoptosis of tumor cells after just 1 dose of Doxil treatment, before apparent tumor shrinkage. (18)F-FDG and (18)F-FLT PET imaging identified decreased tumor metabolism and proliferation at later time points than those at which BLI indicated apoptosis. MRI measurements of ADC altered in response to Doxil, but only after tumors were treated with 2 doses. Decreased tumor proliferation and increased apoptotic cells were confirmed by changes of Ki-67 index and apoptotic ratio.
Conclusion:
Our study of tumor responses to different doses of Doxil demonstrated that it is essential to combine apoptosis imaging strategies with imaging of other critical biological or pathological pathways, such as metabolism and proliferation, to improve clinical decision making in apoptosis-related diseases and interventions.
Insights
Early molecular imaging detected apoptosis after one Doxil dose, preceding tumor shrinkage. Combining apoptosis, metabolism, and proliferation imaging is crucial for effective cancer treatment decisions.
Area of Science:
- Oncology
- Molecular Imaging
- Cancer Biology
Background:
- Early assessment of chemotherapy response is vital for personalized cancer treatment.
- Monitoring tumor response to Doxil (doxorubicin HCl liposome injection) can optimize patient outcomes.
- Apoptosis imaging offers a sensitive marker for early therapeutic effects.
Purpose of the Study:
- To evaluate early tumor responses to Doxil using multi-modality molecular imaging.
- To focus on imaging apoptosis as a primary indicator of Doxil treatment efficacy.
- To correlate imaging findings with histological assessments of tumor response.
Main Methods:
- Mice with human head and neck squamous cancer xenografts received Doxil or PBS.
- Apoptosis was assessed using bioluminescence imaging (BLI) of a reporter gene.
- (18)F-FDG and (18)F-FLT PET, DW-MRI, and histological analyses (TUNEL, Ki-67, CD31) were performed.
Main Results:
- One dose of Doxil induced apoptosis detected by BLI before significant tumor shrinkage.
- Decreased tumor metabolism and proliferation were observed later via PET imaging.
- Apparent diffusion coefficients (ADCs) from MRI changed after two Doxil doses; histological analysis confirmed increased apoptosis and reduced proliferation.
Conclusions:
- Apoptosis imaging with BLI provides an early indicator of Doxil's effect on tumors.
- Integrating apoptosis imaging with assessments of metabolism and proliferation enhances clinical decision-making.
- Multi-modal imaging strategies are essential for comprehensive evaluation of chemotherapy response in cancer.
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