In Vivo Small Animal Imaging for Early Assessment of Therapeutic Efficacy of Photodynamic Therapy for Prostate Cancer
Baowei Fei1, Hesheng Wang2, Xiang Chen3
1Department of Radiology, Case Western Reserve University, University Hospitals of Cleveland, and the Case Comprehensive Cancer Center ; Department of Biomedical Engineering, Case Western Reserve University, University Hospitals of Cleveland, and the Case Comprehensive Cancer Center.
Abstract:
We are developing in vivo small animal imaging techniques that can measure early effects of photodynamic therapy (PDT) for prostate cancer. PDT is an emerging therapeutic modality that continues to show promise in the treatment of cancer. At our institution, a new second-generation photosensitizing drug, the silicon phthalocyanine Pc 4, has been developed and evaluated at the Case Comprehensive Cancer Center. In this study, we are developing magnetic resonance imaging (MRI) techniques that provide therapy monitoring and early assessment of tumor response to PDT. We generated human prostate cancer xenografts in athymic nude mice. For the imaging experiments, we used a high-field 9.4-T small animal MR scanner (Bruker Biospec). High-resolution MR images were acquired from the treated and control tumors pre- and post-PDT and 24 hr after PDT. We utilized multi-slice multi-echo (MSME) MR sequences. During imaging acquisitions, the animals were anesthetized with a continuous supply of 2% isoflurane in oxygen and were continuously monitored for respiration and temperature. After imaging experiments, we manually segmented the tumors on each image slice for quantitative image analyses. We computed three-dimensional T2 maps for the tumor regions from the MSME images. We plotted the histograms of the T2 maps for each tumor pre- and post-PDT and 24 hr after PDT. After the imaging and PDT experiments, we dissected the tumor tissues and used the histologic slides to validate the MR images. In this study, six mice with human prostate cancer tumors were imaged and treated at the Case Center for Imaging Research. The T2 values of treated tumors increased by 24 ± 14% 24 hr after the therapy. The control tumors did not demonstrate significant changes of the T2 values. Inflammation and necrosis were observed within the treated tumors 24 hour after the treatment. Preliminary results show that Pc 4-PDT is effective for the treatment of human prostate cancer in mice. The small animal MR imaging provides a useful tool to evaluate early tumor response to photodynamic therapy in mice.
Insights
Small animal magnetic resonance imaging (MRI) effectively monitors early responses to photodynamic therapy (PDT) for prostate cancer. This technique, using silicon phthalocyanine Pc 4, shows PDT
Area of Science:
- Oncology
- Medical Imaging
- Biomedical Engineering
Background:
- Photodynamic therapy (PDT) is a promising cancer treatment.
- Silicon phthalocyanine Pc 4 is a second-generation photosensitizer for PDT.
- Early monitoring of PDT efficacy is crucial for cancer treatment.
Purpose of the Study:
- To develop and evaluate in vivo small animal MRI techniques for assessing early effects of PDT on prostate cancer.
- To monitor tumor response to PDT using magnetic resonance imaging (MRI).
Main Methods:
- Human prostate cancer xenografts were established in athymic nude mice.
- High-field (9.4-T) small animal MRI with multi-slice multi-echo sequences was used.
- T2 maps and histograms were computed to analyze tumor response pre- and post-PDT.
Main Results:
- Treated tumors showed a significant increase in T2 values (24 ± 14%) 24 hours after Pc 4-PDT.
- Control tumors exhibited no significant changes in T2 values.
- Histological analysis confirmed inflammation and necrosis in treated tumors.
Conclusions:
- Small animal MRI is a valuable tool for evaluating early tumor response to PDT in preclinical models.
- Pc 4-PDT demonstrates effectiveness in treating human prostate cancer xenografts in mice.
