Talk Summary:
Conventional imaging evaluates therapeutic response primarily through changes in tumor size or morphology. However, these anatomical changes may take weeks or months to become apparent, delaying determination of whether a treatment is effective. Earlier assessment could help avoid prolonged exposure to ineffective and potentially toxic therapies.

This talk will first provide a brief overview of molecular imaging approaches developed to evaluate therapeutic response. These methods assess treatment-induced changes in processes such as tumor metabolism, cellular proliferation, and immune activity. By detecting biological responses that may precede measurable anatomical changes, molecular imaging has the potential to support earlier treatment assessment and more timely therapeutic decision-making.

The talk will then focus on stromal remodeling as a biomarker of treatment response in pancreatic ductal adenocarcinoma (PDAC). PDAC is characterized by a dense desmoplastic stroma containing abundant extracellular matrix, particularly type I collagen. In patients with PDAC, higher post-treatment tumor fibrosis has been associated with longer overall survival, suggesting that assessment of treatment-induced stromal remodeling may provide information about therapeutic response. We therefore investigated whether treatment-induced changes in stromal fibrosis could be used to monitor and predict therapeutic response.

We first used a collagen-targeted PET probe to evaluate treatment-induced changes in tumor fibrosis in PDAC. In mouse models, collagen PET detected increased tumor collagen in treatment-responsive tumors but not in treatment-resistant tumors, allowing responders to be distinguished from nonresponders. We further showed that collagen-targeted PET uptake increased following neoadjuvant treatment in patients with PDAC. Because collagen deposition requires time to accumulate to detectable levels, we next investigated allysine, a biomarker of active fibrogenesis, as an earlier indicator of treatment response. Allysine-targeted molecular MRI detected treatment-induced fibrogenesis shortly after a single dose of FOLFIRINOX and distinguished subsequent responders from nonresponders.

Presenter Biography:
Hua Ma received his B.Sc. in Chemistry from Northeast Forestry University, China, in 2013 and his Ph.D. from Dalian University of Technology in 2019. He subsequently joined the laboratory of Prof. Peter Caravan at Massachusetts General Hospital and Harvard Medical School as a postdoctoral fellow, where he expanded his research to the development of MRI and PET probes for noninvasive imaging of active fibrogenesis. His work integrates coordination chemistry, molecular probe design, and in vivo imaging to enable noninvasive imaging of active fibrogenesis in models of fibrotic disease. He has also applied fibrosis-targeted imaging to predict therapeutic response in cancer. He is currently an Instructor in Radiology at Harvard Medical School and Massachusetts General Hospital. His research focuses on the design and translational development of imaging and therapeutic agents, including MRI and PET probes and radioligand therapeutics. By targeting extracellular biomarkers involved in fibrosis and cancer, his work aims to connect molecular design, disease biology, and clinical translation to advance precision imaging and therapy.

Author
Hua Ma
Harvard Medical School