Non-invasive Early Response Monitoring of Nanoparticle-assisted Photothermal Cancer Therapy Using ¹⁸F-FDG, ¹⁸F-FLT, and ¹⁸F-FET PET/CT Imaging

Rationale: Since its first implementation nanoparticle-assisted photothermal cancer therapy has been studied extensively, although mainly with focus on optimal nanoparticle design. However, development of efficient treatment protocols, as well as reliable and early evaluation tools in vivo, are needed to push the therapy towards clinical translation. Positron emission tomography (PET) is a non-invasive imaging technique that is currently finding extensive use for early evaluation of cancer therapies; an approach that has become of increasing interest due to its great potential for personalized medicine. Methods: In this study, we performed PET imaging to evaluate the treatment response two days after nanoparticle-assisted photothermal cancer therapy in tumor-bearing mice. We used three different tracers; 2'-deoxy-2'-¹⁸F-fluoro-D-glucose (¹⁸F-FDG), 3'-deoxy-3'-¹⁸F-fluorothymidine (¹⁸F-FLT), and O-(2'-¹⁸F-fluoroethyl)-L-tyrosine (¹⁸F-FET) to image and measure treatment induced changes in glucose uptake, cell proliferation, and amino acid transport, respectively. After therapy, tumor growth was monitored longitudinally until endpoint was reached. Results: We found that nanoparticle-assisted photothermal therapy overall inhibited tumor growth and prolonged survival. All three PET tracers had a significant decrease in tumor uptake two days after therapy and these changes correlated with future tumor growth, with ¹⁸F-FDG having the most predictive value in this tumor model. Conclusion: This study shows that ¹⁸F-FDG, ¹⁸F-FLT, and ¹⁸F-FET are all robust markers for the treatment response of photothermal therapy, and demonstrate that PET imaging can be used for stratification and optimization of the therapy. Furthermore, having a selection of PET tracers that can reliably measure treatment response is highly valuable as the individual tracer might be excluded in certain applications where physiological processes limit their contrast to background.