Imaging cellular proliferation as a measure of response to therapy

Cell proliferation imaging is based on extensive laboratory investigations of labeled thymidine being selectively incorporated into DNA. [¹¹C]-Thymidine labeled in the ring-2 or the methyl position is the natural extension of earlier work using tritiated thymidine. Proliferation imaging using [¹¹C]-thymidine requires correction for labeled metabolites; however, quantitative approaches can provide reliable estimates of cellular proliferation by measuring thymidine flux from the blood into DNA in tumors. ¹⁸F-labeled thymidine analogs that are resistant to catabolism in vivo, [¹⁸F]-FLT and [¹⁸F]-FMAU, may simplify quantitative analysis and may be more suitable for clinical studies but will require careful validation to determine how their uptake is quantitatively related to cell growth. Clinical studies using [¹¹C]-thymidine have demonstrated the power of cellular proliferation imaging to characterize tumors and monitor response early in the course of therapy. Patient imaging using the PET thymidine analogs is at an earlier stage but appears promising as a clinically feasible approach to cellular proliferation imaging.