Modeling and predicting tumor response in radioligand therapy

The aim of this work was to develop a theranostic method that allows predicting PSMA-positive tumor volume after radioligand therapy (RLT) based on a pre-therapeutic PET/CT measurement and physiologically based pharmacokinetic/dynamic (PBPK/PD) modeling at the example of RLT using 177Lu-labeled PSMA for imaging and therapy (PSMA I&T). Methods: A recently developed PBPK model for 177Lu PSMA I&T RLT was extended to account for tumor (exponential) growth and reduction due to irradiation (linear quadratic model). Data of 13 patients with metastatic castration-resistant prostate cancer (mCRPC) were retrospectively analyzed. Pharmacokinetic/dynamic parameters were simultaneously fitted in a Bayesian framework to PET/CT activity concentrations, planar scintigraphy data and tumor volumes prior and post (6 weeks) therapy. The method was validated using the leave-one-out Jackknife method. The tumor volume post therapy was predicted based on pre-therapy PET/CT imaging and PBPK/PD modeling. Results: The relative deviation of the predicted and measured tumor volume for PSMA-positive tumor cells (6 weeks post therapy) was 1±40% excluding one patient (PSA negative) from the population. The radiosensitivity for the PSA positive patients was determined to be 0.0172±0.0084 Gy-1. Conclusion: The proposed method is the first attempt to solely use PET/CT and modeling methods to predict the PSMA-positive tumor volume after radioligand therapy. Internal validation shows that this is feasible with an acceptable accuracy. Improvement of the method and external validation of the model is ongoing.

Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2018 May 10 [Epub ahead of print]

Peter Kletting, Anne Thieme, Nina Eberhardt, Andreas Rinscheid, Calogero D'Alessandria, Jakob Allmann, Hans-Jürgen Wester, Robert Tauber, Ambros J Beer, Gerhard Glatting, Matthias Eiber

Department of Nuclear Medicine, Ulm University, Ulm, Germany., Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München., Technische Universität München, Germany., Department of Urology, Klinikum Rechts der Isar, Technische Universität München., Medical radiation physics, Department of Nuclear Medicine, Ulm University.