Modeling and Predicting Tumor Response in Radioligand Therapy

Abstract

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 Lu-labeled PSMA for imaging and therapy (PSMA I&T). A recently developed PBPK model forLu 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. 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. 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.

Technical Note: Optimal sampling schedules for kidney dosimetry based on the hybrid planar/SPECT method in 177Lu‐PSMA therapy

“…The used patient cohort is described in detail elsewhere . In brief, 13 patients [age: (70 ± 6) yr] with mCRPC [median (range) total tumor volume: 236 ml (12, 5800 ml)] underwent 177 Lu‐PSMA I&T therapy [activity: (7.3 ± 0.3) GBq, peptide amount: (91 ± 5) nmol].…”

“…Virtual patients (P 1 –P 13 ) were created by fitting a whole‐body physiologically based pharmacokinetic (PBPK) model to the biokinetic data. The PBPK model is described elsewhere . The virtual patients were then used to simulate TACs of the kidneys (Fig.…”

“…The used patient cohort is described in detail elsewhere. 1,16,17 In brief, 13 patients [age: (70 AE 6) yr] with mCRPC [median (range) total tumor volume: 236 ml (12, 5800 ml)] underwent 177 Lu-PSMA I&T therapy [activity: (7.3 AE 0.3) GBq, peptide amount: (91 AE 5) nmol]. The individual biokinetics were measured with planar whole-body scans at 30-120 min, 24 h, and 7 days post injection (p.i.).…”

“…The PBPK model is described elsewhere. [16][17][18] The virtual patients were then used to simulate TACs of the kidneys (Fig. 1), which were used as ground truth.…”

Cardiac innervation imaging as a risk stratification tool for potential device therapy candidates

“…Aiming at tailored medical treatment for different tumor entities, efforts in nuclear oncology aimed to provide decision-support in disease management, e.g., by identifying the prognostic capability of baseline somatostatin-receptor PET in neuroendocrine tumor patients scheduled for peptide receptor radionuclide therapy or the prognostic performance of prostate-specific membrane antigen PET in prostate cancer patients. 19,20 Thus, if we aim to deliver on the promise of cardiac innervation imaging as a powerful tool for risk stratification among HF patients in a manner similar to nuclear oncology, studies such as the one reviewed here may imply an important step to lay the proper groundwork for a more widespread adoption in clinical practice.…”