VALUATION OF CHALLENGES IN SPECT-BASED DOSIMETRY IN THE TREATMENT OF METASTATIC PROSTATE CANCER WITH 177LU-PSMA-617

Abstract

Introduction: In nuclear medicine, targeted radioligand therapy is an established treatment option for metastatic cancer disease. A radioactive isotope is attached to a carrier molecule that will specifically bind to a certain target. One such example is the prostate-specific membrane antigen (PSMA); a transmembrane glycoprotein often highly expressed in metastatic prostate cancer tumors. Recently, 177Lu-PSMA-617 was approved by the Food and Drug Administration (FDA) for clinical treatment of prostate cancer patients under the name Pluvicto. This treatment was implemented at Sahlgrenska University Hospital in 2023 and to establishing a method of dosimetry for 177Lu-PSMA-617 is thus of great importance. The overall aim of the study was to evaluate some factors thar are challenging in 177Lu-PSMA-617 SPECT-based (single photon emission tomography) dosimetry. Method: This study included four patients, injected with 7.4 GBq of 177Lu-PSMA-617 for 1–6 treatment cycles, with 1 or 4 SPECT/CT images per treatment cycle (day 1 or day 0, 1, 2, and 7). All patients underwent a pre-therapeutic 68Ga-PSMA-11 PET/CT scan (positron emission tomography/computer tomography). A new SPECT protocol was established using three image field-of-views (FOVs), with 30 projections per FOV. The kidneys, submandibular, and parotid glands were manually outlined in the CT images. An analysis was performed to assess the uncertainties associated with manual segmentation. Subsequently, an attempt at establishing a threshold-based method for organ volume estimations using the pre-therapeutic 68Ga-PSMA-11 PET and the therapeutic 177Lu-PSMA-617 SPECT imaging was made. Repeated segmentations of the submandibular and parotid glands were performed in the CT images to obtain reference volumes. Varying thresholds of maximum activity were used to determine gland volumes in the PET and SPECT images. The volume differences could then be analyzed, and the optimal threshold decided. Furthermore, SPECT-based kidney dosimetry was conducted for each patient. Segmented kidney volumes were applied to the SPECT reconstruction. Activity was quantified and time-activity curves generated. These was then used to calculate the average absorbed kidney dose. Lastly, the correlation between absorbed dose in kidneys from SPECT and signal in kidneys from PET was evaluated. Results: Manual segmentations of the left and right parotid glands showed mean uncertainties of 2.6–19%. For the four patients, the optimal segmentation thresholds for the submandibular glands in SPECT were 57.4, 40.7, 39.9, and 35.8%, respectively, with mean uncertainty 21.2–49.6%. In PET, optimal thresholds for the submandibular and parotid glands were 34.1% and 30.2%, respectively, with a mean uncertainty of 4.9–13.9%. The average absorbed kidney doses were 3.0, 1.2, 3.8, and 3.3 Gy, respectively. There was a positive correlation between absorbed dose in SPECT and signal in PET with an R-value of 0.88. Conclusions: The accuracy of manual segmentations can be largely affected by artefacts, anatomical changes, and the judgement of the operator. This study demonstrates that a threshold-based method has the potential to be used for volume determination of the submandibular and parotid gland in PET imaging, with uncertainty similar to that of manual segmentation. A threshold-based segmentation would allow for a more efficient volume determination which would simplify the absorbed dose calculations. The calculated average absorbed kidney doses conformed to earlier studies, reinforcing current knowledge on the effects of 177Lu-PSMA-617. A correlation between absorbed dose in SPECT and signal in PET was observed, supporting the use of 68Ga-PSMA-11 PET as a predictor of 177Lu-SMA-617 absorbed dose.