Aspects of 18F-PSMA-1007 PET/CT in prostate cancer: Biokinetics, dosimetry, protocol and diagnostic accuracy

Overview: Prostate cancer (PC)is the most common cancer in Sweden, and the leading cause of cancer death. Positronemission tomography with x-ray computed tomography (PET/CT) is an important imagingmethod for many cancers. A group of PET radiopharmaceuticals known as PSMA(prostate specific membrane antigen) ligands has been introduced for imaging ofPC. This thesis investigates aspects of the ligand ¹⁸F-PSMA-1007.

Paper I focuses on biokinetics and population leveldosimetry, paper II on optimal timing of imaging, paper III on diagnosticaccuracy for local lymph node metastases, paper IV on diagnostic accuracy oflocally advanced tumor growth. All subjects were patients referred to ourdepartment for a PSMA PET/CT.

Methods: Paper I enrolled 12patients to undergo eight PET/CT scans up to six hours after injection of ¹⁸F-PSMA-1007.We measured time-activity data in 22 organs and created a biokinetic compartmentmodel which we then used for dosimetry calculations. Paper II enrolled 195patients to undergo PSMA PET/CT one and two hours after injection of ¹⁸F-PSMA-1007.Three readers evaluated images at both time points, mainly looking formetastases. Paper III retrospectivelyincluded 104 patients who had performed a PSMA PET/CT for staging of PC, followedby prostatectomy with lymph node dissection. We compared PSMAPET/CT evaluations of local lymph node metastases to the histopathology resultsand calculated the diagnostic accuracy. Paper IV retrospectively  included 124 patients who had undergone bothmagnetic resonance imaging (MRI) and a PSMA PET/CT before a prostatectomy. Weevaluated local tumor growth with both MRI (one reader) and PSMA PET/CT (tworeaders). We used a novel semi-standardized method for the PSMA PET/CT andevaluated the interrater reliability.

Results: Theeffective dose coefficient for ¹⁸F-PSMA-1007 was 25µSv/MBq, comparable to similar radiopharmaceuticals. More metastases were foundin images obtained after two hours as compared to one hour, which may affect PCstaging and treatment planning. PSMA PET/CT had low sensitivity both for local lymphnode metastases (26%) and for identifying locally advanced tumor growth (54%), butmoderate to high specificity (98% and 76%) respectively. Interrater reliabilitywas weak to moderate (0.53–0.68) for the local tumor growth evaluation.

Summary: Thiswork has contributed to the current body of knowledge of basic dosimetry,protocol optimization and diagnostic accuracy concerning the relatively new PETradiotracer ¹⁸F-PSMA-1007.