Clinical perspectives of PSMA PET/MRI for prostate cancer

Abstract

Prostate cancer imaging has become an important diagnostic modality for tumor evaluation. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) has been extensively studied, and the results are robust and promising. The advent of the PET/magnetic resonance imaging (MRI) has added morphofunctional information from the standard of reference MRI to highly accurate molecular information from PET. Different PSMA ligands have been used for this purpose including 68gallium and 18fluorine-labeled PET probes, which have particular features including spatial resolution, imaging quality and tracer biodistribution. The use of PSMA PET imaging is well established for evaluating biochemical recurrence, even at low prostate-specific antigen (PSA) levels, but has also shown interesting applications for tumor detection, primary staging, assessment of therapeutic responses and treatment planning. This review will outline the potential role of PSMA PET/MRI for the clinical assessment of PCa.

Figure 1

PSMA PET/MRI for initial staging of a 77-year-old high-risk PCa patient with a Gleason score of 7 (3+4) and a PSA of 44.0 ng/dL. The staging would be T3bN1M0 if the patient was assessed with conventional imaging, namely, mpMRI (B and D) and BS (F). PSMA PET (coronal maximum intensity projection (MIP)inf A and fused PET/MR in C and E) clearly depicts more extensive pelvic (white arrows in A), extrapelvic thoracic and right inferior cervical nodal involvement (black arrows in A), upstaging the patient to T3bN1M1a. The incremental value of multimodal assessment is also seen in terms of the patient's T status. There is concordance between PSMA PET and MRI regarding bilateral seminal vesicle involvement encompassing the whole right seminal vesicle and the medial portion of the left seminal vesicle (white arrowheads in B and C), whereas PSMA PET/MRI revealed a more extensive (black long arrow in E) primary lesion in the left and median peripheral zones of base and midgland than mpMRI (white long arrows in D and E).

Figure 2

Evaluation of BCR in a 68-year-old patient treated with prostatectomy with a Gleason 7 adenocarcinoma (8 years) and prostate bed radiation (3 years), with a current PSA level of 0.29 ng/ml. ⁶⁸Ga-PSMA-fused PET/MRI MIP images (A) demonstrated 2 pathologic areas of focal uptake in the pelvis (black arrows). Axial T2-weighted imaging (B) showed nonspecific bilateral hypointense tissue in the prostate bed (arrowheads); however, T1-weighted perfusion imaging (C) demonstrated hypervascularity in the left tissue (arrowhead), which also had focal PSMA uptake on fused PET/MR imaging (D), confirming local recurrence. Moreover, a 4-mm left external iliac lymph node (white arrow) was almost not visible on axial T2-weighted imaging (E) but had focal uptake on fused imaging (F), which was very suspicious for pelvic nodal recurrence.

Figure 3

Example of different biological behaviors of PCa with treatment assessed by different tracers: (A) FDG PET in patient with advanced PCa showing retroperitoneal nodal and diffuse bone disease; (B) After beginning ADT, FDG PET shows a marked reduction in FDG uptake in the lesions; (C) PCa has become resistant to castration. Note subtle increase in diffuse FDG uptake in the skeleton. (D) At the same timepoint as C, PSMA PET was performed, showing marked bone disease, leading to an improved assessment of disease extension; and (E) PSMA PET performed 4 months after chemotherapy shows partial reduction in PSMA expression of diffuse skeletal involvement.

Figure 4

PSMA PET showing long-term PSMA expression against ADT in a patient with recurrent PCa who previously underwent pelvic radiation. The bottom row shows a bone metastatic lesion in left ischiatic tuberosity. The top row shows a new PSMA PET scan performed 10 months after beginning ADT, with resolution of the molecular expression of PSMA, probably reflecting a therapeutic effect of ADT.