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The future of PSMA PET and WB MRI as next-generation imaging tools in prostate cancer

Abstract

Radiolabelled prostate-specific membrane antigen (PSMA)-based PET–CT has been shown in numerous studies to be superior to conventional imaging in the detection of nodal or distant metastatic lesions. 68Ga-PSMA PET–CT is now recommended by many guidelines for the detection of biochemically relapsed disease after radical local therapy. PSMA radioligands can also function as radiotheranostics, and Lu-PSMA has been shown to be a potential new line of treatment for metastatic castration-resistant prostate cancer. Whole-body (WB) MRI has been shown to have a high diagnostic performance in the detection and monitoring of metastatic bone disease. Prospective, randomized, multicentre studies comparing 68Ga-PSMA PET–CT and WB MRI for pelvic nodal and metastatic disease detection are yet to be performed. Challenges for interpretation of PSMA include tracer trapping in non-target tissues and also urinary excretion of tracers, which confounds image interpretation at the vesicoureteral junction. Additionally, studies have shown how long-term androgen deprivation therapy (ADT) affects PSMA expression and could, therefore, reduce tracer uptake and visibility of PSMA+ lesions. Furthermore, ADT of short duration might increase PSMA expression, leading to the PSMA flare phenomenon, which makes the accurate monitoring of treatment response to ADT with PSMA PET challenging. Scan duration, detection of incidentalomas and presence of metallic implants are some of the major challenges with WB MRI. Emerging data support the wider adoption of PSMA PET and WB MRI for diagnosis, staging, disease burden evaluation and response monitoring, although their relative roles in the standard-of-care management of patients are yet to be fully defined.

Key points

  • Next-generation imaging techniques have been found to affect prostate cancer disease state classifications as their increased sensitivity can result in stage migration.

  • Prostate-specific membrane antigen (PSMA) PET has been shown to have higher sensitivity and specificity in detecting nodal and metastatic lesions than conventional imaging. PSMA-derived tumour volume and total lesion PSMA are experimental quantitative volumetric measures for whole-body (WB) tumour burden with good prognostic value for progression-free survival and can be used in treatment response assessment.

  • 177Lu-labelled PSMA is a potential new line of therapy in patients with metastatic castration-resistant prostate cancer who have progressed on at least one line of chemotherapy.

  • WB MRI is showing increasing promise as an ‘all-in-one’ modality for cancer diagnosis and staging without the need for radiation exposure. WB MRI-derived markers include apparent diffusion coefficient (ADC), signal fat fraction (sFF) and proton density fat fraction (PDFF). ADC values are especially useful for assessing bone metastases; PDFF and sFF are emerging quantitative imaging biomarkers that might be useful in assessing nodal and bone marrow metastases.

  • Limitations of PSMA PET include tracer trapping in non-target tissue, PSMA flare phenomenon, limited availability and radiation exposure related to radiotracers. Limitations of WB MRI include long acquisition time, metal-related and motion-related artefacts, fat–water swapping, incidentalomas, differential diagnoses of findings and limited availability.

  • Well-designed, powered, randomized multicentre studies are needed to assess the value of PSMA PET, WB MRI and standard imaging for disease detection, disease burden evaluation and survival across different prostate cancer disease states.

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Fig. 1: Clinical case demonstrating use of alternative PSMA tracers and PET–MRI to identify disease recurrence in the vesicourethral junction region.
Fig. 2: Clinical case demonstrating the use of alternative PSMA tracers and multiparametric MRI to identify disease recurrence in the vesicourethral junction region.
Fig. 3: Clinical case demonstrating PSMA uptake in prostate cancer metastases and physiological variant uptake in ganglia.
Fig. 4: Motion artefact and image distortion around a metallic hip implant on WB MRI.
Fig. 5: Fat–water swap artefacts in Dixon sequence on WB MRI.

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Y.W., J.R.G., S.W. and S.A. researched data for the article. All authors contributed substantially to discussion of the content. Y.W., J.R.G., S.A. and V.K. wrote the article. Y.W., J.R.G., A.H., S.W., H.P., S.A. and V.K. reviewed and/or edited the manuscript before submission.

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Glossary

Echo-planar imaging

(EPI). An MRI pulse sequence in which data for the entire image is collected following a single radiofrequency excitation. It has the advantage of rapid image acquisition but with poor resolution.

B0

The B0 in MRI refers to the main static magnetic field (scanner magnetic field) used to polarize spins and is measured in teslas. The majority of MRI systems in clinical use are 1.5 T or 3 T.

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Wang, Y., Galante, J.R., Haroon, A. et al. The future of PSMA PET and WB MRI as next-generation imaging tools in prostate cancer. Nat Rev Urol 19, 475–493 (2022). https://doi.org/10.1038/s41585-022-00618-w

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