Prostate-specific membrane antigen (PSMA)-based imaging in localized and advanced prostate cancer: a narrative review

Abstract

Combined molecular and morphologic imaging modalities have emerged in recent years as an alternative to conventional imaging in prostate cancer (PC). In particular, novel prostate-specific membrane antigen (PSMA) radiotracers have demonstrated increased sensitivity and specificity for the initial staging of men with clinically localized PC, as well as for PC detection in the setting of biochemical recurrence (BCR).Molecular imaging is increasingly used to guide treatment decisions in these patients-though its impact on survival has yet to be established. Improved PC detection in men with BCR has also helped to identify a subset of patients with oligometastatic disease. The optimal management of oligometastatic PC and the role of metastasis-directed therapies (MDT) are the subjects of ongoing studies. In comparison to clinically localized or biochemically recurrent PC, the role of molecular imaging in men with advanced disease is less established. In metastatic castration-resistant PC (mCRPC), PSMA-based imaging has primarily been investigated as a companion diagnostic tool to predict and monitor response to PSMA-targeted radioligand therapy (RLT). More recent efforts have focused on using molecular imaging to monitor treatment response to conventional chemohormonal therapies. However, despite promising early results, several barriers remain to the widespread use of PSMA-based imaging in metastatic PC: temporary flares in PSMA uptake have been described in a subset of patients after initiation of therapy, and the underlying mechanism and clinical implications of this phenomenon are still poorly understood. Furthermore, whereas PSMA is invariably expressed in hormone-sensitive PC, loss of PSMA expression is increasingly recognized in a subset of mCRPC patients with aggressive disease. Although this may limit the use of PSMA-based imaging as a standalone modality in advanced PC, loss of PSMA uptake may also provide non-invasive and clinically relevant molecular insight on patients' underlying tumor biology.

Evaluating appropriateness of 18F-fluciclovine PET/CT relative to standard of care imaging guidelines and the impact of ADT on positivity: a prospective study in 62 Veterans Administration patients at a single institution

“…Bidakhvidi et al also found positivity rate of 80% using 18F-PSMA-1007 in the detection of lesions in patients with BCR prostate cancer [20]. In addition, the literature from 177Lu-PSMA therapy studies has shown that 20-25% of metastatic castrate resistant prostate cancer (mCRPC) patients are excluded from clinical trials of 177Lu-PSMA therapy due to imaging demonstrating uniformly low PSMA uptake of lesions or discordant lesions showing low PSMA and high 18F-fluorodeoxyglucose (FDG) uptake [22][23][24]. For these patients, other PET imaging agents should be considered such as 18F-fluciclvovine, 18F-FDG, or Sarcophagine-Bombesin imaging agents.…”

The Application of Radiolabeled Targeted Molecular Probes for the Diagnosis and Treatment of Prostate Cancer

“…Therefore, [ 68 Ga]Ga-PSMA-I&T shows greater sensitivity for the detection of primary and metastatic periurethral PCa lesions compared with [ 68 Ga]Ga-PSMA-617, especially for high-grade PCa (GS 8 or above, PSA > 10 ng/mL). However, the kidneys have a much higher uptake of PSMA-I&T than PSMA-617, which is unfavorable for treatment [ 35 36 37 ].…”

Improvements in Prostate Cancer Management: Focus on Imaging and Treatment

“…1 Conventional imaging modalities used in prostate cancer have traditionally included CT, MRI, and 99m Tclabelled bisphosphonate bone scintigraphy. 2 Although widely available, these modalities have significant limitations, including poor sensitivity and specificity for metastatic disease. 3 A desire to find a better diagnostic imaging technique for prostate cancer led to a focus on prostate-specific membrane antigen (PSMA), which is highly overexpressed in most prostate carcinoma cells.…”

“…1 The most widely studied PSMA radioligand is 68 Ga-labelled PSMA-11 ( 68 Ga-PSMA-11 [ABX Advanced Biochemical Compounds GmbH, Radeberg, Germany]). 2,4 In the Telix-sponsored symposium, 'Improvements in prostate cancer management: focus on imaging and treatment' , delivered on 3 rd July 2022 at the 37 th EAU Annual Congress in Amsterdam, the Netherlands, speakers from three different specialties invited delegates to 'get on board the PSMA train' to optimise the imaging and treatment of prostate cancer, and help improve outcomes for patients.…”