EUO Priority Article and Collaborative Review – Prostate CancerEditorial by D. Murphy et al. on pp. 163–165 of this issueTheranostics for Advanced Prostate Cancer: Current Indications and Future Developments
Introduction
The word “theranostic” derives from Greek words therapeia (therapy) and gnosis (knowledge) and refers to the possibility of combining a diagnostic biomarker with a therapeutic agent [1].
This concept has been known since the end of the 20th century, with various applications currently available. Its first nuclear medical application dates back to 1946, when radioiodine therapy was first used to treat metastases of thyroid adenocarcinoma [2]. More recently, increased interest in theranostics led to the implementation of this combined approach to other clinical settings, including neuroendocrine tumors and advanced prostate cancer (PCa).
PCa is a leading cause of cancer mortality in men worldwide due to the development of metastatic disease [3]. Most patients with advanced disease initially respond to androgen deprivation therapy (ADT), but they develop invariably fatal castration-resistant PCa (CRPC) within 1–3 yr [4]. In 2004, two pivotal phase 3 studies demonstrated that docetaxel-based regimens improved overall survival (OS) in patients with CRPC [5], [6]. Since 2010, six new therapeutic agents with diverse mechanisms of action have been added to the available therapy arsenal, five of which (sipuleucel-T [7], cabazitaxel [8], abiraterone [9], enzalutamide [10], and radium-223 [11]) have been approved for the treatment of CRPC based on OS and progression-free survival (PFS) benefits. While these new treatments provided therapy tailoring options based on patient characteristics, none resulted in durable clinical responses, as the survival benefit was generally limited to <6 mo [10], [12]. Therefore, there is an unmet need for the development of new treatments.
During the last few years, prostate-specific membrane antigen (PSMA) ligands for positron emission tomography (PET) imaging have drawn the attention of the medical community. To date, the only Food and Drug Administration (FDA)-approved agent is the 111In-capromab pendetide (ProstaScint) for single-photon emission computed tomography (SPECT) imaging (1996), directed against an intracellular domain of PSMA [13], while the first human PSMA-PET study was performed in 2012 [14]. PSMA is a type II, carboxypeptidase-associated transmembranous glycoprotein with folate hydrolase activity [15]. It has been demonstrated that PSMA is overexpressed in PCa cells [16], and over the last few years, several radiolabeled PSMA ligands have been investigated in both PET and SPECT imaging. Additionally, current evidence suggests that a PSMA-targeting combined approach may provide not only a more accurate diagnosis, but also a realistic option to treat CRPC patients, for example, by employing ligands such as β-emitting isotopes, Auger emitters [17], or α-emitting isotopes.
Section snippets
Evidence acquisition
A board of nuclear medicine and urologist physicians, highly experienced in radionuclide imaging and radioligand therapy (RLT) in advanced PCa, conducted a nonsystematic review between February and March 2018 of the current indications, performance, limitations, and potential future developments of currently available theranostic options. Only articles published in English and deemed relevant to the topic were included in this review. Owing to the high number of radiotracers currently under
Different radiopharmaceuticals
Several radiotracers may be employed in the imaging of advanced PCa, namely, 18F-fludeoxyglucose (18F-FDG), 11C-choline, 18F-choline, 11C-acetate [18], 18F-acetate, 18F-fluciclovine (also known as FACBC) [19], dihydrotestosterone-based radiotracers such as 16β-18F-fluoro-5α-dihydrotestosterone [20], [21], [22], and radiolabeled bombesin receptor antagonists that targets gastrin-releasing peptide receptors [23], [24], [25] as well as other receptor-binding molecules [26], [27], [28]. To our
Conclusions
PSMA theranostics are revolutionizing imaging and therapy in advanced PCa patients. PSMA receptor-binding imaging may allow monitoring of systemic treatment and restaging prior to PSMA-directed RLT in metastatic disease. On the contrary, RLT may represent an available third-line treatment in CRPC patients and, in the near future, could be even considered an earlier option. However, further studies are needed to clarify its role in imaging and its performance. In addition, the challenges posed
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2022, Journal of EthnopharmacologyCitation Excerpt :In recent years, the incidence of PCa has been increasing rapidly in some Asian countries such as China, Korea, Thailand, etc. (Kimura and Egawa, 2018). Nevertheless, current treatments for PCa are frequently accompanied by side effects that affect the general health and quality of life of patients (Farolfi et al., 2019). Hence, it is urgent to find new therapies that effectively target PCa with low toxicity and few side effects.
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2021, Molecular Imaging: Principles and PracticeCurrent and potential applications of positron emission tomography for multiple myeloma and plasma cell disorders
2020, Best Practice and Research: Clinical HaematologyCitation Excerpt :In a phase 3 trial of 177Lu-DOTATATE for midgut NETs, the 116 patients receiving 177Lu-DOTATATE had a 65% progression-free survival (95% confidence interval 50–77%) at 20 months, compared with a 11% progression free-survival (95% confidence interval 4–23%) in the control group receiving a standard treatment agent, octreotide [26]. The concept of targeted imaging and therapy is being expanded to multiple malignances, with imaging and therapy targeting prostate-specific membrane antigen (PSMA) in prostate cancer demonstrating great promise [27–29]. Biomarker targets in plasma cell disorders that have recently been exploited for imaging and therapy include the chemokine receptor 4 (CXCR4), cluster of differentiation 38 (CD38), and B-cell maturation antigen (BCMA).
Synthesis and evaluation of novel radioiodinated PSMA targeting ligands for potential radiotherapy of prostate cancer
2020, Bioorganic and Medicinal ChemistryCitation Excerpt :Various treatment strategies, such as androgen ablation therapy, prostatectomy and chemotherapy, are available for different stages of PCa. However, ~35% of patients are expected to have biochemical recurrence within 10 years, and the survival benefit was generally limited to <6 months.2–5 Prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II (GCPII), is a trans-membrane protein primarily expressed at a low level on normal human prostate epithelium, but it is overexpressed at different stages of PCa.
Role of novel imaging in the management of prostate cancer
2019, Urologic Oncology: Seminars and Original InvestigationsCitation Excerpt :The most commonly studied and used tracer is the 68Ga-labeled PSMAHBED-CC (68Ga-PSMA) PET tracer. Notably, PSMA is the only theranostic (combination of a diagnostic biomarker with a therapeutic agent) available currently for prostate cancer [28]. Similarly to other PET tracers, PSMA has limited value in the detection and characterization of primary disease.