Current status of theranostics in prostate cancer

Abstract

The aim of this review is to report on the current status of prostate-specific membrane antigen (PSMA)-directed theranostics in prostate cancer (PC) patients. The value of 68Ga-PSMA-directed PET imaging as a diagnostic procedure for primary and recurrent PC as well as the role of evolving PSMA radioligand therapy (PRLT) in castration-resistant (CR)PC is assessed. The most eminent data from mostly retrospective studies currently available on theranostics of prostate cancer are discussed. The current knowledge on 68Ga-PSMA PET/CT implicates that primary staging with PET/CT is meaningful in patients with high-risk PC and that the combination with pelvic multi parametric (mp)MR (or PET/mpMR) reaches the highest impact on patient management. There may be a place for 68Ga-PSMA PET/CT in intermediate-risk PC patients as well, however, only a few data are available at the moment. In secondary staging for local recurrence, 68Ga-PSMA PET/mpMR is superior to PET/CT, whereas for distant recurrence, PET/CT has equivalent results and is faster and cheaper compared to PET/mpMR. 68Ga-PSMA PET/CT is superior to 18F / 11Choline PET/CT in primary staging as well as in secondary staging. In patients with biochemical relapse, PET/CT positivity is directly associated with prostate-specific antigen (PSA) increase and amounts to roughly 50% when PSA is raised to ≤0.5 ng/ml and to ≥90% above 1 ng/ml. Significant clinical results have so far been achieved with the subsequent use of radiolabeled PSMA ligands in the treatment of CRPC. Accumulated activities of 30 to 50 GBq of 177Lu-PSMA ligands seem to be clinically safe with biochemical response and PERCIST/RECIST response in around 75% of patients along with xerostomia in 5–10% of patients as the only notable side effect. On the basis of the current literature, we conclude that PSMA-directed theranostics do have a major clinical impact in diagnosis and therapy of PC patients. We recommend that 68Ga-PSMA PET/CT should be performed in primary staging together with pelvic mpMR in high-risk patients and in all patients for secondary staging, and that PSMA-directed therapy is a potent strategy in CRPC patients when other treatment options have failed. The combination of PSMA-directed therapy with existing therapy modalities (such as 223Ra-chloride or androgen deprivation therapy) has to be explored, and prospective clinical multicenter trials with theranostics are warranted.

Clinical translation of theranostic radiopharmaceuticals: Current regulatory status and recent examples

“…It received marketing authorization in Europe and the US in 2018, together with its “companion diagnostic” a kit formulation for Ga‐68 labelling as Edotreotide (DOTATOC) in the EU (Somakit TOC) and DOTATATE in the US (NetSpot), being the first peptide‐based theranostic for wider clinical use. A second stimulus originated from the introduction of PSMA targeting ligands for diagnosis and therapy in prostate cancer . [ 68 Ga]Ga ‐PSMA ‐11 has proven to be a highly sensitive and specific marker for early detection and localization of prostate lesions in the biochemical recurrence stage and other clinical indications.…”

Initial evaluation of PET/CT with 18F‐FSU‐880 targeting prostate‐specific membrane antigen in prostate cancer patients

“…Recently, 18 F‐labeled PSMA inhibitors have also been developed and used clinically . Furthermore, PSMA inhibitors labeled with the β‐emitter, 177 Lu, and the α‐emitter, 225 Ac, have been introduced for PSMA‐targeted radioligand therapy and have yielded promising therapeutic results …”

“…Although PSMA-targeted imaging in prostate cancer was initially carried out using radiolabeled anti-PSMA Abs, the use of radiolabeled small molecular weight PSMA inhibitors is becoming more popular. 11,12 The clinical utility of PET/computed tomography (CT) using 68 Ga-labeled PSMA inhibitors, such as 68 Ga-PSMA-11, which is the most widely used inhibitor, has been reported in many papers. 13,14 Recently, 18 F-labeled PSMA inhibitors have also been developed and used clinically.…”

“…15,16 Furthermore, PSMA inhibitors labeled with the β-emitter, 177 Lu, and the α-emitter, 225 Ac, have been introduced for PSMA-targeted radioligand therapy and have yielded promising therapeutic results. 12,17,18 Despite the worldwide application of PSMA-targeted ligands in the imaging and treatment of prostate cancer, prostate cancer patients in Japan are unable to benefit from these PSMA-targeted probes.…”

Editorial Comment: Advances in MRI and PET of the prostate: concurrence or complementarity?

“…A preliminary clinical series in PCa of PET/ CT with radiotracer combining ligands of integrin α v β 3 and gastrin-releasing peptide receptor reported better results than with a radioligand binding to GRPR alone [15]. One major goal of this blossoming clinical research on PET radiotracers is the theranostic approach to select, based on PET, those patients who will be eligible for targeted radiotherapy using the same tracer labelled with a radionuclide designed for the destruction of tumours and of invisible spread [16,17].…”