PSMA Ligands for PET Imaging of Prostate Cancer

Schwarzenboeck, Sarah; Rauscher, Isabel; Bluemel, Christina; Fendler, Wolfgang P.; Rowe, Steven P.; Pomper, Martin G.; Afshar‐Oromieh, Ali; Herrmann, Ken; Eiber, Matthias

doi:10.2967/jnumed.117.191031

Cited by 174 publications

(177 citation statements)

References 92 publications

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“…Newer and more sensitive imaging studies (e.g., prostate-specific membrane antigen positron-emission tomography) have identified metastases in some patients with no evidence of metastases on conventional imaging. [11][12][13] The regulatory approvals of currently marketed treatments for metastatic castration-resistant prostate cancer were based on the results of clinical trials involving men with metastases that were detected on conventional imaging, such as a bone scan or CT. It is possible that more sensitive imaging tests could have identified metastases at baseline in many of the patients in our trial, particularly because of the requirement for a short PSA doubling time at trial entry.…”

Section: Discussionmentioning

confidence: 99%

Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer

et al. 2018

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BACKGROUNDApalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis. METHODSWe conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide (240 mg per day) or placebo. All the patients continued to receive androgen-deprivation therapy. The primary end point was metastasis-free survival, which was defined as the time from randomization to the first detection of distant metastasis on imaging or death. RESULTSA total of 1207 men underwent randomization (806 to the apalutamide group and 401 to the placebo group). In the planned primary analysis, which was performed after 378 events had occurred, median metastasis-free survival was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group (hazard ratio for metastasis or death, 0.28; 95% confidence interval [CI], 0.23 to 0.35; P<0.001). Time to symptomatic progression was significantly longer with apalutamide than with placebo (hazard ratio, 0.45; 95% CI, 0.32 to 0.63; P<0.001). The rate of adverse events leading to discontinuation of the trial regimen was 10.6% in the apalutamide group and 7.0% in the placebo group. The following adverse events occurred at a higher rate with apalutamide than with placebo: rash (23.8% vs. 5.5%), hypothyroidism (8.1% vs. 2.0%), and fracture (11.7% vs. 6.5%). CONCLUSIONSAmong men with nonmetastatic castration-resistant prostate cancer, metastasisfree survival and time to symptomatic progression were significantly longer with apalutamide than with placebo. (Funded by Janssen Research and Development; SPARTAN ClinicalTrials.gov number, NCT01946204.)

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Section: Discussionmentioning

confidence: 99%

Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer

et al. 2018

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“…The clinical limitations of nontargeted molecular imaging agents for prostate cancer (PCa) has led to an exponential increase of investigational targeted imaging agents for magnetic resonance imaging (MRI), positron emission tomography (PET), and single‐photon emission computed tomography (SPECT) in both preclinical and clinical research over the past five years . In particular, the use of targeted PET agents was found to be remarkably effective in the detection, staging, and active surveillance of PCa …”

Section: Methodsmentioning

confidence: 99%

Modular Synthesis of DOTA‐Metal‐Based PSMA‐Targeted Imaging Agents for MRI and PET of Prostate Cancer

Schmitthenner

Dobson

Jones

et al. 2019

Chemistry A European J

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A practical, convergent synthesis of prostate‐specific membrane antigen (PSMA) targeted imaging agents for MRI, PET, and SPECT of prostate cancer has been developed. In this approach, metals chelated to 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA) were placed on the side chains of lysine early in the synthesis to form imaging modules. These are coupled to targeting modules, in this case consisting of the PSMA‐binding urea DCL, bonded to an activated linker. The modular approach to targeted molecular imaging agents (TMIAs) offers distinct advantages. By chelating the MRI contrast metal Gd early, it doubles as a protecting group for DOTA. Standard coupling and deprotection steps may be utilized to assemble the modules into peptides, and the need for tri‐tert‐butyl protection of DOTA requiring removal by strong acid is averted. This enables mild conjugation of the imaging module to a wide variety of targeting agents in the final step. It was further discovered that two labile metals, La3+ or Ce3+, can be used as placeholders in DOTA during the synthesis, then transmetalated in mild acid by Cu2+, Ga3+, In3+, and Y3+, metals used in PET/SPECT. This enables the efficient synthesis of nonradioactive analogues of targeted molecular imaging agents that may be transported or stored until needed. A simple and mild two‐step transmetalation, involving de‐metalation in dilute acid, followed by rapid chelation of the radioactive metal, may be conveniently performed later at the clinic to provide the TMIAs for PET or SPECT.

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“…PSMA represents a large extracellular domain which can be targeted by ligands for imaging and treatment purposes . Expression of PSMA is increased in more aggressive PCa . Since the first report of the use of 68 Ga‐PSMA PET in 2012, there has been a growing body of evidence that this technique is superior to other imaging approaches, both in the primary as well as in the recurrence setting .…”

Section: Introductionmentioning

confidence: 99%

Use of gallium‐68 prostate‐specific membrane antigen positron‐emission tomography for detecting lymph node metastases in primary and recurrent prostate cancer and location of recurrence after radical prostatectomy: an overview of the current literature

Luiting¹,

Leeuwen

Busstra³

et al. 2019

BJU International

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ObjectivesTo review the literature to determine the sensitivity and specificity of gallium-68 prostate-specific membrane antigen ( 68 Ga-PSMA) positron-emission tomography (PET) for detecting pelvic lymph node metastases in patients with primary prostate cancer (PCa), and the positive predictive value in patients with biochemical recurrence (BCR) after initial curative treatment, and, in addition, to determine the detection rate and management impact of 68 Ga-PSMA PET in patients with BCR after radical prostatectomy (RP). Materials and MethodsWe performed a comprehensive literature search. Search terms used in MEDLINE, EMBASE and Science Direct were '(PSMA, 68 Ga-PSMA, 68 Gallium-PSMA, Ga-68-PSMA or prostate-specific membrane antigen)' and '(histology, lymph node, staging, sensitivity, specificity, positive predictive value, recurrence, recurrent or detection)'. Relevant abstracts were reviewed and full-text articles obtained where possible. References to and from obtained articles were searched to identify further relevant articles. ResultsNine retrospective and two prospective studies described the sensitivity and specificity of 68 Ga-PSMA PET for detecting pelvic lymph node metastases before initial treatment, which ranged from 33.3% to 100% and 80% to 100%, respectively. In eight retrospective studies, the positive predictive value of 68 Ga-PSMA PET in patients with BCR before salvage lymph node dissection ranged from 70% to 100%. The detection rate of 68 Ga-PSMA PET in patients with BCR after RP in the PSA subgroups <0.2 ng/mL, 0.2-0.49 ng/mL and 0.5 to <1.0 ng/ mL ranged from 11.3% to 50.0%, 20.0% to 72.7% and 25.0% to 87.5%, respectively. ConclusionThe review results showed that 68 Ga-PSMA PET had a high specificity for the detection of pelvic lymph node metastases in primary PCa. Furthermore, 68 Ga-PSMA PET had a very high positive predictive value in detecting lymph node metastases in patients with BCR. By contrast, sensitivity was only moderate; therefore, based on the currently available literature, 68 Ga-PSMA PET cannot yet replace pelvic lymph node dissection to exclude lymph node metastases. In the salvage phase, 68 Ga-PSMA PET had both a high detection rate and impact on radiotherapy planning in early BCR after RP. Keywords 68Ga-PSMA PET/CT, pelvic lymph node dissection, detection rate, pelvic lymph node metastases, #ProstateCancer, #PCSM Use of 68Ga-PSMA PET/CT after RP: review IQR, interquartile range; LNM, lymph node metastases. *Gallium-68 prostate-specific membrane antigen positron-emission tomography ( 68 Ga-PSMA PET)/MRI was used instead of 68 Ga-PSMA PET/CT. 208

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PSMA Ligands for PET Imaging of Prostate Cancer

Cited by 174 publications

References 92 publications

Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer

Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer

Modular Synthesis of DOTA‐Metal‐Based PSMA‐Targeted Imaging Agents for MRI and PET of Prostate Cancer

Use of gallium‐68 prostate‐specific membrane antigen positron‐emission tomography for detecting lymph node metastases in primary and recurrent prostate cancer and location of recurrence after radical prostatectomy: an overview of the current literature

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