Joint survey by AIMN, AIOM, AIRO, SIU, SIUrO, and Meet-URO about the use of PSMA PET imaging in prostate cancer in Italy: technical aspects and primary staging setting

18F-fluorodeoxyglucose (FDG or 18F-FDG) is the most widely used radiotracer forPositron Emission Tomography/Computed Tomography (PET/CT) imaging. However,using FDG for PET/CT imaging in prostate cancer is limited because a large fractionof prostate cancer shows limited FDG uptake. Previously, radiolabeled choline derivativesuch as 18F-fluorocholine and 11C-choline were considered as a more suitable alternativeto FDG for prostate cancer imaging. They are used as PET tracers for staging andrestaging of prostate cancer. Although the specificity of radiolabeled choline is quitehigh, the sensitivity is rather poor. Currently, targeting the prostate specific membraneantigen (PSMA) with molecular imaging agents has been increasingly investigated.PSMA is expressed in most prostate cancer and it is an ideal target for diagnosis andtreatment. There are many PSMA agents available nowadays. This article will givebrief overview about PSMA ligands for PET imaging and therapy of prostate cancer.

Simple SummaryProstate cancer continues to be the most frequently diagnosed form of cancer and the leading cause of cancer-related deaths among men. For a successful treatment plan and outcome, an early diagnosis, correct staging, and monitoring of treatment response are crucial. To improve this, a radiotracer could be used to target the two most abundant proteins overexpressed in prostate cancer: prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPR). To date, no such heterodimeric radiotracer is used in the clinic. In this study, we have preclinically characterized and evaluated a galium-68 labelled PSMA/GRPR-targeting radiotracer for PET imaging of prostate cancer. We hope that the findings from this study will be able to contribute to designing better heterodimeric ligands, promote clinical translation of a heterodimer, and serve as a step towards a first-in-human study.The development of radioligands targeting prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPR) has shown promising results for the imaging and therapy of prostate cancer. However, studies have shown that tumors and metastases can express such targets heterogeneously. To overcome this issue and to improve protein binding, radioligands with the ability to bind both PSMA and GRPR have been developed. Herein, we present the preclinical characterization of [68Ga]Ga-BQ7812; a PSMA/GRPR-targeting radioligand for the diagnostic PET imaging of prostate cancer. This study aimed to evaluate [68Ga]Ga-BQ7812 to promote the translation of such imaging probes into the clinic. [68Ga]Ga-BQ7812 demonstrated rapid and specific binding to both targets in a PSMA/GRPR-expressing PC3-pip cell line. Results from the biodistribution study in PC3-pip xenografted mice showed specific binding to both targets, with the highest activity uptake at 1 h pi in tumor (PSMA+/GRPR+, 10.4 ± 1.0% IA/g), kidneys (PSMA+, 45 ± 16% IA/g), and pancreas (GRPR+, 5.6 ± 0.7% IA/g). At 3h pi, increased tumour-to-organ ratios could be seen due to higher retention in the tumor compared with other PSMA or GRPR-expressing organs. These results, together with low toxicity and an acceptable estimated dosimetry profile (total effective dose = 0.0083 mSv/MBq), support the clinical translation of [68Ga]Ga-BQ7812 and represent a step towards its first clinical trial.

Imaging of prostate cancer has been a rapidly evolving field in recent years with the introduction of multiple new PET tracer agents. Introduction of novel imaging techniques into clinical practice requires careful evaluation, with the ultimate aims of improved patient outcomes, better sequencing of treatments, and cost effectiveness. The increased sensitivity and specificity of these new PET agents present both challenges and opportunities. We know they frequently change management, but are these effective management changes, and is it always in the best interests of the patients? This review will focus on recent publications that provide high-level evidence for the use of PET in prostate cancer. It will discuss studies that have evaluated the clinical impact of PET imaging in prostate cancer and will review a number of trials that demonstrate the potential of PET to change current standard of care, from diagnosis, to prognostic capabilities in men with metastatic prostate cancer. Evidence for the use of PET in prostate cancer is building with studies evaluating diagnostic accuracy of PET at all stages of prostate cancer. We review the evidence available, focusing on prospective trials that are measuring the impact of new technology on patient outcomes.

HomeRadioGraphicsVol. 37, No. 7 Previous ErrataFree AccessClinical PET Imaging in Prostate Cancer—ErratumKathryn L. Wallitt, Sairah R. Khan, Suraiya Dubash, Henry H. Tam, Sameer Khan, Tara D. BarwickKathryn L. Wallitt, Sairah R. Khan, Suraiya Dubash, Henry H. Tam, Sameer Khan, Tara D. BarwickKathryn L. WallittSairah R. KhanSuraiya DubashHenry H. TamSameer KhanTara D. BarwickPublished Online:Nov 13 2017https://doi.org/10.1148/rg.2017174014MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In Originally published in:RadioGraphics 2017;37(5):1512–1536 • https://doi.org/10.1148/rg.2017170035Clinical PET Imaging in Prostate CancerErratum in:RadioGraphics 2017;37(7):2208 • https://doi.org/10.1148/rg.2017174014Page 1516, Table 2, row 2: The uptake time for 68Ga-PSMA should be 60 minutes [not 30 minutes].Article HistoryPublished online: Nov 13 2017Published in print: Nov 2017 FiguresReferencesRelatedDetailsCited ByDelineation of the androgen-regulated signaling pathways in prostate cancer facilitates the development of novel therapeutic approachesDominikAwad, Thomas LPulliam, ChenchuLin, Sandi RWilkenfeld, Daniel EFrigo2018 | Current Opinion in Pharmacology, Vol. 41Accompanying This ArticleClinical PET Imaging in Prostate CancerSep 12 2017RadioGraphicsRecommended Articles High Accuracy of PSMA PET in Initial Staging of High-Risk Prostate CancerRadiology: Imaging Cancer2020Volume: 2Issue: 4Prostate-specific Membrane Antigen PET in Addition to Multiparametric Prostate MRI Triage in the Diagnosis of Prostate Cancer: The Future is AvidRadiology: Imaging Cancer2022Volume: 4Issue: 168Ga Prostate-specific Membrane Antigen PET/CT for Primary Diagnosis of Prostate Cancer: Complementary or Alternative to Multiparametric MR ImagingRadiology2018Volume: 287Issue: 2pp. 725-726Competitive Advantage of PSMA Theranostics in Prostate CancerRadiology2021Volume: 299Issue: 2pp. 261-263Imaging Biochemical Recurrence in Prostate CancerRadiology: Imaging Cancer2021Volume: 3Issue: 4See More RSNA Education Exhibits Biochemical Recurrence in Prostate Cancer: Rising Role of PET ImagingDigital Posters2018Prostate Cancer Imaging from A to Z: What Radiologists Need to KnowDigital Posters2020Radiologists in the Radiation Treatment Planning Room: How Increased Collaboration Between Prostate Imagers and Radiation Oncologists Fosters Best Practices in the Treatment of Prostate CancerDigital Posters2018 RSNA Case Collection Parasagittal meningiomaRSNA Case Collection2022Locally advanced, metastatic prostate adenocarcinomaRSNA Case Collection2020Radioembolization of Liver Metastasis RSNA Case Collection2020 Vol. 37, No. 7 Metrics Altmetric Score PDF download

PET imaging of prostate cancer

The association between regional norms of clinical practice and appropriateness of care is incompletely understood. Understanding regional patterns of care across diseases might optimize implementation of programs like Choosing Wisely, an ongoing campaign to decrease wasteful medical expenditures. To determine whether regional rates of inappropriate prostate and breast cancer imaging were associated. Retrospective cohort study using the the Surveillance, Epidemiology, and End Results-Medicare linked database. We identified patients diagnosed from 2004 to 2007 with low-risk prostate (clinical stage T1c/T2a; Gleason score, ≤6; and prostate-specific antigen level, <10 ng/mL) or breast cancer (in situ, stage I, or stage II disease), based on Choosing Wisely definitions. In a hospital referral region (HRR)-level analysis, our dependent variable was HRR-level imaging rate among patients with low-risk prostate cancer. Our independent variable was HRR-level imaging rate among patients with low-risk breast cancer. In a subsequent patient-level analysis we used multivariable logistic regression to model prostate cancer imaging as a function of regional breast cancer imaging and vice versa. We identified 9219 men with prostate cancer and 30,398 women with breast cancer residing in 84 HRRs. We found high rates of inappropriate imaging for both prostate cancer (44.4%) and breast cancer (41.8%). In the first, second, third, and fourth quartiles of breast cancer imaging, inappropriate prostate cancer imaging was 34.2%, 44.6%, 41.1%, and 56.4%, respectively. In the first, second, third, and fourth quartiles of prostate cancer imaging, inappropriate breast cancer imaging was 38.1%, 38.4%, 43.8%, and 45.7%, respectively. At the HRR level, inappropriate prostate cancer imaging rates were associated with inappropriate breast cancer imaging rates (ρ = 0.35; P < .01). At the patient level, a man with low-risk prostate cancer had odds ratios (95% CIs) of 1.72 (1.12-2.65), 1.19 (0.78-1.81), or 1.76 (1.15-2.70) for undergoing inappropriate prostate imaging if he lived in an HRR in the fourth, third, or second quartiles, respectively, of inappropriate breast cancer imaging, compared with the lowest quartile. At a regional level, there is an association between inappropriate prostate and breast cancer imaging rates. This finding suggests the existence of a regional-level propensity for inappropriate imaging utilization, which may be considered by policymakers seeking to improve quality of care and reduce health care spending in high-utilization areas.

Accurate staging is of utmost importance in patients with primary or recurrent prostate cancer. Current imaging techniques are unsuited for whole-body staging or limited by low sensitivity for small metastatic lesions. Prostate specific membrane antigen (PSMA) is over-expressed on prostate cancer cells. Thus, 68Ga-labelled small molecule PSMA ligands were developed to potentially overcome these limitations. A systematic search strategy was applied to review evidence for PSMA-directed imaging of prostate cancer. 175 publications were retrieved from The National Center for Biotechnology Information PubMed online database using the following search term: psma AND pet AND prostate cancer. Sixteen publications were included based on the following criteria: original research; cohort study; reported diagnostic accuracy at primary diagnosis or biochemical recurrence; high quality of data acquisition and analysis. 68Ga-PSMA PET/CT stages lymph node involvement with a higher accuracy than CT and 68Ga-PSMA PET/MRI more accurately localizes primary prostate cancer than MRI or PET alone. Especially in patients with serum PSA <1 ng/mL sites of biochemical recurrence were detected better with 68Ga-PSMA PET/CT than with any other imaging modality. In summary, PSMA imaging demonstrates high accuracy for prostate cancer staging at primary diagnosis and biochemical recurrence. Future trials need to determine whether this superior diagnostic performance translates into improved clinical outcomes.

The aim of this paper is to review the role of 18F-choline or 11C-cholinePET/CT in prostate cancer patients for diagnosis, staging and restaging in case of biochemical recurrence and on the use of 18F-choline or 11C-choline PET/CT for metastases directed salvage therapies and in castrate-resistant patients treated with systemic therapy. A literature search was performed, and articles related to 11C-choline and 18F-choline PET/CT in prostate cancer staging and biochemical relapse were identified. Search terms were: “PET” and “PET/CT”, “11C-choline”, “18F-choline”, “prostate cancer staging”, “lymph node staging” “biochemical recurrence”. We have reported the results of the most relevant publications following the criteria of clinical relevance, confirmations of choline PET/CT findings with histology, other imaging methods or clinical follow-up. Moreover, we have briefly reported about the use of 18F-choline or 11C-choline PET/CT for prostate cancer diagnosis and to monitor castrate-resistant prostate cancer (CRPC) patients treated with systemic therapy. In lymph node and distant staging choline, PET/CT showed low sensitivity but, in most of the cases, a relatively high specificity. In case of biochemical recurrence, PSA absolute value and PSA kinetics confirmed their strict correlation with choline PET/CT findings. Choline PET/CT resulted to be very useful to address salvages therapies, especially in the early phases of biochemical recurrence. The use of choline PET/CT in CRPC should be more deeply investigated. At the moment, its use in the diagnosis of prostate cancer is not recommended. 18F-choline or 11C-choline PET/CT provides useful information to clinicians mostly in case of biochemical recurrence, while the low sensitivity limits its use during staging.

Prostate cancer (PCa), one of the most common cancers in males, is a topic of active interest in imaging research. Positron emission tomography/computed tomography (PET/CT) and PET/magnetic resonance imaging (PET/MRI) have enabled the combination of morphologic and functional imaging with the promise of providing better information in guiding therapy. 18F-fluorodeoxyglucose, the workhorse radiopharmaceutical in PET imaging, has not found preference in PCa since these tumors show poor glucose uptake and can be obscured by the normal urinary excretion of the radiotracer. Hence, the last two decades have seen the development of multiple newer radiotracers and better optimization of the technical aspects of PET imaging. The combination of functional imaging and MRI holds great promise. We searched PubMed, Scopus, and Google Scholar for peer-reviewed literature concerning the advances and newer developments in the imaging of PCa between the years 2005 and 2017. This review aims at summarizing current evidence on the role of PET imaging in PCa and its impact on the diagnosis, staging, prognostication, response assessment, and restaging of this malignancy.

PET/CT Imaging and Radioimmunotherapy of Prostate Cancer

The aim of this review is to explore the clinical application of different PET radiopharmaceuticals in prostate cancer (PCa), beyond inhibitors of the prostate-specific membrane antigen (PSMA). Choline PET represented in the last decades the standard of reference for PET imaging in PCa and has been recently included in clinical trials evaluating the efficacy of metastasis-directed therapy in oligo-metastatic disease. Fluciclovine, as synthetic amino acid, has been proposed for investigating PCa. The results obtained by the first prospective studies led to FDA approval in 2016 in patients with biochemical recurrence. Recently, phase II/III trials explored its accuracy compared with PSMA PET and its impact on patient management. Imaging the gastrin-releasing polypeptide receptor (GRPR) recently drawn attention. Radio-labelled GRPR antagonists have the potential to be used as theranostic agents. Further evaluation is needed to understand the relation between GRPR expression and hormonal-resistant PCa, and for tumors characterized by heterogeneity of receptors expressed (e.g. PSMA-negative) on their cell surface. Other new generation PET tracers may play an important role in PCa, namely in case of PSMA-negative phenotypes.

The study aims to investigate the presence of physiologic prostate-specific membrane antigen (68Ga-PSMA)-ligand uptake on PET in cervical, celiac, and sacral ganglia of the sympathetic trunk as a pitfall for lymph node metastases in prostate cancer imaging. Methods: Four hundred seven patients who underwent Glu-NH-CO-NH-Lys radiolabeled with 68Ga-gallium N,N-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N-diacetic acid (68Ga-PSMA-HBED-CC) PET (combined with a diagnostic CT) were retrospectively analyzed. The number of 68Ga-PSMA PET-positive cervical, celiac, and sacral ganglia was determined, and the configuration and SUVmax of each ganglion were measured. In addition, the configuration and SUVmax of adjacent lymph node metastases in the respective region (cervical, celiac, or sacral) were determined. Results:68Ga-PSMA-ligand uptake above background was detected in 401 (98.5%) patients in any peripheral ganglia, in 369 (92%) patients in cervical ganglia, in 363 (89%) patients in celiac ganglia, and in 183 (46%) patients in sacral ganglia. The 68Ga-PSMA-ligand uptake was highest in celiac (mean SUVmax, 2.9 ± 0.8 vs. cervical mean SUVmax, 2.4 ± 0.6) and sacral (mean SUVmax 1.7 ± 0.5; both P < 0.0001) ganglia. Intraindividually there was a statistically significant but weak to moderate correlation between the 68Ga-PSMA-ligand uptake in cervical versus celiac ganglia (R = 0.34, P < 0.0001), cervical versus sacral (R = 0.52, P < 0.0001), and celiac versus sacral (R = 0.16, P < 0.05). The 68Ga-PSMA-ligand uptake was significantly more intense in adjacent lymph node metastases than the respective ganglia (cervical: 18.0 ± 16.2 vs. 2.4 ± 0.6, P < 0.0001; celiac: 13.5 ± 12.3 vs. 2.9 ± 0.8, P < 0.0001; sacral: 13.4 ± 11.6 vs. 1.7 ± 0.5, P < 0.0001). Furthermore, ganglia predominantly exhibit a band-shaped configuration (71.2%), followed by a teardrop (26.8%) and only rarely a nodular configuration (2.0%). Conversely, lymph node metastases are only rarely band-shaped (1.1%), but more often show teardrop (40.3%) or nodular appearance (58.6%) (P < 0.00001). Conclusion:68Ga-PSMA-ligand uptake in ganglia along the sympathetic trunk as assessed by 68Ga-PSMA-HBED-CC PET represents an important pitfall in prostate cancer PET imaging. The 68Ga-PSMA-ligand uptake is higher in celiac ganglia than cervical or sacral ganglia, and the level of 68Ga-PSMA-ligand uptake seems to be patient-related. For the differentiation between lymph node metastases and sympathetic ganglia, both intensity of 68Ga-PSMA-ligand uptake and exact localization and configuration of the respective lesion should be examined carefully.

Radiohybrid prostate-specific membrane antigen (rhPSMA) ligands are a novel class of radiopharmaceuticals developed for potential theranostic application in prostate cancer (PCa). We aimed to consolidate existing evidence on utility of 18 F-rhPSMA-7/7.3 for PET imaging in PCa in the setting of biochemical recurrence (BCR). A comprehensive literature search was performed using relevant keywords in PubMed, Scopus, and EMBASE. Articles evaluating utility of 18 F-rhPSMA-7/7.3 PET in PCa BCR, published through September 30, 2024, were included. rhPSMA PET detection rate (DR) in BCR was calculated on a per-patient basis, with pooled proportion and 95% confidence interval. Furthermore, pooled DRs using different cutoff values of serum prostate-specific antigen (PSA) were obtained. Five studies with 1513 patients (overall) were included. The pooled DR of 18 F-rhPSMA-7/7.3 PET in BCR was 81.7% (95% confidence interval: 76.3%-86.5%). The pooled DRs stratified by serum PSA levels were 60.7% for PSA <0.5ng/mL, 80.1% for PSA between 0.5 and <1.0ng/mL, 85.9% for PSA between 1.0 and <2.0ng/mL, and 95.1% for PSA ≥2.0ng/mL, respectively. Our results suggest that novel radiotracers 18 F-rhPSMA-7/7.3 have excellent diagnostic utility as PET imaging agents in BCR of PCa. Further prospective multicenter studies are required to validate these novel tracers in diverse clinical settings with larger patient cohorts and assess their diagnostic accuracy in comparison to the PSMA ligands in current clinical practice.

Prostate cancer is the second most common cancer in men. Its diagnosis and management are still challenging as both PSA levels and imaging have had their limitations. Prostate specific membrane antigen (PSMA) is aprostate specific cell surface protein and has been emerging as a novel target for PET imaging of prostate cancer. 68Ga PSMA PET-CT imaging have been shown as a better imaging technology in primary prostate cancer and at the same time detecting lymph node and bone metastases even in low PSA levels. Moreover, its counterpart 177 Lu PSMA has a great prospectto be used for the treatment of castration resistantprostate cancer.&#x0D; Bangladesh J. Nuclear Med. 22(1): 53-57, Jan 2019

The three main sections in this article illustrate a number of facets of European health care. The first section looks at the influence of NICE on treatment of metastatic castration-resistant prostate cancer. The second section explores the impact of molecular imaging on diagnosis and treatment, in particular the development and clinical implementation of 68Ga PET imaging in prostate cancer. The final section of the session looks at the STAMPEDE trial and how running a trial on this scale has impacted care of prostate cancer in the United Kingdom and also at the uptake of docetaxel chemotherapy in hormone-sensitive advanced disease.