Prostate-Specific Membrane Antigen–Guided Surgery

Maurer, Tobias; Graefen, Markus; Poel, Henk van der; Hamdy, Freddie C.; Briganti, Alberto; Eiber, Matthias; Wester, Hans‐Jürgen; Leeuwen, Fijs W. B. van

doi:10.2967/jnumed.119.232330

Cited by 35 publications

(55 citation statements)

References 73 publications

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“…The multifunctionality of colloidal and nanoparticles is attractive for both active and passive targeting of tumors for image-guided surgery. The excitement about the targeting of imageable cancer biomarkers has stimulated interest in the development of many radiopharmaceuticals and fluorescent dye conjugates of tumor-targeting small molecules, peptides, and antibodies (12,14). In general, contrast agents that have short half-lives (minutes) may not be suitable for MIGS for logistic reasons, including time from the imaging suite to the OR.…”

Section: Exogenous Contrastmentioning

confidence: 99%

“…Freehand SPECT has also been used to guide SLN biopsy during breast (45) and oral (46) cancer surgeries. When used in conjunction with cancer-targeting radiopharmaceuticals (14), radioguided surgery is an excellent method to rapidly identify cancer, guide tumor resection, and survey the cavity after bulk tumor removal to minimize residual disease. A considerable limitation of this approach is the regulatory hurdles to use and maintain radiopharmaceuticals, confining this technique to specialized surgical centers.…”

Section: Nuclear Imagingmentioning

confidence: 99%

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Repurposing Molecular Imaging and Sensing for Cancer Image–Guided Surgery

et al. 2020

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Gone are the days when medical imaging was used primarily to visualize anatomic structures. The emergence of molecular imaging (MI), championed by radiolabeled 18 F-FDG PET, has expanded the information content derived from imaging to include pathophysiologic and molecular processes. Cancer imaging, in particular, has leveraged advances in MI agents and technology to improve the accuracy of tumor detection, interrogate tumor heterogeneity, monitor treatment response, focus surgical resection, and enable image-guided biopsy. Surgeons are actively latching on to the incredible opportunities provided by medical imaging for preoperative planning, intraoperative guidance, and postoperative monitoring. From label-free techniques to enabling cancer-selective imaging agents, imageguided surgery provides surgical oncologists and interventional radiologists both macroscopic and microscopic views of cancer in the operating room. This review highlights the current state of MI and sensing approaches available for surgical guidance. Salient features of nuclear, optical, and multimodal approaches will be discussed, including their strengths, limitations, and clinical applications. To address the increasing complexity and diversity of methods available today, this review provides a framework to identify a contrast mechanism, suitable modality, and device. Emerging low-cost, portable, and user-friendly imaging systems make the case for adopting some of these technologies as the global standard of care in surgical practice.

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Section: Exogenous Contrastmentioning

confidence: 99%

Section: Nuclear Imagingmentioning

confidence: 99%

Repurposing Molecular Imaging and Sensing for Cancer Image–Guided Surgery

et al. 2020

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“…The disease with regional LNMs can be considered as locoregional progressive disease between localized disease and the oligometastatic disease or systemic metastatic disease with distant LNMs (20,21). Therefore, the aim of the present study was to investigate whether clinical nomograms (Briganti, MSKCC and Winter) can predict non-regional LNMs and to generate cutoff values to predict distant LNMs.…”

Section: Introductionmentioning

confidence: 99%

The Establishment of New Thresholds for PLND-Validated Clinical Nomograms to Predict Non-Regional Lymph Node Metastases: Using 68Ga-PSMA PET/CT as References

et al. 2021

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PurposePLND (pelvic lymph node dissection)-validated nomograms are widely accepted clinical tools to determine the necessity of PLND by predicting the metastasis of lymph nodes (LNMs) in pelvic region. However, these nomograms are in lacking of a threshold to predict the metastasis of extrareolar lymph nodes beyond pelvic region, which is not suitable for PLND. The aim of this study is to evaluate a threshold can be set for current clinical PLND-validated nomograms to predict extrareolar LN metastases beyond pelvic region in high-risk prostate cancer patients, by using 68Ga-PSMA PET/CT as a reference to determine LN metastases (LNMs).Experimental DesignWe performed a retrospective analysis of 57 high-risk treatment-naïve PC patients in a large tertiary care hospital in China who underwent 68Ga-PSMA-617 PET/CT imaging. LNMs was detected by 68Ga-PSMA-617 PET/CT and further determined by imaging follow-up after anti-androgen therapy. The pattern of LN metastatic spread of PC patients were evaluated and analyzed. The impact of 68Ga-PSMA PET/CT on clinical decisions based on three clinical PLND-validated nomograms (Briganti, Memorial Sloan Kettering Cancer Center, Winter) were evaluated by a multidisciplinary prostate cancer therapy team. The diagnostic performance and the threshold of these nomograms in predicting extrareolar LNMs metastasis were evaluated via receiver operating characteristic (ROC) curve analysis.ResultsLNMs were observed in 49.1% of the patients by 68Ga-PSMA PET/CT, among which 65.5% of LNMs were pelvic-regional and 34.5% of LNMs were observed in extrareolar sites (52.1% of these were located above the diaphragm). The Briganti, MSKCC and Winter nomograms showed that 70.2%-71.9% of the patients in this study need to receive ePLND according to the EAU and NCCN guidelines. The LN staging information obtained from 68Ga-PSMA PET/CT would have led to changes of planned management in 70.2% of these patients, including therapy modality changes in 21.1% of the patients, which were mainly due to newly detected non-regional LNMs. The thresholds of nomograms to predict non-regional LNMs were between 64% and 75%. The PC patients with a score >64% in Briganti nomogram, a score >75% in MSKCC nomogram and a score >67% in Winter nomogram were more likely to have non-regional LNMs. The AUCs (Area under curves) of the clinical nomograms (Briganti, MSKCC and Winter) in predicting non-regional LNMs were 0.816, 0.830 and 0.793, respectively.ConclusionsBy using 68Ga-PSMA PET/CT as reference of LNM, the PLND-validated clinical nomograms can not only predict regional LNMs, but also predict non-regional LNMs. The additional information from 68Ga-PSMA PET/CT may provide added benefit to nomograms-based clinical decision-making in more than two-thirds of patients for reducing unnecessary PLND. We focused on that a threshold can be set for current clinical PLND-validated nomograms to predict extrareolar LN metastases with an AUC accuracy of about 80% after optimizing the simple nomograms which may help to improve the efficiency for PC therapy significantly in clinical practice.

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“…In 2009 the interest in Cerenkov applications was revived, as Robertson et al was the first to demonstrate the application of PET radiotracers in combination with CLI for imaging cancer in vivo [44]. Since then, multiple Cerenkov applications emerged in the biomedical field such as: photo activation therapy, Cerenkov luminescence imaging dosimetry, radionuclide therapy monitoring [46][47][48][49]. CLI allowed rapid translation from pre-clinical into clinical practice, as it uses registered clinical radiopharmaceuticals.…”

Section: Clinical Application Of CLImentioning

confidence: 99%

“…Additionally, it proved difficult for a long time to bind fluorescent agents to tumour targeted probes. However, recently new tumour specific probes have been developed, one of them being a PSMA targeted fluorescent agents [47][48][49]. In the Netherlands Cancer Institute, an ongoing clinical trial (EudraCT Number: 2019-002393-31) evaluates OTL-78, a PSMA-targeted fluorescent agent, for intraoperative imaging of prostate cancer.…”

Section: Alternatives For CLImentioning

confidence: 99%

A new light on prostate cancer

Heuvel¹

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Ga-PSMA-11 as intraoperative margin assessment technology in prostate cancer surgery. This research includes both the pre-clinical in vitro performance evaluation of the technique, as well as a clinical feasibility trial. In addition, repeatability of the 68 Ga-PSMA-11 PET/CT in both static and dynamic PET acquisitions was investigated to determine uptake patterns and usability of preoperative 68 Ga-PSMA-11 PET/CT in the CLI workflow.Part I of this thesis focusses on the application of and requirements for intraoperative margin assessment techniques in prostate cancer surgery. Chapter 2 is a systematic review of the different options for intraoperative margin assessment in the operating room. The technical background of different methods is provided, the application in prostate cancer surgery, and the advantages and drawbacks for clinical implementation. Prior to investigating the feasibility of intraoperative margin assessment using CLI, the performance of 68 Ga-PSMA-11 for CLI needs to be evaluated. So far, CLI is only used with 18 F-FDG, thus a comparison of the performance with 68 Ga-PSMA-11 was executed in Chapter 3. This chapter further outlines the requirements for ex vivo usage of 68 Ga-PSMA-11 in humans, based on in vitro results.Part II of this thesis introduces the use of 68 Ga-PSMA-11 PET/CT in primary PCa for CLI optimization. In current clinical practise, patients undergo a diagnostic PSMA PET/CT scan and prostatectomy is scheduled approximately 4 to 6 weeks later. Since patients are included for 68 Ga-PSMA-11 CLI based on their preoperative PSMA PET/CT scan, similar uptake at the time of surgery needs to be ensured. Therefore, repeatability of 68 Ga-PSMA-11 uptake was investigated in a 4-week interval, which is described in Chapter 4. Next, in 68 Ga-PSMA-11 PET/CT scans the optimal time between injection and imaging is based on the contrast of tumour uptake and activity distribution in the rest of the body. It is unknown whether the same time point is required for CLI imaging, as with CLI only the contrast between benign and tumour tissue in the prostate is relevant for ex vivo imaging. Chapter 5 describes dynamic 68 Ga-PSMA-11 PET/CT scans in test-retest setting to evaluate the repeatability of early uptake in the prostate.Part III explores the use of 68 Ga-PSMA-11 CLI, as an intraoperative margin assessment technology. Intraoperative detection of PSM might aid a radical excision, thus improving the patients' outcome. To investigate the feasibility of the technique, the results of the first five patients included in the CLI study are discussed in Chapter 6. This interim analysis showed that CLI is feasible and safe for intraoperative application. Important clinical knowledge was acquired necessary to optimize the acquisition protocol and workflow. The study was continued and the results of CLI accuracy compared to histopathology are reported in Chapter 7. Furthermore, this chapter describes and characterizes a newly identified bioluminescence signal, which might influence the interpretation of the...

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Prostate-Specific Membrane Antigen–Guided Surgery

Cited by 35 publications

References 73 publications

Repurposing Molecular Imaging and Sensing for Cancer Image–Guided Surgery

Repurposing Molecular Imaging and Sensing for Cancer Image–Guided Surgery

The Establishment of New Thresholds for PLND-Validated Clinical Nomograms to Predict Non-Regional Lymph Node Metastases: Using 68Ga-PSMA PET/CT as References

A new light on prostate cancer

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