Delphi consensus project on prostate-specific membrane antigen (PSMA)–targeted surgery—outcomes from an international multidisciplinary panel

Berrens, Anne-Claire; Scheltema, Matthijs; Maurer, Tobias; Hermann, Ken; Hamdy, Freddie C.; Knipper, Sophie; Dell’Oglio, Paolo; Mazzone, Elio; de Barros, Hilda A.; Sorger, Jonathan M.; van Oosterom, Matthias N.; Stricker, Philip D.; van Leeuwen, Pim J.; Rietbergen, Daphne D. D.; Valdes Olmos, Renato A.; Vidal-Sicart, Sergi; Carroll, Peter R.; Buckle, Tessa; van der Poel, Henk G.; van Leeuwen, Fijs W. B.

doi:10.1007/s00259-023-06524-6

Cited by 4 publications

(2 citation statements)

References 37 publications

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“…Acceleration of the excretion rate can for instance be achieved by coadministration of diuretics. Longer time intervals between imaging agent administration and surgery also help to minimize background signals but may also be considered unfavourable for clinical logistics and do require highly stable receptor-target binding without significant dissociation or metabolization [80].…”

Section: Effect Dosing On Signal Intensitymentioning

confidence: 99%

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Lessons learned in application driven imaging agent design for image-guided surgery

Buckle,

Rietbergen,

de Wit -van der Veen

et al. 2024

Eur J Nucl Med Mol Imaging

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To meet the growing demand for intraoperative molecular imaging, the development of compatible imaging agents plays a crucial role. Given the unique requirements of surgical applications compared to diagnostics and therapy, maximizing translational potential necessitates distinctive imaging agent designs. For effective surgical guidance, exogenous signatures are essential and are achievable through a diverse range of imaging labels such as (radio)isotopes, fluorescent dyes, or combinations thereof. To achieve optimal in vivo utility a balanced molecular design of the tracer as a whole is required, which ensures a harmonious effect of the imaging label with the affinity and specificity (e.g., pharmacokinetics) of a pharmacophore/targeting moiety. This review outlines common design strategies and the effects of refinements in the molecular imaging agent design on the agent’s pharmacological profile. This includes the optimization of affinity, pharmacokinetics (including serum binding and target mediated background), biological clearance route, the achievable signal intensity, and the effect of dosing hereon.

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Section: Effect Dosing On Signal Intensitymentioning

confidence: 99%

“…In addition, Delphi initiatives that focus on establishing the clinical demand in the form of e.g. timing, surgical readout [80] and preferred trial protocols are thought to help to substantially increase the translational success rate.…”

Section: Signal Intensitymentioning

confidence: 99%

Lessons learned in application driven imaging agent design for image-guided surgery

Buckle,

Rietbergen,

de Wit -van der Veen

et al. 2024

Eur J Nucl Med Mol Imaging

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First-in-human validation of a DROP-IN β-probe for robotic radioguided surgery: defining optimal signal-to-background discrimination algorithm

Collamati,

Morganti,

van Oosterom

et al. 2024

Eur J Nucl Med Mol Imaging

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Purpose In radioguided surgery (RGS), radiopharmaceuticals are used to generate preoperative roadmaps (e.g., PET/CT) and to facilitate intraoperative tracing of tracer avid lesions. Within RGS, there is a push toward the use of receptor-targeted radiopharmaceuticals, a trend that also has to align with the surgical move toward minimal invasive robotic surgery. Building on our initial ex vivo evaluation, this study investigates the clinical translation of a DROP-IN β probe in robotic PSMA-guided prostate cancer surgery. Methods A clinical-grade DROP-IN β probe was developed to support the detection of PET radioisotopes (e.g., 68 Ga). The prototype was evaluated in 7 primary prostate cancer patients, having at least 1 lymph node metastases visible on PSMA-PET. Patients were scheduled for radical prostatectomy combined with extended pelvic lymph node dissection. At the beginning of surgery, patients were injected with 1.1 MBq/kg of [68Ga]Ga-PSMA. The β probe was used to trace PSMA-expressing lymph nodes in vivo. To support intraoperative decision-making, a statistical software algorithm was defined and optimized on this dataset to help the surgeon discriminate between probe signals coming from tumors and healthy tissue. Results The DROP-IN β probe helped provide the surgeon with autonomous and highly maneuverable tracer detection. A total of 66 samples (i.e., lymph node specimens) were analyzed in vivo, of which 31 (47%) were found to be malignant. After optimization of the signal cutoff algorithm, we found a probe detection rate of 78% of the PSMA-PET-positive samples, a sensitivity of 76%, and a specificity of 93%, as compared to pathologic evaluation. Conclusion This study shows the first-in-human use of a DROP-IN β probe, supporting the integration of β radio guidance and robotic surgery. The achieved competitive sensitivity and specificity help open the world of robotic RGS to a whole new range of radiopharmaceuticals.

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Intraoperative molecular imaging – a means to strengthen the connection between nuclear medicine and surgical disciplines

van Leeuwen,

Chiti

2024

Eur J Nucl Med Mol Imaging

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Delphi consensus project on prostate-specific membrane antigen (PSMA)–targeted surgery—outcomes from an international multidisciplinary panel

Cited by 4 publications

References 37 publications

Lessons learned in application driven imaging agent design for image-guided surgery

Lessons learned in application driven imaging agent design for image-guided surgery

First-in-human validation of a DROP-IN β-probe for robotic radioguided surgery: defining optimal signal-to-background discrimination algorithm

Intraoperative molecular imaging – a means to strengthen the connection between nuclear medicine and surgical disciplines

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