Purpose: Currently, approximately 11–38% of prostate cancer (PCa) patients undergoing radical prostatectomy have a positive surgical margin (PSM) on histopathology. Cerenkov luminescence imaging (CLI) using ⁶⁸Ga-prostate-specific membrane antigen (⁶⁸Ga-PSMA) is a novel technique for intraoperative margin assessment. The aim of this first-in-man study was to investigate the feasibility of intraoperative ⁶⁸Ga-PSMA CLI. In this study, feasibility was defined as the ability to distinguish between a positive and negative surgical margin, imaging within 45 min and low radiation exposure to staff. Methods: Six patients were included in this ongoing study. Following perioperative i.v. injection of ~ 100 MBq ⁶⁸Ga-PSMA, the prostate was excised and immediately imaged ex vivo. Different acquisition protocols were tested, and hotspots on CLI images from the intact prostate were marked for comparison with histopathology. Results: By using an acquisition protocol with 150 s exposure time, 8 × 8 binning and a 550 nm shortpass filter, PSMs and negative surgical margins (NSMs) were visually correctly identified on CLI in 3 of the 5 patients. Two patients had a hotspot on CLI from cancer < 0.1 mm from the excision margin. Conclusion: Overall, the study showed that ⁶⁸Ga-PSMA CLI is a feasible and low-risk technique for intraoperative margin assessment in PCa. The remaining patients in this ongoing study will be used to assess the diagnostic accuracy of the technique. Trial registration: NL8256 registered at www.trialregister.nl on 04/11/20109.

Background: Recently, a flexible DROP-IN gamma-probe was introduced for robot-assisted radioguided surgery, using traditional low-energy SPECT-isotopes. In parallel, a novel approach to achieve sensitive radioguidance using beta-emitting PET isotopes has been proposed. Integration of these two concepts would allow to exploit the use of PET tracers during robot-assisted tumor-receptor-targeted. In this study, we have engineered and validated the performance of a novel DROP-IN beta particle (DROP-IN_β) detector. Methods: Seven prostate cancer patients with PSMA-PET positive tumors received an additional intraoperative injection of ~ 70 MBq ⁶⁸Ga-PSMA-11, followed by robot-assisted prostatectomy and extended pelvic lymph node dissection. The surgical specimens from these procedures were used to validate the performance of our DROP-IN_β probe prototype, which merged a scintillating detector with a housing optimized for a 12-mm trocar and prograsp instruments. Results: After optimization of the detector and probe housing via Monte Carlo simulations, the resulting DROP-IN_β probe prototype was tested in a robotic setting. In the ex vivo setting, the probe—positioned by the robot—was able to identify ⁶⁸Ga-PSMA-11 containing hot-spots in the surgical specimens: signal-to-background (S/B) was > 5 when pathology confirmed that the tumor was located < 1 mm below the specimen surface. ⁶⁸Ga-PSMA-11 containing (and PET positive) lymph nodes, as found in two patients, were also confirmed with the DROP-IN_β probe (S/B > 3). The rotational freedom of the DROP-IN design and the ability to manipulate the probe with the prograsp tool allowed the surgeon to perform autonomous beta-tracing. Conclusions: This study demonstrates the feasibility of beta-radioguided surgery in a robotic context by means of a DROP-IN_β detector. When translated to an in vivo setting in the future, this technique could provide a valuable tool in detecting tumor remnants on the prostate surface and in confirmation of PSMA-PET positive lymph nodes.

Objective Pelvic organ prolapse (POP) is clinically diagnosed in the supine position, where the effect of gravity is simulated by having the patients put strain on their pelvic floor. The objective of this study was to determine the degree of POP underestimation in the supine position based on magnetic resonance imaging (MRI) findings. Methods This prospective study was conducted with symptomatic POP grade ≥ 2 patients. Fifteen female patients were examined with an MRI system that allows supine and upright imaging. The differences between supine and upright in distances of the bladder neck, cervix, and pouch of Douglas from the pubococcygeal line (PCL) were estimated, together with changes in the genital hiatal area. Patients were scanned at rest and during straining. All distances were compared using the Wilcoxon ranking test. Results All mean distances from the PCL increased from the supine–strain to the upright–rest and from the supine–strain to the upright–strain position. These distances were found in the supine and upright positions: the bladder descended 1.3 cm to 1.4 cm, the cervix 1.1 cm to 2.2 cm, and the pouch of Douglas 0.8 cm to 1.5 cm respectively (all p values <0.05). The hiatal area was larger in the upright–strain position (mean 42.0 cm²; SD ±14.8) than during the supine–strain position (mean 33.5 cm²; SD ±14.5), with a p value of 0.02. Conclusion Upright MRI scanning of patients with POP grade ≥ 2 both at rest and during straining shows a significantly larger extent of the prolapse than that observed during supine straining.

The main challenge in radical prostatectomy is complete excision of malignant tissue, while preserving continence and erectile function. Positive surgical margins (PSMs) occur in up to 38% of cases, are associated with tumour recurrences, and may result in debilitating additional therapies. Despite surgical developments for prostate cancer (PCa), no technology is yet implemented to assess surgical margins of the entire prostatic surface intraoperatively. The aim of this systematic review is to provide an overview of novel imaging methods developed for intraoperative margin assessment in PCa surgery, which are compared with standard postoperative histopathology. A literature search of the last 10 yr was conducted in the Scopus, PubMed, and Embase (Ovid) databases. Eligible articles had to report the PSM rate according to their intraoperative margin assessment technology in comparison with standard histopathology. The search resulted in 616 original articles, of which 11 were included for full-text review. The main technical developments in PCa margin assessment included optical coherence tomography, photodynamic diagnosis with 5-aminolevulinic acid, spectroscopy, and enhanced microscopy. These techniques are described and their main advantages, limitations, and applications in the clinical setting are discussed. Several imaging methods are suggested in literature for the detection of positive margins during PCa surgery. Despite promising qualifications of the mentioned technologies, many struggle to find implementation in the clinic. Surgical conditions hampering the signal, long imaging times, and comparison with histopathology are mutual challenges. The next step towards reduction of PSMs in PCa surgery includes evaluation of these technologies in large clinical trials. In this review, new technologies are reported that can assist the surgeon by detecting insufficient removal of all tumorous tissue during surgery, instead of the standard postoperative histopathological assessment. Currently, it is not clear whether these technologies improve the patient outcome directly; however, the review shows potential future implementations.

Background: Cerenkov Luminescence Imaging (CLI) is an emerging technology for intraoperative margin assessment. Previous research only evaluated radionuclide 18-Fluorine (¹⁸F); however, for future applications in prostate cancer, 68-Gallium (⁶⁸Ga) seems more suitable, given its higher positron energy. Theoretical calculations predict that ⁶⁸Ga should offer a higher signal-to-noise ratio than ¹⁸F; this is the first experimental confirmation. The aim of this study is to investigate the technical performance of CLI by comparing ⁶⁸Ga to ¹⁸F. Results: The linearity of the system, detection limit, spatial resolution, and uniformity were determined with the LightPath imaging system. All experiments were conducted with clinically relevant activity levels in vitro, using dedicated phantoms. For both radionuclides, a linear relationship between the activity concentration and detected light yield was observed (R² = 0.99). ⁶⁸Ga showed approximately 22 times more detectable Cerenkov signal compared to ¹⁸F. The detectable activity concentration after a 120 s exposure time and 2 × 2 binning of ¹⁸F was 23.7 kBq/mL and 1.2 kBq/mL for ⁶⁸Ga. The spatial resolution was 1.31 mm for ¹⁸F and 1.40 mm for ⁶⁸Ga. The coefficient of variance of the uniformity phantom was 0.07 for the central field of view. Conclusion: ⁶⁸Ga was superior over ¹⁸F in terms of light yield and minimal detection limit. However, as could be expected, the resolution was 0.1 mm less for ⁶⁸Ga. Given the clinical constraints of an acquisition time less than 120 s and a spatial resolution < 2 mm, CLI for intraoperative margin assessment using ⁶⁸Ga could be feasible.

Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) is a modern imaging tool used in the diagnosis of prostate cancer (PCa). Approximately 10% of patients who underwent PSMA PET/CT have a biopsy-proven, primary PCa without PSMA expression on PET/CT (non-PSMA_PET-expressing PCa), according to a recent systematic review[1]. However, the definition of non-PSMA_PET-expression in these studies was poorly defined and no immunohistochemical studies for confirmation of PSMA protein expression were performed. The aim of this retrospective study was to report the prevalence, characteristics, and immunohistochemical assessment of non-PSMA_PET-expressing hormone-sensitive PCa in a cohort of 362 patients who underwent PSMA PET/CT and robot-assisted radical prostatectomy (RARP).