European Nuclear Medicine Guide
iNM, especially when it is combined with hybrid pharmaceuticals and technologically complex interventions is considered to be a transformative force in oncological care. Over the years routine procedures such as SLN biopsy have been refined substantially. This has enabled more precise target localization, reduced surgical invasiveness, and has resulted in improved patient outcome [92-94].
These advances are driven by a combination of chemistry, engineering, and physics. The technical innovations that made it possible to support a variety of interventional settings and scale the implementation receptor-targeted approaches. Critical, however, is that technology developers hold expert knowledge of the specific aspect of the procedure wherein additional guidance is needed, as well as the practical constraints faced in real-life [95-96].
By creating tethered gamma- (and beta) detectors, so-called drop-in probes, it has become possible to match RGS to the dexterity of steerable (robotic) instruments, thereby improving ergonomics. Studies indicate that the drop-in detectors help complement the robot-embodied fluorescence-endoscope output with “fingertip molecular imaging”, allowing for more accurate SLN detection in the pelvis [97-98]. This approach aligns visual surgical perception with the robot-tissue interaction [99-101].
For example, the drop-in gamma probe has seen implementation during (hybrid) SLN biopsy in urology and gynecology and that has been used to support PSMA-receptor targeted surgery (primary and salvage) [45, 102, 103]. Comparison between SLN and receptor targeting surgery indicate that: 1) The signal intensities seen at preoperative imaging are predictive for the intensities identified during surgery, whereby signal intensities are about one order of magnitude higher for SLN applications, and 2) Decision making is highly dependent on the ability to distinguish a target from its surroundings, whereby a signal to background > 2 appears to be desirable [104]. Uniquely, video-tracking of the drop-in probe position within the abdominal space helps convert the probe readouts into a tomographic image that can now be used to augment the endoscopic view [105]. This example indicates how essentially decades of system engineering can help push the field forward. Similar cases can be made for beta-probe guided surgery. This indicates that the maturation of the field is increasingly creating new opportunities that align with the increasing robotization and digitization of interventions [86, 106].
De-escalation in breast cancer surgery aims to minimize the extent of surgical intervention while maintaining oncological safety. RGS has played a pivotal role in this paradigm shift, particularly in the context of SLN biopsy and breast-conserving surgery. Studies have demonstrated that RGS-guided SLN biopsy can accurately stage axillary lymph nodes, avoiding unnecessary axillary lymph node dissection (ALND) in patients with early-stage breast cancer.
ALND remains standard of care for patients with clinically node-negative breast cancer with positive SLNs who do not meet the eligibility criteria of trials, such as ACOSOG Z0011, IBCSG 23-01 and EORTC AMAROS and for patients with clinically node-positive BC in the upfront surgery setting and with residual nodal disease after primary systemic therapy (PST). Those trials led to much variation in routine clinical practice and have created challenges in management for certain clinical scenarios such as axillary treatment after systemic therapy. For example, the only way to omit ALND in patients with clinically node positive breast cancer to date is to perform primary systemic therapy and determine nodal pathological complete response with limited axillary surgery.
Marking the positive node with a radioactive seed and selective removal without SLN biopsy, a procedure called MARI, reduced the false negative rate to 7% and showed low rates of axillary recurrence. The combination of SLNB with imaging-guided localization and removal of the biopsied node (known as targeted axillary dissection or TAD), can reduce the false negative rate to under 4%. Several multicenter studies, such as AXSANA (EUBREAST-03) and MINIMAX, are currently evaluating the optimal staging technique and long-term outcomes after omission of ALND in this population [107].
Intraoperative margin assessment is crucial in oncological surgeries to ensure complete tumor resection and minimize the need for reoperations. To support this, several technologies have been developed allowing for back-table specimen imaging to determine margin status of the removed tumor specimens. While Cerenkov imaging has been studied for this for a longer time, intraoperative PET/CT specimen scanners have experienced an increased interest. These are currently explored across various tumor types.
In prostate cancer surgeries, some studies demonstrated the feasibility of procedures guided with [68Ga]Ga-PSMA or [18F]F-PSMA-1007. Here, imaging of the resected specimens indicated feasibility to image negative and positive (i.e., close <1 mm) surgical margins of the primary tumor as well as positive lymph nodes, indicating initial agreement with histopathology. Current studies also indicate a strong correlation between specimen PET/CT and conventional PET/CT in detecting suspicious tracer foci. This intraoperative imaging approach provided information, potentially improving oncological outcomes by guiding surgical decisions. Next to prostate cancer, these PET/CT specimen scanners have also shown value in early-stage breast cancer surgery, using the tracer FDG for RGS [77, 78, 108].
Interestingly, successful specimen imaging has recently also been demonstrated using PSMA-targeted SPECT tracers in primary prostate cancer, by combining the freehand SPECT technology with LiDAR scanning [43]. This would allow for a relatively cheap analogy that could be used in SPECT-based RGS.