A DROP-IN beta probe for robot-assisted 68Ga-PSMA radioguided surgery: first ex vivo technology evaluation using prostate cancer specimens

Abstract

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 68 Ga-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 68 Ga-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. 68 Ga-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.

The current status and future prospects for molecular imaging-guided precision surgery

“…Following the design of laparoscopic surgical instruments there is a trend to move from ‘rigid’ laparoscopic modalities to ‘steerable’ ones. Examples are the use of tethered drop-in detectors for US [ 153 , 154 ], gamma-tracing [ 155 ], beta-tracing [ 156 ].…”

Robot-assisted prostate-specific membrane antigen-radioguided surgery in primary diagnosed prostate cancer

“…Another consideration is the use of alternative PSMA-targeting tracers that do not suffer from deeper lying background signals (21). In a recent series potential mitigation of such interference was explored (ex-vivo) by employing 68 Ga-PSMA-11 as a radiotracer, with a novel drop-in beta probe utilising the limited tissue penetration exhibited by beta particle emission (22). Their findings demonstrated high beta radiation attenuation when >1.5 mm of normal tissue separated probe from tumour.…”

How molecular imaging will enable robotic precision surgery

“…This still leaves a lot of room to investigate the value of alternative approaches using, for example, PET-based signals (i.e., beta plus or high-energy gamma emissions), beta minus emissions, or SPION detection, as well as alternative hybrid approaches with Cerenkov, multispectral/multiwavelength fluorescence, MSOT, and Raman spectrometry [16]. To make these imaging modalities, which often find their origin in open surgery, compatible with (laparoscopic) robotic surgery, we observe trends such as miniaturization, tethering, and positional tracking (e.g., [33,78,105,222]). A likely future scenario is that more image-guidance modalities will eventually be wholly integrated into the robotic platform as done for fluorescence imaging.…”

“…Recent studies indicate the DROP-IN also facilitates receptor-targeted surgery in the robotic setting (e.g., PSMA RGS [28]). These DROP-IN concepts applied to gamma probes in robotic surgery can be readily transferred to beta-probes [105] and as such allow for intraoperative detection of typical "PET-isotopes" (beta plus, e.g., 18 F or 68 Ga) and even opens the door for "therapeutic isotopes" (beta minus, e.g., 90…”