Intraoperative Laparoscopic Fluorescence Guidance to the Sentinel Lymph Node in Prostate Cancer Patients: Clinical Proof of Concept of an Integrated Functional Imaging Approach Using a Multimodal Tracer

Abstract

Background

Integration of molecular imaging and in particular intraoperative image guidance is expected to improve the surgical accuracy of laparoscopic lymph node (LN) dissection.

Objective

To show the applicability of combining preoperative, intraoperative, and postoperative sentinel node imaging using an integrated diagnostic approach based on an imaging agent that is both radioactive and fluorescent.

Design, setting, and participants

Before surgery, multimodal indocyanine green (ICG)-^99mTc-NanoColl was injected into the prostate. Subsequent lymphoscintigraphy and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging of pelvic nodes was performed to determine the location of the sentinel lymph nodes (SLNs) preoperatively. During the surgical procedure a fluorescence laparoscope, optimized for detection in the near infrared range, was used to visualize the nodes identified on SPECT/CT. Eleven patients scheduled for robot-assisted laparoscopic prostatectomy (RALP) with an increased risk of nodal metastasis, based on Memorial Sloan-Kettering Cancer Center/Kattan nomogram estimation, participated in a pilot assessment (N09IGF).

Surgical procedure

Patients underwent RALP with LN dissection for prostate cancer.

Measurements

Radioactive and fluorescent signals were monitored using different modalities, and the correlation between the two types of signals was studied. The location of preoperatively detected SLNs was documented.

Results and limitations

Preoperatively, SLNs were identified by SPECT/CT, and the multimodal nature of the imaging agent also enabled intraoperative detection via fluorescence imaging. Fluorescence particularly improved surgical guidance in areas with a high radioactive background signal such as the injection site. Ex vivo analysis revealed a strong correlation between the radioactive and fluorescent content in the excised LNs. Fluorescence detection is limited by the severe tissue attenuation of the signal. Therefore, radio guidance to the areas of interest is still desirable.

Conclusions

Initial data indicate that multimodal ICG-^99mTc-NanoColloid, in combination with a laparoscopic fluorescence laparoscope, can be used to facilitate and optimize dissection of SLNs during RALP procedures.

Introduction

Functional (optical) imaging holds great promise to supplement surgeons’ eyes and improve surgical outcome [1], [2]. One very practical clinical application where imaging can help guide the surgical intervention is the identification of lymph nodes (LNs) draining directly from the tumor (sentinel lymph nodes [SLNs]). Functional imaging of SLNs depends on lymphatic migration and nodal accumulation of the imaging agents [3], [4]. Such imaging agents can be relatively simple in design, improving their translational character. For this reason SLN imaging can act as the first clinical precedent for the introduction of new surgical guidance technologies.

The identification of SLNs is common practice in breast cancer and melanoma, for example [5], [6]. Although the role of SLN dissection in prostate cancer is still under debate, sentinel lymphadenectomy has been shown to be accurate for LN staging [7], [8]. SLNs outside the area of extended pelvic lymphadenectomy have also been described, underlining the need to document lymphatic drainage pathways for each patient [9]. We reasoned that a more accurate removal of prostate cancer– associated SLNs would help identify the value of nodal resection in prostate cancer patients and might provide better staging. Preoperative single-photon emission computed tomography/computed tomography (SPECT/CT) imaging provides useful anatomic information regarding the location of the SLNs and allows for the identification of SLNs that lie beyond the standard dissection margins [10]. In addition to their diagnostic purposes, these preoperative images can act as a (rough) guide during surgery.

Prostatectomy for cancer has shifted from the open approach toward less invasive laparoscopic and robot-assisted techniques [11]. Although advances in surgical instrumentation have been made, fluorescence-guided (robotic) surgery is still in its infancy. The next step in the technical evolution of surgical interventions is the integration of optical imaging modalities that specifically visualize the areas of interest. Most clinical studies regarding optical surgical guidance to the SLNs have focused on the use of a fluorescent imaging agent, for example, indocyanine green (ICG) [12], [13]. However, this rapidly migrating imaging agent has to be administered intraoperatively, and its pharmacokinetics and biodistribution cannot be monitored accurately. To circumvent these problems, we developed a hybrid multimodal radiocolloid (ICG-^99mTc-NanoColl; Fig. 1A) that is both radioactive and fluorescent. The principal advantage of this multimodal tracer is that in addition to its optical properties, it retains the well-established functional properties of ^99mTc-NanoColl, including accumulation in the SLNs [14], [15].

Here we present the first human studies of an integrated method that enables preoperative planning of the SLN procedure and allows for intraoperative visualization of the SLNs. For this study we used a hybrid radiocolloid that is detectable by gamma camera, SPECT/CT, and near infrared (NIR) fluorescence imaging.