Tracer-cocktail injections for combined pre- and intraoperative multimodal imaging of lymph nodes in a spontaneous mouse prostate tumor model

Abstract

Abstract. To improve surgical guidance toward prostate draining lymph nodes, we investigate the potential of intraoperative fluorescence imaging and combined pre-and intraoperative multimodality imaging approaches. Transgenic adenocarcinoma mouse prostate mice with spontaneous prostate tumors are injected intratumorally with: 1. a cocktail of patent blue (Pb) and indocyanine green (ICG); 2. a cocktail of albumin radiocolloids ( 99m TcNanoColl), Pb, and ICG; or 3. a cocktail of radiolabeled albumin ( 99m Tc-Vasculosis), Pb, and ICG. The distribution of these imaging agents over the lymph nodes (LNs) are studied at different time points after injection. We find that at 60-min postinjection, ICG significantly improves the detection of the LNs compared to Pb, 53 versus 7%, respectively. Moreover, a cocktail of ICG and 99m Tc-NanoColl improves the fluorescent detection rate to 86%, equalling that of the clinically applied 99m Tc-NanoColl. A similar overlap is observed in our initial clinical pilot data. Fluorescent detection of the LNs using a ICG with 99m Tc-Vasculosis gives similar results as "free" ICG (58%; 60 min). A 99m Tc-NanoColl, Pb, and cocktail ICG enriches the standard 99m Tc-NanoColl approach by adding optical detection of the sentinel lymph nodes. Furthermore, this approach improves fluorescent-based guidance and enables both accurate surgical planning and intraoperative detection, based on a single injection. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

Relationship Between Intraprostatic Tracer Deposits and Sentinel Lymph Node Mapping in Prostate Cancer Patients

“…The ICG-99m Tc-nanocolloid solution was prepared by adding 0.050 mL (0.250 mg ICG) of the ICGPulsion solution to 1 mL of 99m Tc-nanocolloid solution (pH 6-7). ICG-99m Tc-nanocolloid was formed via noncovalent interactions between ICG and albumin molecules (13)(14)(15). All procedures were performed under Kern Energie Wet (Nuclear Energy Law) using Dutch guidelines for good manufacturing practices and with the approval of the local pharmacist.…”

“…To achieve this, we developed a hybrid radiocolloid that can be visualized with a g-camera, SPECT/CT imaging, and near-infrared fluorescence imaging (13,14). This hybrid radiocolloid enabled us to link preoperative SN identification to intraoperative visualization of the SNs in patients with prostate carcinoma (15).…”

Comparing the Hybrid Fluorescent–Radioactive Tracer Indocyanine Green–99mTc-Nanocolloid with 99mTc-Nanocolloid for Sentinel Node Identification: A Validation Study Using Lymphoscintigraphy and SPECT/CT

“…Yet, because the signal penetration of fluorescent probes is limited by tissue attenuation, radioguidance to the general area of interest is still indispensable (23). To combine the beneficial properties of both modalities, a hybrid tracer comprising the fluorescent dye indocyanine green (ICG) and the human serum albumin-based radiocolloid 99m Tc-nanocolloid was developed (24,25). Recently, hybrid ICG-99m Tc-nanocolloid was introduced for laparoscopic and open sentinel node biopsies in patients with prostate cancer or head and neck melanoma (23,26,27).…”

Sentinel lymph node biopsy in renal malignancy: The past, present and future

“…The introduction and acknowledgement of NIRF as a tracer, has led to the potential for a hybrid tracer, combining the fluorescence of NIRF with the wellestablished pharmacokinetics and bio-distribution of radiocolloids such as technetium 99m. The use of a multimodal tracer was first studied in mice in 2011 [52] . Since then its use has been studied in prostate and melanoma with the finding that it is equally effective tracer with faster distribution than blue dye [53,54] .…”