First-in-human evaluation of a hybrid modality that allows combined radio- and (near-infrared) fluorescence tracing during surgery

PurposeThe clinical introduction of the hybrid tracer indocyanine green (ICG)-99mTc-nanocolloid, composed of a radioactive and a near-infrared (NIR) fluorescence component, has created the need for surgical (imaging) modalities that allow for simultaneous detection of both signals. This study describes the first-in-human use of a prototype opto-nuclear probe during sentinel node (SN) biopsy using ICG-99mTc-nanocolloid.MethodsTo allow for fluorescence tracing, a derivative of the conventional gamma probe technology was generated in which two optical fibers were integrated to allow for excitation (785 nm) and emission signal collection (> 810 nm). The ability of this opto-nuclear probe to detect the fluorescence signal of the hybrid tracer ICG-99mTc-nanocolloid was firstly determined ex vivo in (non)SNs samples obtained from 41 patients who underwent hybrid tracer-based SN biopsy in the head and neck or urogenital area. In an in vivo proof-of-concept study in nine of these 41 patients, SNs were localized using combined gamma and fluorescence tracing with the opto-nuclear probe. Fluorescence tracing was performed in a similar manner as gamma tracing and under ambient light conditions.ResultsEx vivo, the gamma tracing option of the opto-nuclear probe correctly identified the SN in all 150 evaluated (non)SN samples. Ex vivo fluorescence tracing in the low-sensitivity mode correctly identified 71.7 % of the samples. This increased to 98.9 % when fluorescence tracing was performed in the high-sensitivity mode. In vivo fluorescence tracing (high-sensitivity mode) accurately identified the SNs in all nine patients (20 SNs evaluated; 100 %).ConclusionThis study demonstrates the first-in-human evaluation of a hybrid modality capable of detecting both gamma and fluorescence signals during a surgical procedure. Fluorescence tracing could be performed in ambient light.