Abstract
PurposeAt present, the only approved fluorescent tracer for clinical near-infrared fluorescence-guided sentinel node (SN) detection is indocyanine green (ICG), but the use of this tracer is limited due to its poor retention in the SN resulting in the detection of higher tier nodes. We describe the development and characterization of a next-generation fluorescent tracer, nanocolloidal albumin-IRDye 800CW that has optimal properties for clinical SN detectionMethodsThe fluorescent dye IRDye 800CW was covalently coupled to colloidal human serum albumin (HSA) particles present in the labelling kit Nanocoll in a manner compliant with current Good Manufacturing Practice. Characterization of nanocolloidal albumin-IRDye 800CW included determination of conjugation efficiency, purity, stability and particle size. Quantum yield was determined in serum and compared to that of ICG. For in vivo evaluation a lymphogenic metastatic tumour model in rabbits was used. Fluorescence imaging was performed directly after peritumoral injection of nanocolloidal albumin-IRDye 800CW or the reference ICG/HSA (i.e. ICG mixed with HSA), and was repeated after 24 h, after which fluorescent lymph nodes were excised.ResultsConjugation of IRDye 800CW to nanocolloidal albumin was always about 50% efficient and resulted in a stable and pure product without affecting the particle size of the nanocolloidal albumin. The quantum yield of nanocolloidal albumin-IRDye 800CW was similar to that of ICG. In vivo evaluation revealed noninvasive detection of the SN within 5 min of injection of either nanocolloidal albumin-IRDye 800CW or ICG/HSA. No decrease in the fluorescence signal from SN was observed 24 h after injection of the nanocolloidal albumin-IRDye 800CW, while a strong decrease or complete disappearance of the fluorescence signal was seen 24 h after injection of ICG/HSA. Fluorescence-guided SN biopsy was very easy.ConclusionNanocolloidal albumin-IRDye 800CW is a promising fluorescent tracer with optimal kinetic features for SN detection.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-012-2080-5) contains supplementary material, which is available to authorized users.
Highlights
The sentinel node (SN) procedure is a diagnostic staging procedure, which is applied in a variety of tumour types, including head and neck squamous cell carcinoma (HNSCC) [1, 2]
Coupling of IRDye 800CW to nanocolloidal albumin as well as native human serum albumin (HSA) resulted in a conjugation yield of about
On average 1.4 IRDye 800CW molecules were coupled per HSA molecule in the nanocolloidal albumin particles
Summary
The sentinel node (SN) procedure is a diagnostic staging procedure, which is applied in a variety of tumour types, including head and neck squamous cell carcinoma (HNSCC) [1, 2]. To pinpoint the exact localization of the SN, so that the duration and extent of surgical exploration is minimized, intraoperative gamma probe-guided detection and blue dye lymphography are used. The gamma probe is used to guide the surgeon to the SN, which still contains sufficient amounts of radiocolloid at the time of surgery. The limitation of the gamma probe, is the lack of real-time visualization of the SN and information about SN depth. As a result of high radioactivity arising from the injection site, detection of a SN close to the tumour may be difficult. Blue dye is injected in the same way as the radiocolloid, just before surgery, allowing real-time lymphatic mapping. Real-time detection of this blue staining is only possible if there is no overlying tissue. The use of blue dye is of limited added value in the head and neck area [4]
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