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Nanocolloidal albumin-IRDye 800CW: a near-infrared fluorescent tracer with optimal retention in the sentinel lymph node.

Heuveling DA, Visser GW, de Groot M, de Boer JF, Baclayon M, Roos WH, Wuite GJ, Leemans CR, de Bree R, van Dongen GA - Eur. J. Nucl. Med. Mol. Imaging (2012)

Bottom Line: Conjugation 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.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.Nanocolloidal albumin-IRDye 800CW is a promising fluorescent tracer with optimal kinetic features for SN detection.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands.

ABSTRACT

Purpose: At 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 detection.

Methods: The 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.

Results: Conjugation 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.

Conclusion: Nanocolloidal albumin-IRDye 800CW is a promising fluorescent tracer with optimal kinetic features for SN detection.

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Noninvasive real-time NIR fluorescence detection of a fluorescence-labelled lymph node in the neck of a rabbit. a Preoperative image after administration of nanocolloidal albumin-IRDye800CW (a angle of mandible, arrow lymph node, N neck). b Intraoperative image after preparation of a skin flap (a angle of mandible). c, d Removal of the lymph node (c) after which no fluorescence signal is detectable (d) indicating complete removal of fluorescence-containing tissues. Note the high contrast between the fluorescent lymph node and the surrounding tissue. Exposure time in all images was 200 ms
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Fig4: Noninvasive real-time NIR fluorescence detection of a fluorescence-labelled lymph node in the neck of a rabbit. a Preoperative image after administration of nanocolloidal albumin-IRDye800CW (a angle of mandible, arrow lymph node, N neck). b Intraoperative image after preparation of a skin flap (a angle of mandible). c, d Removal of the lymph node (c) after which no fluorescence signal is detectable (d) indicating complete removal of fluorescence-containing tissues. Note the high contrast between the fluorescent lymph node and the surrounding tissue. Exposure time in all images was 200 ms

Mentions: In all experiments draining lymph nodes (parotid lymph node and caudal mandibular lymph node) became visible within 5 min by noninvasive imaging of either nanocolloidal albumin-IRDye 800CW (Fig. 2b) or ICG/HSA (Fig. 2d). After 24 h, noninvasive NIR fluorescence imaging was still able to identify the same 12 draining lymph nodes (parotid and caudal mandibular lymph nodes) in six of six tumours (100%) injected with nanocolloidal albumin-IRDye 800CW, without a decrease in signal intensity and without an increase in background fluorescence (Fig. 2c). However, after 24 h, SNs identified with ICG/HSA during early imaging showed an observable decrease in fluorescence signal, while in 4 of 12 lymph nodes (33%) the fluorescence signal was completely absent (Fig. 2e). Even after open surgery with adjustment of the Fluobeam camera settings (e.g. highest exposure time), these lymph nodes were not detectable. Once a fluorescence signal was detected, it was easy to excise the SN because of the clear delineation of the fluorescence-labelled lymph nodes and the high target-to-background ratio (Fig. 4).Fig. 4


Nanocolloidal albumin-IRDye 800CW: a near-infrared fluorescent tracer with optimal retention in the sentinel lymph node.

Heuveling DA, Visser GW, de Groot M, de Boer JF, Baclayon M, Roos WH, Wuite GJ, Leemans CR, de Bree R, van Dongen GA - Eur. J. Nucl. Med. Mol. Imaging (2012)

Noninvasive real-time NIR fluorescence detection of a fluorescence-labelled lymph node in the neck of a rabbit. a Preoperative image after administration of nanocolloidal albumin-IRDye800CW (a angle of mandible, arrow lymph node, N neck). b Intraoperative image after preparation of a skin flap (a angle of mandible). c, d Removal of the lymph node (c) after which no fluorescence signal is detectable (d) indicating complete removal of fluorescence-containing tissues. Note the high contrast between the fluorescent lymph node and the surrounding tissue. Exposure time in all images was 200 ms
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3369133&req=5

Fig4: Noninvasive real-time NIR fluorescence detection of a fluorescence-labelled lymph node in the neck of a rabbit. a Preoperative image after administration of nanocolloidal albumin-IRDye800CW (a angle of mandible, arrow lymph node, N neck). b Intraoperative image after preparation of a skin flap (a angle of mandible). c, d Removal of the lymph node (c) after which no fluorescence signal is detectable (d) indicating complete removal of fluorescence-containing tissues. Note the high contrast between the fluorescent lymph node and the surrounding tissue. Exposure time in all images was 200 ms
Mentions: In all experiments draining lymph nodes (parotid lymph node and caudal mandibular lymph node) became visible within 5 min by noninvasive imaging of either nanocolloidal albumin-IRDye 800CW (Fig. 2b) or ICG/HSA (Fig. 2d). After 24 h, noninvasive NIR fluorescence imaging was still able to identify the same 12 draining lymph nodes (parotid and caudal mandibular lymph nodes) in six of six tumours (100%) injected with nanocolloidal albumin-IRDye 800CW, without a decrease in signal intensity and without an increase in background fluorescence (Fig. 2c). However, after 24 h, SNs identified with ICG/HSA during early imaging showed an observable decrease in fluorescence signal, while in 4 of 12 lymph nodes (33%) the fluorescence signal was completely absent (Fig. 2e). Even after open surgery with adjustment of the Fluobeam camera settings (e.g. highest exposure time), these lymph nodes were not detectable. Once a fluorescence signal was detected, it was easy to excise the SN because of the clear delineation of the fluorescence-labelled lymph nodes and the high target-to-background ratio (Fig. 4).Fig. 4

Bottom Line: Conjugation 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.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.Nanocolloidal albumin-IRDye 800CW is a promising fluorescent tracer with optimal kinetic features for SN detection.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands.

ABSTRACT

Purpose: At 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 detection.

Methods: The 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.

Results: Conjugation 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.

Conclusion: Nanocolloidal albumin-IRDye 800CW is a promising fluorescent tracer with optimal kinetic features for SN detection.

Show MeSH
Related in: MedlinePlus