Dataset Information

Structure-inherent targeting of near-infrared fluorophores for parathyroid and thyroid gland imaging.

ABSTRACT: The typical method for creating targeted contrast agents requires covalent conjugation of separate targeting and fluorophore domains. In this study, we demonstrate that it is possible to create near-infrared (NIR) fluorophores with different tissue specificities driven by their inherent chemical structures. Thus, a single compact molecule performs both targeting and imaging. We use this strategy to solve a major problem in head and neck surgery: the identification and preservation of parathyroid and thyroid glands. We synthesized 700-nm and 800-nm halogenated fluorophores that show high uptake into these glands after a single intravenous (IV) injection of 0.06 mg kg(-1) in a pig. By using a dual-channel NIR imaging system, we observed-in real time and with high sensitivity-the unambiguous distinction of parathyroid and thyroid glands simultaneously in the context of blood and surrounding soft tissue. This novel technology lays a foundation for performing head and neck surgery with increased precision and efficiency along with potentially lower morbidity, and it provides a general strategy for developing targeted NIR fluorophores.

SUBMITTER: Hyun H

PROVIDER: S-EPMC4319985 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Structure-inherent targeting of near-infrared fluorophores for parathyroid and thyroid gland imaging.

Hyun Hoon H Park Min Ho MH Owens Eric A EA Wada Hideyuki H Henary Maged M Handgraaf Henricus J M HJ Vahrmeijer Alexander L AL Frangioni John V JV Choi Hak Soo HS

Nature medicine 20150105 2

The typical method for creating targeted contrast agents requires covalent conjugation of separate targeting and fluorophore domains. In this study, we demonstrate that it is possible to create near-infrared (NIR) fluorophores with different tissue specificities driven by their inherent chemical structures. Thus, a single compact molecule performs both targeting and imaging. We use this strategy to solve a major problem in head and neck surgery: the identification and preservation of parathyroid ...[more]

PMID: 25559343

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Project description:Contrast-free autofluorescence (AF) of the parathyroid glands (PTGs) and thyroid tissue occurs in the near-infrared (NIR) spectrum on excitation by light in the upper range of the visible spectrum or lower NIR spectrum. In vivo, PTGs autofluoresce more brightly than thyroid (by a factor of 2-20 times) and appear as a bright spot against surrounding thyroid, muscle or fat on a processed image which is generated in real-time. NIR-AF of PTGs was first described in 2009 although NIR-AF had previously been used in several other clinical applications. Since then there has been a great amount of interest in the use of NIR-AF in thyroid and parathyroid surgery with over 25 published reports of the utilisation of both self-built and proprietary NIR-AF devices in neck endocrine surgery. All of these reports have confirmed the feasibility of NIR-AF intraoperatively and its ability to detect PTGs, although the reported accuracy varies from 90-100%. Reports of the effect of NIR-AF on relevant clinical endpoints i.e., post-operative hypoparathyroidism in thyroidectomy and persistent disease in parathyroidectomy are however scant. There has been one multicentre clinical trial of NIR-AF in thyroidectomy but this did not report clinical outcomes and two single-centre, non-randomised studies which did report post-operative hypoparathyroidism but with differing results: one showing no benefit in 106 NIR-AF vs. 163 controls and one, a reduction of early hypocalcaemia from 20% to 5% in 93 NIR-AF patients vs. 420 controls. There were only 2 cases of permanent hypoparathyroidism across both studies and therefore no significant observable difference in this key outcome variable. In parathyroidectomy, possible variability of the AF signal due to composition of a PTG adenoma, secondary/tertiary disease and MEN1 as well as depth-penetration preventing detection of sub-surface PTGs would imply that NIR-AF in its current form is not well-placed to improve cure-rates in hyperparathyroidism, which may already be as high as 98%. Thus far, no study has addressed this. Despite the promising results of NIR-AF, the absence of data demonstrating an improvement in outcomes and the cost of its use currently limit its use in routine clinical practice, especially in a publicly funded healthcare system with budgetary constraints. However, it can be utilised in research settings and this should be undertaken within the context of well-designed and conducted randomised, multi-centre, appropriately powered studies, which will assist in establishing its role in neck endocrine surgery.

Dataset Information

Structure-inherent targeting of near-infrared fluorophores for parathyroid and thyroid gland imaging.

Publications

Structure-inherent targeting of near-infrared fluorophores for parathyroid and thyroid gland imaging.

Similar Datasets

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