Fluorescent Tracers for Imaging of Lymphatic Targets

Overview

Journal Front Pharmacol

Date 2022 Aug 8

PMID 35935839

Authors

P S Russell

R Velivolu

V E Maldonado Zimbron

J Hong

I Kavianinia

A J R Hickey

J A Windsor

A R J Phillips

Affiliations

Soon will be listed here.

Abstract

The lymphatic system continues to gain importance in a range of conditions, and therefore, imaging of lymphatic vessels is becoming more widespread for research, diagnosis, and treatment. Fluorescent lymphatic imaging offers advantages over other methods in that it is affordable, has higher resolution, and does not require radiation exposure. However, because the lymphatic system is a one-way drainage system, the successful delivery of fluorescent tracers to lymphatic vessels represents a unique challenge. Each fluorescent tracer used for lymphatic imaging has distinct characteristics, including size, shape, charge, weight, conjugates, excitation/emission wavelength, stability, and quantum yield. These characteristics in combination with the properties of the target tissue affect the uptake of the dye into lymphatic vessels and the fluorescence quality. Here, we review the characteristics of visible wavelength and near-infrared fluorescent tracers used for lymphatic imaging and describe the various techniques used to specifically target them to lymphatic vessels for high-quality lymphatic imaging in both clinical and pre-clinical applications. We also discuss potential areas of future research to improve the lymphatic fluorescent tracer design.

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References

Veikkola T, Jussila L, Makinen T, Karpanen T, Jeltsch M, Petrova T . Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice. EMBO J. 2001; 20(6):1223-31. PMC: 145532. DOI: 10.1093/emboj/20.6.1223. View

Parungo C, Soybel D, Colson Y, Kim S, Ohnishi S, Degrand A . Lymphatic drainage of the peritoneal space: a pattern dependent on bowel lymphatics. Ann Surg Oncol. 2006; 14(2):286-98. PMC: 2515477. DOI: 10.1245/s10434-006-9044-6. View

Ye T, Zhang H, Chen G, Shang L, Wang S . Fluorescent molecular imaging of metastatic lymph node using near-infrared emitting low molecular weight heparin modified nanoliposome based on enzyme-substrate interaction. Contrast Media Mol Imaging. 2016; 11(6):482-491. DOI: 10.1002/cmmi.1710. View

Gerli R, Solito R, Weber E, Agliano M . Specific adhesion molecules bind anchoring filaments and endothelial cells in human skin initial lymphatics. Lymphology. 2001; 33(4):148-57. View

Reed H, Wang L, Kahn M, Hancock W . Donor-host Lymphatic Anastomosis After Murine Lung Transplantation. Transplantation. 2019; 104(3):511-515. PMC: 7117875. DOI: 10.1097/TP.0000000000003041. View

Padera T, Kadambi A, Tomaso E, Carreira C, Brown E, Boucher Y . Lymphatic metastasis in the absence of functional intratumor lymphatics. Science. 2002; 296(5574):1883-6. DOI: 10.1126/science.1071420. View

Nune S, Gunda P, Majeti B, Thallapally P, Forrest M . Advances in lymphatic imaging and drug delivery. Adv Drug Deliv Rev. 2011; 63(10-11):876-85. PMC: 3164439. DOI: 10.1016/j.addr.2011.05.020. View

Samdal Steinskog E, Sagstad S, Wagner M, Karlsen T, Yang N, Markhus C . Impaired lymphatic function accelerates cancer growth. Oncotarget. 2016; 7(29):45789-45802. PMC: 5216761. DOI: 10.18632/oncotarget.9953. View

Gashev A, Nagai T, Bridenbaugh E . Indocyanine green and lymphatic imaging: current problems. Lymphat Res Biol. 2010; 8(2):127-30. PMC: 2939850. DOI: 10.1089/lrb.2010.0005. View

10.

Guo W, Zhang L, Ji J, Gao W, Liu J, Tong M . Evaluation of the benefit of using blue dye in addition to indocyanine green fluorescence for sentinel lymph node biopsy in patients with breast cancer. World J Surg Oncol. 2014; 12:290. PMC: 4182872. DOI: 10.1186/1477-7819-12-290. View

11.

Kaminskas L, Kota J, McLeod V, Kelly B, Karellas P, Porter C . PEGylation of polylysine dendrimers improves absorption and lymphatic targeting following SC administration in rats. J Control Release. 2009; 140(2):108-16. DOI: 10.1016/j.jconrel.2009.08.005. View

12.

Leu A, Berk D, Lymboussaki A, Alitalo K, Jain R . Absence of functional lymphatics within a murine sarcoma: a molecular and functional evaluation. Cancer Res. 2000; 60(16):4324-7. View

13.

Polomska A, Proulx S . Imaging technology of the lymphatic system. Adv Drug Deliv Rev. 2020; 170:294-311. DOI: 10.1016/j.addr.2020.08.013. View

14.

Wiig H, Swartz M . Interstitial fluid and lymph formation and transport: physiological regulation and roles in inflammation and cancer. Physiol Rev. 2012; 92(3):1005-60. DOI: 10.1152/physrev.00037.2011. View

15.

Castorena-Gonzalez J, Zawieja S, Li M, Srinivasan R, Simon A, De Wit C . Mechanisms of Connexin-Related Lymphedema. Circ Res. 2018; 123(8):964-985. PMC: 6771293. DOI: 10.1161/CIRCRESAHA.117.312576. View

16.

Brouillard P, Witte M, Erickson R, Damstra R, Becker C, Quere I . Primary lymphoedema. Nat Rev Dis Primers. 2021; 7(1):77. DOI: 10.1038/s41572-021-00309-7. View

17.

Yang Y, Zhang F . Molecular fluorophores for in vivo bioimaging in the second near-infrared window. Eur J Nucl Med Mol Imaging. 2022; 49(9):3226-3246. DOI: 10.1007/s00259-022-05688-x. View

18.

Ikeda I, Tomari Y, Sugano M, Watanabe S, Nagata J . Lymphatic absorption of structured glycerolipids containing medium-chain fatty acids and linoleic acid, and their effect on cholesterol absorption in rats. Lipids. 1991; 26(5):369-73. DOI: 10.1007/BF02537201. View

19.

Kitai T, Inomoto T, Miwa M, Shikayama T . Fluorescence navigation with indocyanine green for detecting sentinel lymph nodes in breast cancer. Breast Cancer. 2005; 12(3):211-5. DOI: 10.2325/jbcs.12.211. View

20.

Ansari S, Satar R, Jafri M, Rasool M, Ahmad W, Zaidi S . Role of Nanodiamonds in Drug Delivery and Stem Cell Therapy. Iran J Biotechnol. 2017; 14(3):130-141. PMC: 5492243. DOI: 10.15171/ijb.1320. View