Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
European Journal of Nuclear Medicine and Molecular Imaging
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 8/2022

02.02.2022 | Original Article

Galectin expression detected by 68Ga-galectracer PET as a predictive biomarker of radiotherapy resistance

verfasst von: Dehua Lu, Haoyi Zhou, Nan Li, Yanpu Wang, Ting Zhang, Fei Wang, Ning Liu, Hua Zhu, Jinming Zhang, Zhi Yang, Zhaofei Liu

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 8/2022

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Hypoxia is a hallmark of solid tumors that is related to radiotherapy resistance. As galectin members, such as galectin-1 and galectin-3, are associated with tumor hypoxia, herein we aimed to investigate whether positron emission tomography (PET) imaging of galectin expression can be employed to effectively pinpoint tumor hypoxia, and to predict radiotherapy resistance.

Methods

We synthesized a galectin-targeting radiotracer, designated 68Ga-galectracer, by radiolabeling a thiodigalactoside derivative. The properties of 68Ga-galectracer for PET imaging of tumor hypoxia were characterized in three tumor hypoxia mouse models. Additionally, preliminary PET/CT was performed in two patients with lung cancer to investigate the potential application of 68Ga-galectracer for clinical imaging.

Results

High-contrast imaging was achieved in the murine acute hypoxia tumor model, A549 natural hypoxia model, and sorafenib treatment-induced hypoxic 4T1 tumor model by PET using 68Ga-galectracer. In fact, 68Ga-galectracer exhibited superior hypoxia detection to that of 18F-misonidazole in the 4T1 tumors. Moreover, tumors with high galectin expression levels, as detected by 68Ga-galectracer PET, exhibited significantly lower responses to subsequent radiotherapy compared to those with low galectin expression levels. In patients with lung cancer, PET imaging using 68Ga-galectracer provided data that were complementary to that of the glucose metabolic PET radiotracer 18F-fluorodeoxyglucose.

Conclusion

68Ga-galectracer is a promising radiotracer for PET-based imaging of tumor hypoxia in vivo. Thus, hypoxia PET with 68Ga-galectracer could provide a noninvasive approach to proactively predict radiotherapy efficacy.

Trial registration

Chictr.org.cn (ChiCTR2000029522). Registered 03 February 2020.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Miller KD, Nogueira L, Mariotto AB, Rowland JH, Yabroff KR, Alfano CM, et al. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin. 2019;69:363–85.PubMedCrossRef
2.
3.
Rockwell S, Dobrucki IT, Kim EY, Marrison ST, Vu VT. Hypoxia and radiation therapy: past history, ongoing research, and future promise. Curr Mol Med. 2009;9:442–58.PubMedPubMedCentralCrossRef
4.
5.
Horsman MR, Mortensen LS, Petersen JB, Busk M, Overgaard J. Imaging hypoxia to improve radiotherapy outcome. Nat Rev Clin Oncol. 2012;9:674–87.PubMedCrossRef
6.
7.
Sun X, Niu G, Chan N, Shen B, Chen X. Tumor hypoxia imaging. Mol Imaging Biol. 2011;13:399–410.PubMedCrossRef
8.
Stieb S, Eleftheriou A, Warnock G, Guckenberger M, Riesterer O. Longitudinal PET imaging of tumor hypoxia during the course of radiotherapy. Eur J Nucl Med Mol Imaging. 2018;45:2201–17.PubMedCrossRef
9.
Strauss HW, Nunn A, Linder K. Nitroimidazoles for imaging hypoxic myocardium. J Nucl Cardiol. 1995;2:437–45.PubMedCrossRef
10.
Barondes SH, Cooper DN, Gitt MA, Leffler H. Galectins. Structure and function of a large family of animal lectins. J Biol Chem. 1994;269:20807–10.
11.
Ito K, Stannard K, Gabutero E, Clark AM, Neo SY, Onturk S, et al. Galectin-1 as a potent target for cancer therapy: role in the tumor microenvironment. Cancer Metastasis Rev. 2012;31:763–78.PubMedCrossRef
12.
13.
Gu X, Meng H, Wang J, Wang R, Cao M, Liu S, et al. Hypoxia contributes to galectin-3 expression in renal carcinoma cells. Eur J Pharmacol. 2021;890:173637.
14.
Kuo P, Bratman SV, Shultz DB, von Eyben R, Chan C, Wang Z, et al. Galectin-1 mediates radiation-related lymphopenia and attenuates NSCLC radiation response. Clin Cancer Res. 2014;20:5558–69.PubMedPubMedCentralCrossRef
15.
Lai J, Lu D, Zhang C, Zhu H, Gao L, Wang Y, et al. Noninvasive small-animal imaging of galectin-1 upregulation for predicting tumor resistance to radiotherapy. Biomaterials. 2018;158:1–9.PubMedCrossRef
16.
Carlucci G, Ippisch R, Slavik R, Mishoe A, Blecha J, Zhu S. 68Ga-PSMA-11 NDA approval: a novel and successful academic partnership. J Nucl Med. 2021;62:149–55.PubMedPubMedCentralCrossRef
17.
Gourd E. New radiotracer shows impressive diagnostic potential. Lancet Oncol. 2019;20:e353.
18.
Zhang H, Laaf D, Elling L, Pieters RJ. Thiodigalactoside–bovine serum albumin conjugates as high-potency inhibitors of galectin-3: an outstanding example of multivalent presentation of small molecule inhibitors. Bioconjug Chem. 2018;29:1266–75.PubMedPubMedCentralCrossRef
19.
van Hattum H, Branderhorst HM, Moret EE, Nilsson UJ, Leffler H, Pieters RJ. Tuning the preference of thiodigalactoside- and lactosamine-based ligands to galectin-3 over galectin-1. J Med Chem. 2013;56:1350–4.PubMedCrossRef
20.
Zhao Y, Zhang T, Wang Y, Lu D, Du J, Feng X, et al. ICAM-1 orchestrates the abscopal effect of tumor radiotherapy. Proc Natl Acad Sci U S A. 2021;118:e2010333118.
21.
Jin CS, Lovell JF, Chen J, Zheng G. Ablation of hypoxic tumors with dose-equivalent photothermal, but not photodynamic, therapy using a nanostructured porphyrin assembly. ACS Nano. 2013;7:2541–50.PubMedPubMedCentralCrossRef
22.
Feng X, Wang Y, Lu D, Xu X, Zhou X, Zhang H, et al. Clinical translation of a 68Ga-labeled integrin αvβ6-targeting cyclic radiotracer for PET imaging of pancreatic cancer. J Nucl Med. 2020;61:1461–7.PubMedPubMedCentralCrossRef
23.
Rabinovich GA, Vidal M. Galectins and microenvironmental niches during hematopoiesis. Curr Opin Hematol. 2011;18:443–51.PubMedCrossRef
24.
Gilson RC, Gunasinghe SD, Johannes L, Gaus K. Galectin-3 modulation of T-cell activation: mechanisms of membrane remodelling. Prog Lipid Res. 2019;76:101010.
25.
Bhat R, Belardi B, Mori H, Kuo P, Tam A, Hines WC, et al. Nuclear repartitioning of galectin-1 by an extracellular glycan switch regulates mammary morphogenesis. Proc Natl Acad Sci U S A. 2016;113:E4820–7.PubMedPubMedCentralCrossRef
26.
D’Alessandria C, Braesch-Andersen S, Bejo K, Reder S, Blechert B, Schwaiger M, et al. Noninvasive in vivo imaging and biologic characterization of thyroid tumors by immunoPET targeting of galectin-3. Cancer Res. 2016;76:3583–92.PubMedCrossRef
27.
Chen Y, Huang Y, Reiberger T, Duyverman AM, Huang P, Samuel R, et al. Differential effects of sorafenib on liver versus tumor fibrosis mediated by stromal-derived factor 1 alpha/C-X-C receptor type 4 axis and myeloid differentiation antigen-positive myeloid cell infiltration in mice. Hepatology. 2014;59:1435–47.PubMedCrossRef
28.
Salem A, Asselin MC, Reymen B, Jackson A, Lambin P, West CML, et al. Targeting hypoxia to improve non-small cell lung cancer outcome. J Natl Cancer Inst. 2018;110:14–30.CrossRef
29.
De Bruycker S, Vangestel C, Van den Wyngaert T, Pauwels P, Wyffels L, Staelens S, et al. 18F-flortanidazole hypoxia PET holds promise as a prognostic and predictive imaging biomarker in a lung cancer xenograft model treated with metformin and radiotherapy. J Nucl Med. 2019;60:34–40.PubMedCrossRef
30.
Chen Y, Ramjiawan RR, Reiberger T, Ng MR, Hato T, Huang Y, et al. CXCR4 inhibition in tumor microenvironment facilitates anti-programmed death receptor-1 immunotherapy in sorafenib-treated hepatocellular carcinoma in mice. Hepatology. 2015;61:1591–602.PubMedCrossRef
31.
Conley SJ, Gheordunescu E, Kakarala P, Newman B, Korkaya H, Heath AN, et al. Antiangiogenic agents increase breast cancer stem cells via the generation of tumor hypoxia. Proc Natl Acad Sci U S A. 2012;109:2784–9.PubMedPubMedCentralCrossRef
32.
Peeters SG, Zegers CM, Biemans R, Lieuwes NG, van Stiphout RG, Yaromina A, et al. TH-302 in combination with radiotherapy enhances the therapeutic outcome and is associated with pretreatment [18F]HX4 hypoxia PET imaging. Clin Cancer Res. 2015;21:2984–92.PubMedCrossRef
33.
Jayaprakash P, Ai M, Liu A, Budhani P, Bartkowiak T, Sheng J, et al. Targeted hypoxia reduction restores T cell infiltration and sensitizes prostate cancer to immunotherapy. J Clin Invest. 2018;128:5137–49.PubMedPubMedCentralCrossRef
34.
Le QT, Shi G, Cao H, Nelson DW, Wang Y, Chen EY, et al. Galectin-1: a link between tumor hypoxia and tumor immune privilege. J Clin Oncol. 2005;23:8932–41.PubMedCrossRef
35.
Zhao XY, Chen TT, Xia L, Guo M, Xu Y, Yue F, et al. Hypoxia inducible factor-1 mediates expression of galectin-1: the potential role in migration/invasion of colorectal cancer cells. Carcinogenesis. 2010;31:1367–75.PubMedCrossRef
36.
Piert M, Machulla HJ, Picchio M, Reischl G, Ziegler S, Kumar P, et al. Hypoxia-specific tumor imaging with 18F-fluoroazomycin arabinoside. J Nucl Med. 2005;46:106–13.PubMed
37.
Pereira-Prado V, Vigil-Bastitta G, Sánchez-Romero C, Arocena M, Molina-Frechero N, González-González R, et al. Immunoexpression of galectin-3 and its potential relation to hypoxia-inducible factor-1α in ameloblastomas. Biotech Histochem. 2021;96:296–301.PubMedCrossRef
38.
van den Brule F, Califice S, Garnier F, Fernandez PL, Berchuck A, Castronovo V. Galectin-1 accumulation in the ovary carcinoma peritumoral stroma is induced by ovary carcinoma cells and affects both cancer cell proliferation and adhesion to laminin-1 and fibronectin. Lab Invest. 2003;83:377–86.PubMedCrossRef
39.
Satelli A, Rao PS, Gupta PK, Lockman PR, Srivenugopal KS, Rao US. Varied expression and localization of multiple galectins in different cancer cell lines. Oncol Rep. 2008;19:587–94.PubMed
40.
Koopmans SM, Bot FJ, Schouten HC, Janssen J, van Marion AM. The involvement of Galectins in the modulation of the JAK/STAT pathway in myeloproliferative neoplasia. Am J Blood Res. 2012;2:119–27.PubMedPubMedCentral
41.
Nagengast WB, Lub-de Hooge MN, Oosting SF, den Dunnen WF, Warnders FJ, Brouwers AH, et al. VEGF-PET imaging is a noninvasive biomarker showing differential changes in the tumor during sunitinib treatment. Cancer Res. 2011;71:143–53.PubMedCrossRef
42.
Gaykema SB, Brouwers AH, Lub-de Hooge MN, Pleijhuis RG, Timmer-Bosscha H, Pot L, et al. 89Zr-bevacizumab PET imaging in primary breast cancer. J Nucl Med. 2013;54:1014–8.PubMedCrossRef
43.
Viola-Villegas NT, Rice SL, Carlin S, Wu X, Evans MJ, Sevak KK, et al. Applying PET to broaden the diagnostic utility of the clinically validated CA19.9 serum biomarker for oncology. J Nucl Med. 2013;54:1876–82.
44.
Pereira PMR, Roberts S, Figueira F, Tomé JPC, Reiner T, Lewis JS. PET/CT imaging with an 18F-labeled galactodendritic unit in a galectin-1-overexpressing orthotopic bladder cancer model. J Nucl Med. 2020;61:1369–75.PubMedPubMedCentralCrossRef
45.
Bratteby K, Torkelsson E, L’Estrade ET, Peterson K, Shalgunov V, Xiong M, et al. In vivo veritas: 18F-radiolabeled glycomimetics allow insights into the pharmacological fate of galectin-3 inhibitors. J Med Chem. 2020;63:747–55.PubMedCrossRef
46.
Muzi M, Peterson LM, O’Sullivan JN, Fink JR, Rajendran JG, McLaughlin LJ, et al. 18F-fluoromisonidazole quantification of hypoxia in human cancer patients using image-derived blood surrogate tissue reference regions. J Nucl Med. 2015;56:1223–8.PubMedCrossRef
47.
Airley RE, Mobasheri A. Hypoxic regulation of glucose transport, anaerobic metabolism and angiogenesis in cancer: novel pathways and targets for anticancer therapeutics. Chemotherapy. 2007;53:233–56.PubMedCrossRef
48.
Leimgruber A, Hickson K, Lee ST, Gan HK, Cher LM, Sachinidis JI, et al. Spatial and quantitative mapping of glycolysis and hypoxia in glioblastoma as a predictor of radiotherapy response and sites of relapse. Eur J Nucl Med Mol Imaging. 2020;47:1476–85.PubMedCrossRef
49.
Busk M, Horsman MR, Kristjansen PE, van der Kogel AJ, Bussink J, Overgaard J. Aerobic glycolysis in cancers: implications for the usability of oxygen-responsive genes and fluorodeoxyglucose-PET as markers of tissue hypoxia. Int J Cancer. 2008;122:2726–34.PubMedCrossRef
50.
Yamamoto K, Brender JR, Seki T, Kishimoto S, Oshima N, Choudhuri R, et al. Molecular imaging of the tumor microenvironment reveals the relationship between tumor oxygenation, glucose uptake, and glycolysis in pancreatic ductal adenocarcinoma. Cancer Res. 2020;80:2087–93.PubMedPubMedCentralCrossRef
51.
52.
Metadaten
Titel
Galectin expression detected by 68Ga-galectracer PET as a predictive biomarker of radiotherapy resistance
verfasst von
Dehua Lu
Haoyi Zhou
Nan Li
Yanpu Wang
Ting Zhang
Fei Wang
Ning Liu
Hua Zhu
Jinming Zhang
Zhi Yang
Zhaofei Liu
Publikationsdatum
02.02.2022
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 8/2022
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-022-05711-1

Weitere Artikel der Ausgabe 8/2022

European Journal of Nuclear Medicine and Molecular Imaging 8/2022 Zur Ausgabe

Original Article

18F-Alfatide II for the evaluation of axillary lymph nodes in breast cancer patients: comparison with 18F-FDG

Original Article

Ultrafast 30-s total-body PET/CT scan: a preliminary study

Short Communication

Spatiotemporal dynamics of brain function during the natural course in a dental pulp injury model

Original Article

Expression of fibroblast activation protein in lung cancer and its correlation with tumor glucose metabolism and histopathology

Original Article

A self-triggered radioligand therapy agent for fluorescence imaging of the treatment response in prostate cancer

Original Article

A pure nanoICG-based homogeneous lipiodol formulation: toward precise surgical navigation of primary liver cancer after long-term transcatheter arterial embolization