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Cited by 15Photodynamic Therapy Research StudiesNanoplatforms for cancer theranosticsPancreatic function and diabetes

Receptor-Targeted Photodynamic Therapy of Glucagon-Like Peptide 1 Receptor–Positive Lesions

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Boss, Marti, Bos, Desiree, Frielink, Cathelijne, Sandker, Gerwin, Bronkhorst, Patricia, van Lith, Sanne A.M., Brom, Maarten, Buitinga, Mijke +1 more·2020·Journal of Nuclear Medicine
DOI 10.2967/jnumed.119.238998PMC PMC8679620
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Abstract

Treatment of hyperinsulinemic hypoglycemia is challenging. Surgical treatment of insulinomas and focal lesions in congenital hyperinsulinism is invasive and carries major risks of morbidity. Medication to treat nesidioblastosis and diffuse congenital hyperinsulinism has varying efficacy and causes significant side effects. Here, we describe a novel method for therapy of hyperinsulinemic hyperglycemia, highly selectively killing β-cells by receptor-targeted photodynamic therapy (rtPDT) with exendin-4-IRDye700DX, targeting the glucagon-like peptide 1 receptor (GLP-1R). Methods: A competitive binding assay was performed using Chinese hamster lung (CHL) cells transfected with the GLP-1R. The efficacy and specificity of rtPDT with exendin-4-IRDye700DX were examined in vitro in cells with different levels of GLP-1R expression. Tracer biodistribution was determined in BALB/c nude mice bearing subcutaneous CHL-GLP-1R xenografts. Induction of cellular damage and the effect on tumor growth were analyzed to determine treatment efficacy. Results: Exendin-4-IRDye700DX has a high affinity for the GLP-1R, with a half-maximal inhibitory concentration of 6.3 nM. rtPDT caused significant specific phototoxicity in GLP-1R–positive cells (2.3% ± 0.8% and 2.7% ± 0.3% remaining cell viability in CHL-GLP-1R and INS-1 cells, respectively). The tracer accumulates dose-dependently in GLP-1R–positive tumors. In vivo, rtPDT induces cellular damage in tumors, shown by strong expression of cleaved caspase-3, and leads to a prolonged median survival of the mice (36.5 vs. 22.5 d, respectively; P < 0.05). Conclusion: These data show in vitro as well as in vivo evidence of the potency of rtPDT using exendin-4-IRDye700DX. This approach might in the future provide a new, minimally invasive, highly specific treatment method for hyperinsulinemic hypoglycemia.

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  • Boss et al. demonstrated selective destruction of lesions that express GLP-1R by coupling exendin-4 with a photosensitizer.

    “By coupling exendin-4 with a photosensitizer, Boss et al. demonstrated the selective destruction of lesions that express GLP-1R [101].”

    From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [101]

    The Results (page unavailable) show selective killing of GLP-1R–positive cells with exendin-4 coupled to a photosensitizer, and apoptosis and slower growth in GLP-1R–positive tumors. The Discussion says this effect might enable destruction of lesions; it does not report that lesions were selectively destroyed. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Boss and colleagues presented cell culture and mouse in vivo data on selective destruction of GLP-1-expressing cells via targeted photodynamic therapy.

    “Boss and colleagues presented cell culture and mouse in vivo data on selective destruction of GLP-1-expressing cells via targeted photodynamic therapy.”

    From An Uncommon Cause of Recurrent Presyncope, Dizziness, and Tachycardia: A Case Report of Diffuse, Adult-Onset Nesidioblastosis/Non-Insulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS) (2023) · cites this paper as [70]

    The Results sections report selective cell death in GLP-1R–positive cell cultures and cellular damage in GLP-1R–positive tumors in mice. The claim calls the targets “GLP-1-expressing cells,” but the paper identifies them as cells expressing the GLP-1 receptor (GLP-1R), not GLP-1 itself. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 32

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Cited by

Sorted by citations

Authors
Boss, M., Bos, D., Frielink, C., Sandker, G., Bronkhorst, P., van Lith, S. A. M., Brom, M., Buitinga, M., & Gotthardt, M.
Affiliations
Radboud University Medical Center (NL)
Corresponding author
Boss, Marti
ORCID
Venue
Journal of Nuclear Medicine
Publisher
Society of Nuclear Medicine
Published
2020-05-08
Volume
61
Issue
11
Pages
1588-1593
ISSN
  • 0161-5505 (ISSN-L)
  • 2159-662X
DOI
10.2967/jnumed.119.238998
PMC
PMC8679620
OpenAlex
W3021606396
Cited by
15
References
0
Citations by year
2025: 2 · 2024: 1 · 2023: 5 · 2022: 5 · 2021: 1 · 2020: 1
FWCI
1.69
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Journal of Nuclear Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Radboud Repository (Radboud University) (submittedVersion, other-oa)
  • Radboud Repository (Radboud University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
  • Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
GLP-1 receptor, hyperinsulinemic hypoglycemia, insulinoma, congenital hyperinsulinism, nesidioblastosis, tumor xenografts, caspase-3, minimally invasive therapy
MeSH terms
Glucagon-Like Peptide-1 Receptor, Exenatide, Animals, Cricetulus, Female, Cricetinae, Humans, Indoles, Mice, Inbred BALB C, Photochemotherapy, Organosilicon Compounds, Congenital Hyperinsulinism, Cell Line, Tumor, Nesidioblastosis, Mice, Rats

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