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Updated: Jan 22, 2026

Targeted DNA Methylation Analysis by Next-generation Sequencing
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Norepinephrine-Transporter-Targeted and DNA-Co-Targeted Theranostic Guanidines

Zbigniew P Kortylewicz1, Donald W Coulter2, Guang Han1,3

  • 1Department of Radiation Oncology, J. Bruce Henriksen Cancer Research Laboratories, University of Nebraska Medical Center, Omaha, Nebraska 68132-6850, United States.

Journal of Medicinal Chemistry
|July 4, 2019
PubMed

Insights

New theranostic guanidines target neuroblastoma cells, incorporating into DNA and causing tumor regression. This DNA-targeting approach offers a promising new treatment for high-risk neuroblastoma, showing significant tumor retention and regression in preclinical models.

Area of Science:

  • Oncology
  • Radiochemistry
  • Molecular Biology

Background:

  • High-risk neuroblastoma frequently recurs despite intensive therapies.
  • Cellular proliferation is a key indicator of poor prognosis in neuroblastoma.
  • Novel therapeutic strategies are needed to overcome treatment resistance.

Purpose of the Study:

  • To synthesize and characterize novel theranostic guanidines for neuroblastoma.
  • To evaluate the DNA-targeting and therapeutic potential of these agents.
  • To assess the efficacy of guanidine-based radiopharmaceuticals in preclinical neuroblastoma models.

Main Methods:

  • Synthesis and characterization of novel guanidine compounds.
  • Assessment of cellular uptake and DNA incorporation in neuroblastoma cells.
  • In vivo biodistribution and efficacy studies in a mouse neuroblastoma xenograft model.
  • Evaluation of radiotoxicity correlated with DNA uptake and exposure duration.

Main Results:

  • Theranostic guanidines were successfully synthesized and characterized.
  • Active transport of guanidines into neuroblastoma cells was confirmed, with competitive inhibition observed.
  • Radioiodinated guanidines demonstrated efficient intracellular processing and DNA incorporation.
  • Significant tumor retention of radioactivity and regression of neuroblastoma xenografts were observed.
  • Radiotoxicity was directly proportional to DNA uptake and exposure time.

Conclusions:

  • Novel theranostic guanidines effectively target neuroblastoma cells via norepinephrine transporter.
  • These agents are incorporated into the DNA of proliferating neuroblastoma cells, leading to radiotoxicity.
  • Preclinical studies demonstrate significant tumor regression, supporting their potential as a new therapeutic option for high-risk neuroblastoma.

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