Noninvasive intravital high-resolution imaging of pancreatic neuroendocrine tumours

Mirela Balan1, Marta Trusohamn1, Frank Chenfei Ning1

  • 1Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, 17165, Sweden.

Scientific Reports
|October 12, 2019
PubMed

Insights

Researchers developed a novel eye-based imaging platform for real-time study of pancreatic neuroendocrine tumors (PNETs). This method allows high-resolution monitoring of PNET progression and drug response in a preclinical cancer model.

Area of Science:

  • Oncology
  • Preclinical Research
  • Biomedical Imaging

Background:

  • Pancreatic neuroendocrine tumors (PNETs) are challenging to study in real-time due to their location.
  • The Rip1Tag2 (RT2) mouse model is crucial for PNET research but lacks in-situ monitoring capabilities.
  • Developing accessible models is vital for advancing PNET drug development.

Purpose of the Study:

  • To establish a novel platform for intravital 3D imaging of RT2 mouse PNETs.
  • To enable real-time monitoring of PNET progression and angiogenesis.
  • To facilitate high-resolution assessment of preclinical cancer drug efficacy.

Main Methods:

  • Implantation of pre-oncogenic RT2 islets into the anterior chamber of the eye (ACE) of host mice.
  • Noninvasive confocal and two-photon laser-scanning microscopy through the transparent cornea for high-resolution imaging.
  • Utilizing genetically encoded fluorescent reporters for cellular and molecular visualization.

Main Results:

  • RT2 tumors successfully engrafted and grew in the ACE, exhibiting hallmarks of pancreatic tumors.
  • Tumor volume increased up to 8-fold, with significant angiogenesis observed.
  • Sunitinib treatment inhibited tumor angiogenesis and growth; VEGF-B overexpression increased angiogenesis but impaired tumor growth.
  • The platform allowed detailed imaging of tumor cell migration and stromal interactions.

Conclusions:

  • A novel and effective platform for intravital 3D imaging of PNETs in a preclinical model has been developed.
  • This platform provides unprecedented opportunities for real-time studies of PNET biology and drug assessment.
  • The ACE model offers a powerful tool for advancing pancreatic cancer research and therapeutic strategies.

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