86/90Y-Based Theranostics Targeting Angiogenesis in a Murine Breast Cancer Model

Mol Pharm. 2018 Jul 2;15(7):2606-2613. doi: 10.1021/acs.molpharmaceut.8b00133. Epub 2018 May 30.

Abstract

Angiogenesis is widely recognized as one of the hallmarks of cancer. Therefore, imaging and therapeutic agents targeted to angiogenic vessels may be widely applicable in many types of cancer. To this end, the theranostic isotope pair, 86Y and 90Y, were used to create a pair of agents for targeted imaging and therapy of neovasculature in murine breast cancer models using a chimeric anti-CD105 antibody, TRC105. Serial positron emission tomography imaging with 86Y-DTPA-TRC105 demonstrated high uptake in 4T1 tumors, peaking at 9.6 ± 0.3%ID/g, verified through ex vivo studies. Additionally, promising results were obtained in therapeutic studies with 90Y-DTPA-TRC105, wherein significantly ( p < 0.05) decreased tumor volumes were observed for the targeted treatment group over all control groups near the end of the study. Dosimetric extrapolation and tissue histological analysis corroborated trends found in vivo. Overall, this study demonstrated the potential of the pair 86/90Y for theranostics, enabling personalized treatments for cancer.

Keywords: CD105/endoglin; angiogenesis; cancer; positron emission tomography (PET); radioimmunotherapy; theranostics; yttrium-86; yttrium-90.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor / transplantation
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Immunoconjugates / chemistry
  • Immunoconjugates / pharmacology*
  • Immunoconjugates / therapeutic use
  • Mammary Neoplasms, Experimental / diagnostic imaging
  • Mammary Neoplasms, Experimental / pathology
  • Mammary Neoplasms, Experimental / radiotherapy*
  • Mice
  • Mice, Inbred BALB C
  • Neovascularization, Pathologic / diagnostic imaging
  • Neovascularization, Pathologic / drug therapy*
  • Positron-Emission Tomography / methods
  • Radioimmunotherapy / methods*
  • Theranostic Nanomedicine / methods*
  • Tissue Distribution
  • Treatment Outcome
  • Yttrium Radioisotopes / chemistry
  • Yttrium Radioisotopes / pharmacology
  • Yttrium Radioisotopes / therapeutic use

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Immunoconjugates
  • Yttrium Radioisotopes
  • Yttrium-86
  • Yttrium-90
  • carotuximab