177Lu-SN201 nanoparticle shows superior anti-tumor efficacy over conventional cancer drugs in 4T1 orthotopic model

Invest New Drugs. 2024 Aug;42(4):471-477. doi: 10.1007/s10637-024-01450-2. Epub 2024 Jun 5.

Abstract

In the current in-vivo study we demonstrate the potential of the radiolabeled nanoparticle 177Lu-SN201 as an effective anticancer treatment, as evidenced by significantly prolonged survival and reduced tumor burden in the aggressive, triple negative 4T1 murine breast cancer model. We show with high statistical significance that 177Lu-SN201 is superior at suppressing the tumor growth not only compared to vehicle but also to the commonly used cancer drugs paclitaxel, niraparib, carboplatin, and the combination of the immune checkpoint inhibitors anti PD-1 and anti-CTLA-4. The dosing of the standard drugs were based on examples in the literature where good effects have been seen in various mouse models. The treatment is reasonably well-tolerated, as indicated by clinical chemistry of liver and renal function through the measurement of glutamate pyruvate alanine aminotransferase, alanine amino transferase, blood urea nitrogen, and creatinine levels in plasma samples, despite some weight loss. Overall, 177Lu-SN201 presents as a promising therapeutic candidate for cancer treatment.

Keywords: 177Lu; 177Lu-SN201; Cancer; Nanoparticle; Radiotherapy; Targeted radiotherapy.

MeSH terms

  • Animals
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Cell Line, Tumor
  • Female
  • Humans
  • Lutetium* / therapeutic use
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles*
  • Radioisotopes / pharmacology
  • Radioisotopes / therapeutic use

Substances

  • Lutetium
  • Antineoplastic Agents
  • Radioisotopes
  • Lutetium-177