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Folate receptor targeted alpha-therapy using terbium-149.

Cristina Müller1, Josefine Reber2, Stephanie Haller3

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Pharmaceuticals (Basel, Switzerland)
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Terbium-149 (149Tb) conjugated to DOTA-folate demonstrated significant anticancer effects in preclinical models. This targeted alpha radionuclide therapy showed reduced cancer cell viability and prolonged survival in tumor-bearing mice with no observed acute toxicity.

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Area of Science:

  • Nuclear Medicine
  • Oncology
  • Radiopharmaceutical Therapy

Background:

  • Terbium-149 (149Tb) is a promising therapeutic nuclide for alpha-particle emission therapy.
  • Folate receptor (FR) targeted therapies are being explored for enhanced cancer treatment.

Purpose of the Study:

  • To evaluate the in vitro and in vivo anticancer efficacy of a 149Tb-labeled DOTA-folate conjugate (cm09).
  • To assess the therapeutic potential of targeted alpha radionuclide therapy using 149Tb-cm09 in FR-positive cancers.

Main Methods:

  • Production of 149Tb at the ISOLDE facility at CERN.
  • Radiolabeling of DOTA-folate (cm09) with 149Tb.
  • In vitro cytotoxicity assays on FR-positive cancer cells.
  • In vivo studies in tumor-bearing mice treated with varying activities of 149Tb-cm09.

Main Results:

  • 149Tb-cm09 exhibited FR-specific and dose-dependent reduction in cancer cell viability in vitro.
  • Significant tumor growth delay and increased survival time were observed in mice treated with 149Tb-cm09.
  • No acute toxicity to kidneys or liver was detected in treated mice.

Conclusions:

  • Folate-based alpha-radionuclide therapy with 149Tb-cm09 shows significant therapeutic potential against FR-positive tumors.
  • Targeted delivery of 149Tb offers a promising strategy for cancer treatment with a favorable safety profile in preclinical models.