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Alpha-particle radiotherapy: For large solid tumors diffusion trumps targeting.

Charles Zhu1, Michelle Sempkowski1, Timothy Holleran1

  • 1Departments of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, NJ 08854, USA.

Biomaterials
|April 3, 2017
PubMed
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Assessing the imaging calibration factor for quantitative SPECT/CT of actinium-225.

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This summary is machine-generated.

Targeted delivery of alpha-particle emitters to solid tumors is challenging. This study developed pH-tunable liposomes that release Actinium-225 in tumors, improving irradiation and survival in mouse models.

Area of Science:

  • Nanomedicine
  • Radiopharmaceutical Therapy
  • Oncology

Background:

  • Diffusion limitations of nanocarriers in solid tumors hinder alpha-particle emitter therapy.
  • Short alpha-particle range (≤100 μm) leads to incomplete tumor irradiation and reduced efficacy.
  • Need for strategies to overcome diffusion barriers for effective solid tumor treatment.

Purpose of the Study:

  • To design non-internalizing nanocarriers for triggered release of alpha-particle generators within solid tumors.
  • To improve homogeneous distribution and penetration of alpha-particle emitters for enhanced tumor killing.
  • To evaluate the efficacy of pH-tunable liposomes releasing Actinium-225 in preclinical models.

Main Methods:

  • Development of pH-tunable liposomes encapsulating Actinium-225 (225Ac).
Keywords:
Actinium-225Interstitial transportSolid tumorsTumor penetrationpH-responsive liposomesα-particle therapy

Related Experiment Videos

  • Testing on multicellular spheroids (400 μm) as tumor surrogates.
  • In vivo evaluation in an orthotopic human HER2-negative mouse model.

    • Main Results:

    • Interstitially-releasing liposomes demonstrated superior growth control on spheroids, outperforming HER2-targeting antibodies and non-responsive liposomes.
    • pH-tunable liposomes achieved homogeneous distribution of 225Ac within tumor spheroids.
    • In vivo studies showed significantly improved overall and median survival in mice treated with 225Ac-loaded liposomes.

    Conclusions:

    • pH-tunable liposomes offer a promising strategy to bypass nanocarrier diffusion limitations in solid tumors.
    • This approach enables interstitial release of highly-diffusive alpha-particle emitters, enhancing tumor irradiation and therapeutic outcomes.
    • The non-targeting, non-internalizing nanocarrier strategy is effective independent of tumor cell targeting or HER2 expression.