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Related Experiment Videos

Oligoradionuclidetherapy using radiolabelled antisense oligodeoxynucleotide phosphorothioates

K J Kairemo1, M Tenhunen, A P Jekunen

  • 1Department of Oncology, Helsinki University Central Hospital, Finland.

Anti-Cancer Drug Design
|September 1, 1996
PubMed
Summary

Choosing the right radionuclide for oligonucleotide radiotherapy is key. Phosphorus-33 (33P) and Sulfur-35 (35S) offer better therapeutic characteristics than Phosphorus-32 (32P) for smaller tumors, while 32P is optimal for larger ones.

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Area of Science:

  • Nuclear Medicine
  • Radiotherapy
  • Oligonucleotide Therapeutics

Background:

  • Radiolabeled antisense oligodeoxynucleotides show potential for in vivo studies in AIDS and cancer.
  • Determining the optimal radionuclide source is crucial for therapeutic applications of radio-oligonucleotides.

Purpose of the Study:

  • To evaluate the pharmacokinetics and in vivo tissue distribution of oligodeoxynucleotide phosphorothioates labeled with three different radionuclides: sulfur-35 (35S), phosphorus-33 (33P), and phosphorus-32 (32P).
  • To compare the absorbed radiation doses and therapeutic potential of these radionuclides in animal models for tumor xenografts and AIDS.

Main Methods:

  • Utilized biodistribution data from three radionuclides (35S, 33P, 32P) in two animal models.
  • Estimated absorbed doses for 32P-, 33P-, and 35S-labeled oligonucleotides.

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  • Calculated radiation doses to tumors and normal organs (kidney, liver) based on oligonucleotide mass and injected activity.

    • Main Results:

    • Local energy absorption of 33P exceeded 32P for masses <300 micrograms; 35S exceeded 32P for masses <80 micrograms.
    • Sufficient tumor radiation doses were achievable with i.v. injected activity in a mouse xenograft model.
    • For a 1g tumor, doses were 4.9 Gy (32P), 5.1 Gy (33P), and 5.5 Gy (35S) with a kidney dose of 5 Gy.
    • For smaller tumors (1mg and 1µg), 33P and 35S delivered significantly higher doses than 32P.
    • No significant difference in radiation dose to normal organs (kidney, liver) was observed between the radionuclides.

    Conclusions:

    • Phosphorus-33 (33P) and sulfur-35 (35S) exhibit more beneficial radiotherapeutic characteristics than phosphorus-32 (32P).
    • For oligonucleotide radiotherapy, 32P is recommended for tumors >1g, while 33P or 35S are suitable for smaller tumors.
    • There is no significant difference between 33P and 35S, allowing selection based on labeling properties.