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Targeted radiotherapy: microgray doses and the bystander effect.

Robert J Mairs¹, Natasha E Fullerton, Michael R Zalutsky

¹Targeted Therapy Group, Division of Cancer Science and Molecular Pathology, Glasgow University, Cancer Research UK Beatson Laboratories, Glasgow, UK. r.mairs@beatson.gla.ac.uk

Dose-Response : a Publication of International Hormesis Society

|July 24, 2008

Summary

Indirect effects in targeted radionuclide therapy differ from radiotherapy. High linear energy transfer (LET) radionuclides can cause bystander cell toxicity or protection, depending on the dose.

Keywords:

Radiopharmaceutical-induced bystander effect

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Area of Science:

Nuclear medicine
Radiation biology
Cellular effects of radiation

Background:

Indirect effects, or bystander effects, are known to enhance radiotherapy efficacy by impacting non-directly irradiated cells.
The influence of these indirect effects in targeted radionuclide therapy remains largely unexplored.

Purpose of the Study:

To compare gamma-radiation-induced bystander effects with those induced by three radiohaloanalogues of meta-iodobenzylguanidine (MIBG).
To investigate the role of linear energy transfer (LET) in radiopharmaceutical-induced bystander effects.

Main Methods:

Comparison of bystander effects induced by gamma radiation, [(131)I]MIBG (low LET), [(123)I]MIBG (high LET Auger emitter), and meta-[(211)At]astatobenzylguanidine ([(211)At]MABG) (high LET alpha-emitter).
Assessment of cell survival fraction after exposure to conditioned media from irradiated cells.

Main Results:

Gamma-irradiated cells induced dose-dependent bystander cell kill at low doses, plateauing at higher doses.
[(131)I]MIBG induced a dose-response relationship for cell death, without annihilation at high doses.
[(211)At]MABG and [(123)I]MIBG showed U-shaped survival curves, indicating toxicity at low doses and protection at high doses.

Conclusions:

Radiopharmaceutical-induced bystander effects are dependent on the linear energy transfer (LET) of the emitted radiation.
High LET radionuclides can elicit distinct toxic or protective effects on neighboring cells, differing from conventional radiotherapy bystander effects.