Risks to Normal Tissues From Radionuclide Therapy
Section snippets
Theoretical Radiobiologic Models for Radionuclide Therapy
The linear quadratic (LQ) model that is now used extensively in clinical radiobiology was outlined by Fowler and Stern in 1960.12, 13 The model is based on a single-hit cell kill (Type A event), which corresponds to a lethal single-ionization event and is thus independent of dose rate. A second (Type B) event can only be induced by 2 separate ionization interactions and is thus a function of dose rate. The LQ equation for the surviving fraction (SF) of cells after an instantaneously delivered
Toxicity Monitoring
There are accepted standard toxicity scoring criteria that have been applied to various therapeutic agents, including cytotoxic chemotherapy agents, biologics, gene therapy, external beam radiation, and radionuclides. The most common types of toxicity may vary with modality, such as fibrosis associated with radiation and peripheral neuropathy that may result from chemotherapy. Because chemotherapy or other agents (such as biologics or radiation sensitizers/protectors) are frequently used with
Whole and Partial Organ Tolerance
In most instances, tolerance information is useful to avoid irreversible organ compromise, whereas in some instances dysfunction is the desired effect, such as 131I for thyroid ablation. The concept of minimal and maximal tissue tolerance dose was introduced by Rubin and Caserett and applied to whole or partial organ volume that received a uniform dose of external beam radiation at conventional high dose rate (>100 cGy/min) daily fractionations of 1.8 to 2Gy.48 Data were compiled from
Conclusion
Some principles can be concluded from data reviewed here and other studies of radionuclide effects on normal tissues:
- 1
Dose rate affects tolerance.
- 2
Fractionation increases tolerance of cumulative radionuclide dose.
- 3
Small doses may have more carcinogenic effects compared with higher doses that may compromise organ function.
- 4
Heterogeneous distribution affects whole organ tolerance.
- 5
Subunits of organs such as kidney and central nervous system have different tolerance.
- 6
Tolerance varies among individuals
Acknowledgments
We are grateful to Roger Dale for a major contribution to the Theoretical Radiobiologic Models section, Hazel Breitz for discussion and Tracey Cotton-Young for manuscript preparation assistance.
References (136)
Dose fractionation, dose rate and iso-effect relationships for normal tissue responses
Int J Radiat Oncol Biol Phys
(1982)Radiobiological aspects of low dose rates in radioimmunotherapy
Int J Radiat Oncol Biol Phys
(1990)- et al.
Cerebral radiation necrosis: incidence, outcomes, and risk factors with emphasis on radiation parameters and chemotherapy
Int J Radiat Oncol Biol Phys
(2006) - et al.
Low-dose radiation effects: experimental hematology and the changing paradigm
Exp Hematol
(2003) - et al.
PARP-1, a determinant of cell survival in response to DNA damage
Exp Hematol
(2003) - et al.
Modulation of intercellular communication mediated at the cell surface and on extracellular, plasma membrane-derived vesicles by ionizing radiation
Exp Hematol
(2003) - et al.
Improving the capture of adverse event data in clinical trials: The role of the International Atomic Energy Agency
Int J Radiat Oncol Biol Phys
(2007) - et al.
CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment
Semin Radiat Oncol
(2003) - et al.
Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC)
Int J Radiat Oncol Biol Phys
(1995) - et al.
The calculated risk of fatal secondary malignancies from intensity-modulated radiation therapy
Int J Radiat Oncol Biol Phys
(2005)
Radiation exposure and familial aggregation of cancers as risk factors for colorectal cancer after radioiodine treatment for thyroid carcinoma
Int J Radiat Oncol Biol Phys
High-dose radioiodine treatment for differentiated thyroid carcinoma is not associated with change in female fertility or any genetic risk to the offspring
Int J Radiat Oncol Biol Phys
Assessment of treatment-related myelodysplastic syndromes and acute myeloid leukemia in patients with non-Hodgkin lymphoma treated with tositumomab and iodine I131 tositumomab
Blood
Tolerance of normal tissue to therapeutic irradiation
Int J Radiat Oncol Biol Phys
Optimization of radiation therapy, IV: A dose-volume histogram reduction algorithm
Int J Radiat Oncol Biol Phys
Normal tissue tolerance dose metrics for radiation therapy of major organs
Semin Radiat Oncol
Use of principal component analysis to evaluate the partial organ tolerance of normal tissues to radiation
Int J Radiat Oncol Biol Phys
Personal thoughts on normal tissue tolerance, or, what the textbooks don't tell you
Int J Radiat Oncol Biol Phys
Inclusion of biological factors in parallel-architecture normal-tissue complication probability model for radiation-induced liver disease
Int J Radiat Oncol Biol Phys
Application of the linear-quadratic model to combined modality radiotherapy
Int J Radiat Oncol Biol Phys
Pathologic response and microdosimetry of (90)Y microspheres in man: Review of four explanted whole livers
Int J Radiat Oncol Biol Phys
Selective tumor irradiation by infusional brachytherapy in nonresectable pancreatic cancer: A phase I study
Int J Radiat Oncol Biol Phys
A phase I trial of stereotactic body radiation therapy (SBRT) for liver metastases
Int J Radiat Oncol Biol Phys
Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: Final report of RTOG protocol 90-05
Int J Radiat Oncol Biol Phys
12 Gy gamma knife radiosurgical volume is a predictor for radiation necrosis in non-AVM intracranial tumors
Int J Radiat Oncol Biol Phys
Whole brain radiotherapy with hippocampal avoidance and simultaneously integrated brain metastases boost: A planning study
Int J Radiat Oncol Biol Phys
Dose and diameter relationships for facial, trigeminal and acoustic neuropathies following acoustic neuroma radiosurgery
Radiother Oncol
Dosimetry and dose-response relationships in newly diagnosed patients with malignant gliomas treated with iodine-131-labeled anti-tenascin monoclonal antibody 81C6 therapy
Int J Radiat Oncol Biol Phys
Update of human spinal cord reirradiation tolerance based on additional data from 38 patients
Int J Radiat Oncol Biol Phys
Clinical trial design and scoring of radionuclide therapy endpoints: Normal organ toxicity and tumor response
Cancer Biother Radiopharm
Determinants of the antitumor effect of radiolabeled monoclonal antibodies
Cancer Res
Low-dose-rate irradiation by 131I versus high-dose-rate external-beam irradiation in the rat pancreatic tumor cell line CA20948
Cancer Biother Radiopharm
Log normal distribution of cellular uptake of radioactivity: Implications for biologic responses to radiopharmaceuticals
J Nucl Med
Requirements regarding dose rate and exposure time for killing of tumour cells in beta particle radionuclide therapy
Eur J Nucl Med Mol Imaging
Receptor radionuclide therapy with 90Y-[DOTA]0-Tyr3-octreotide (90Y-DOTATOC) in neuroendocrine tumours
Eur J Nucl Med Mol Imaging
Radioimmunotherapy of Cancer
Radioimmunotherapy for NHL: Experience of 90Y-ibritumomab tiuxetan in clinical practice
Leuk Lymphoma
Plasma FLT3-L levels predict bone marrow recovery from myelosuppressive therapy
Cancer
Targeted alpha radiation and gamma rays induce significantly different molecular responses in human leukemic lymphocytes as revealed by gene expression profiling
J Nucl Med
MIRD continuing education: Bystander and low dose-rate effects: are these relevant to radionuclide therapy?
J Nucl Med
Dose-rate effects: Some theoretical and practical considerations
Br J Radiol
An ‘incomplete-repair’ model for survival after fractionated and continuous irradiations
Int J Radiat Biol Relat Stud Phys Chem Med
Radiobiology of radiolabeled antibody therapy as applied to tumor dosimetry
Med Phys
Dose-rate effects in targeted radiotherapy
Phys Med Biol
Optimal therapeutic strategies for radioimmunotherapy
Recent Results Cancer Res
Proliferation and the advantage of longer-lived radionuclides in radioimmunotherapy
Med Phys
Absorbed dose averages and dose heterogeneities in Radioimmunotherapy
Antibody Immunoconjugates and Radiopharmaceuticals
Fractionation in Radiotherapy
Radiobiologic principles in radionuclide therapy
J Nucl Med
Dosimetry of internal emitters
J Nucl Med
Cited by (23)
Targets for Therapy of Bladder Cancer
2020, Seminars in Nuclear MedicineCitation Excerpt :As calculations for the absorbed dose to the bladder wall have revealed, the maximum Bi-213-anti-EGFR-MAb activity applied intravesivally (821 MBq) caused an absorbed dose of 3.86 Gy.42 As stated by Meredith et al43, the bladder wall could tolerate up to 40 Gy without showing adverse effects. Therefore, an enhancement of the applied activity of Bi-213-anti-EGFR-MAb seems promising.
Preclinical Evaluation of the Acute Radiotoxicity of the α-Emitting Molecular-Targeted Therapeutic Agent <sup>211</sup>At-MABG for the Treatment of Malignant Pheochromocytoma in Normal Mice
2019, Translational OncologyCitation Excerpt :The changes revealed that the dose of 3.3 MBq was the MTD for ICR mice under our experimental conditions. After administration of 3.3 MBq of 211At-MABG, the estimated absorbed doses in the heart, lungs, liver, spleen, stomach, kidneys, and thyroid were markedly greater than the MTD of radiation: 40 Gy for the heart, 17.5 Gy for the lungs, 30 Gy for the liver, 20 Gy for the spleen, 50 Gy for the stomach, 23 Gy for the kidneys, and 45 Gy for the thyroid [30–33]. The adrenal glands are radioresistant, and irreversible radiation-induced damage has not been reported to date; consequently, the MTD has not been established [34,35].
Targeted Radionuclide Therapy
2015, Clinical Radiation OncologyTargeted Radionuclide Therapy
2012, Clinical Radiation Oncology: Third EditionDosimetry in molecular nuclear therapy
2011, MethodsCitation Excerpt :Estimation of an acceptable dose is complicated because radiation tolerance in radionuclide therapy varies among individuals, with influence of genetic makeup, age and previous therapies. Meredith et al. reviewed the risks to normal tissue from radionuclide therapy [93]. They noted that the tolerance of normal tissue often appeared to be greater than in external beam radiotherapy, but at the same time more variable.
Support for some clinical trials was from NIH M01 RR-00032.