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Radiobiology and Radiation Dosimetry in Nuclear Medicine

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Nuclear Oncology

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Abstract

Radionuclide therapy (RNT) uses systemically administered radiopharmaceuticals directed to a specific cancer-associated target to provide low-dose rate (LDR) treatment. The radiation dose is delivered to the tumor cells by continuous, but declining, exposure that is a function of the initial uptake and the variable half-life. The average dose rate for RNT is typically of the order of 2–8 Gy/day, and the maximum absorbed dose may be up to 50 Gy delivered over a period of many days. This is in marked contrast to the situation with external beam radiotherapy (EBRT), where the dose is delivered at a high-dose rate (HDR), typically 1–5 Gy/min, and also to the dose rate at which brachytherapy is delivered, typically 1–5 Gy/h. The mechanisms by which cells respond to LDR exposures are different from those occurring at HDR. LDR exposures tend to promote loss of clonogenic potential in some cell types (e.g., lymphomas) by activating apoptotic responses, whereas high doses tend to cause necrosis as their primary mechanism of cytotoxicity. The ability to induce apoptosis varies inversely with dose rate. Many cell types exhibit an initial hypersensitive response at doses below ∼25 cGy, followed by a region of increasing radioresistance up to ∼50 cGy. This phenomenon probably involves an alteration in the cellular processing/repair of DNA damage as a function of dose. Radiation damage to cells is due primarily to indirect effects such as formation of free radicals in water (with their diffusion and subsequent interaction with cellular components, mostly DNA) and to some degree direct damage to DNA. Different tissues and different individuals have different abilities to respond to and repair this damage. The value of LDR therapy with radionuclides in patients with differentiated thyroid carcinoma, somatostatin receptor-expressing tumors, neuroendocrine tumors, lymphoma, liver tumors, neuroendocrine malignancies, prostate cancer, and treatment of metastatic bone pain is discussed.

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Abbreviations

ASCT:

Autologous stem cell transplantation

BED:

Biologic effective dose

BSA:

Body surface area

CRPC:

Castration-resistant prostate cancer

CT:

X-ray computed tomography

CTDI:

CT dose index

3D-ID:

3D-internal

DMSA:

Dimercaptosuccinic acid

DOTA:

1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid

DOTANOC:

DOTA-1-Nal3-octreotide

DOTATATE:

DOTA-Tyr3-octreotate

DSB:

Double-strand breaks

DTC:

Differentiated thyroid cancer

DTPA:

Diethylenetriaminepentaacetic acid

DVH:

Dose–volume histograms

EANM:

European Association of Nuclear Medicine

EBRT:

External beam radiation therapy

ECD:

Ethyl cysteinate dimer

ED:

Effective dose

EU:

European Union

[18F]FDG:

2-deoxy-2-[18F]fluoro-d-glucose

FDA:

The United States Food and Drug Administration

FISH:

Fluorescence in situ hybridization

FSH:

Follicle-stimulating hormone

GBE:

Ginkgo biloba extract

GI:

Gastrointestinal

Gy:

Gray unit (ionizing radiation dose in the International System of Units, corresponding to the absorption of one joule of radiation energy per kilogram of matter)

γ-H2AX:

Phosphorylated member X of the H2A histone family

HCC:

Hepatocellular carcinoma

HDR:

High-dose rate

HMPAO:

Hexamethylpropylenamine oxine

ICRU:

International Commission on Radiological Units

LDH–IRR:

Low-dose hyper-radiosensitivity–increased radioresistance

LDR:

Low-dose rate

LET:

Linear energy transfer

LPL:

Lethal–potentially lethal

LQ:

Linearquadratic

LSF:

Lung shunt fraction

LSS:

Life span study

MAA:

Macroaggregated albumin

MAG3:

Mercaptoacetyltriglycine

MDP:

Methylene diphosphonate

MIBG:

Meta-iodobenzylguanidine

MIRD:

Medical internal radiation dose

mCRPC:

Metastatic castration-resistant prostate cancer

MRI:

Magnetic resonance imaging

MN:

Micronuclei

NAT:

Noradrenaline transporter

NHL:

Non-Hodgkin’s lymphoma

NSCLC:

Non-small cell lung cancer

NT:

Non-tumor tissue

NTCP:

Normal tissue complication probability

OLINDA:

Organ-level internal dose assessment

PET:

Positron emission tomography

PET/CT:

Positron emission tomography/Computed tomography

PET/MRI:

Positron emission tomography/Magnetic resonance imaging

PRLT:

PSMA-radioligand therapy

PRRT:

Peptide receptor radionuclide therapy

PSMA:

Prostate-specific membrane antigen

RBE:

Relative biological effectiveness

RE:

Relative effectiveness per unit dose

RILD:

Radiation-induced liver disease

RIT:

Radioimmunotherapy

RNT:

Radionuclide therapy

ROI:

Region of interest

ROS:

Reactive oxygen species

SF:

Surviving fraction

SNM:

Society of Nuclear Medicine

SPECT:

Single-photon emission computed tomography

SPECT/CT:

Single-photon emission computed tomography/Computed tomography

STASIS:

Stress or aberrant signaling-induced senescence

SUV:

Standardized uptake values

Sv:

Unit of radiation absorption in the International System of Units (SI), which takes into account the relative biological effectiveness (RBE) of ionizing radiation

TACE:

Transarterial chemoembolization

TARE:

Trans-arterial radioembolization

TBA:

Total-body absorbed

TCP:

Tumor control probability

TNF:

Tumor necrosis factor

TRAIL:

TNF-related apoptosis-inducing ligand

VOI:

Volume of interest

WBD:

Whole-body radiation dose

WBS:

Whole-body scan

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Authors and Affiliations

  1. Nuclear Medicine Institute, Catholic University of the Sacred Heart – “Policlinico A. Gemelli”, Rome, Italy

    Massimo Salvatori

  2. Department of Medical Physics, European Institute of Oncology, Milan, Italy

    Marta Cremonesi

  3. Department of Medical Physics, Catholic University of the Sacred Heart – “Policlinico A. Gemelli”, Rome, Italy

    Luca Indovina

  4. Department of Endocrinology, “Ospedale Regina Apostolorum”, Rome, Italy

    Marco Chianelli

  5. Department of Medical Physics, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy

    Massimiliano Pacilio

  6. Università degli Studi di Pavia, Pavia, Italy

    Rachele Danieli

  7. Nuclear Medicine Department, National Cancer Institute, Milan, Italy

    Carlo Chiesa

  8. Department of Medical Physics, Memorial Hospital Research Laboratories, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Pat Zanzonico

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  1. Massimo Salvatori
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  2. Marta Cremonesi
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  3. Luca Indovina
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  4. Marco Chianelli
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  5. Massimiliano Pacilio
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  6. Rachele Danieli
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  7. Carlo Chiesa
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  8. Pat Zanzonico
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Corresponding author

Correspondence to Massimo Salvatori .

Editor information

Editors and Affiliations

  1. Nuclear Medicine Unit Department of Translational Research and Advanced Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy

    Duccio Volterrani

  2. Nuclear Medicine Unit Department of Translational Research and Advanced Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy

    Paola A. Erba

  3. Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    H. William Strauss

  4. Nuclear Medicine Unit Department of Translational Research and Advanced Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy

    Giuliano Mariani

  5. Molecular Imaging and Targeted Therapy Service Department of Radiology, Sloan Kettering Institute, New York, NY, USA

    Steven M. Larson

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Salvatori, M. et al. (2022). Radiobiology and Radiation Dosimetry in Nuclear Medicine. In: Volterrani, D., Erba, P.A., Strauss, H.W., Mariani, G., Larson, S.M. (eds) Nuclear Oncology. Springer, Cham. https://doi.org/10.1007/978-3-031-05494-5_6

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  • DOI: https://doi.org/10.1007/978-3-031-05494-5_6

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