Dosimetry-Guided Radiopharmaceutical Therapy-7DB0150D
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Radiopharmaceutical therapy (RPT) is a radiation delivery
modality that uses radionuclides to irradiate tissues with
various forms of ionizing radiation. In most forms of RPT,
the radionuclide is targeted to the diseased tissue following
systemic administration of the pharmaceutical that circulates
throughout the body and delivers radiation to sites of
radiopharmaceutical accumulation. Three major classes of
radionuclides are used in RPT including beta-particle emitters,
alpha-particle emitters, and Auger-electron emitters.
Recent therapeutic successes and regulatory approval of
some commercial radiopharmaceuticals have spurred development
of new agents. Unfortunately, comparisons of clinical
results and optimization of RPT are hindered by the
absence of standardized practices for prescribing, reporting,
and recording of dosimetric quantities related to RPT. The
present report provides information necessary to standardize
techniques and procedures and to harmonize the clinical
prescription, recording, and reporting of dosimetry for RPT
in a manner that facilitates the use of RPT alone or in combination
with other modalities. The Report’s introduction
briefly outlines the rationale and historical development of
RPT. Then fundamental concepts of radionuclides and radiation
dosimetry are reviewed. This is followed by a description
of the radiobiology of RPT as compared with external
photon radiation, along with bioeffect models used to calculate
relative biological effectiveness (RBE) and equieffective
dose for treatment planning. The cornerstone of the
report comprises key concepts and terminology needed to
implement dosimetry and treatment planning for RPT. These
definitions are used in the recommended absorbed dose prescriptions.
Essential to this end are reproducible procedures
for quantifying activity in the various source regions.
Accordingly, an extensive set of recommendations for activity
quantification are described within, along with how to
acquire and use pharmacokinetic data to obtain the time
integrated activity in source regions. This is followed by
methods to calculate the absorbed dose to the dosimetric
treatment regions and regions at risk (RARs). The implementation
of absorbed dose in RPT treatment planning, and
in combination therapies, is then addressed. Subsequent sections
describe recommendations for prescribing, recording,
and reporting treatments. The report ends with four clinical
examples of RPT for different tumor entities to illustrate the
application of the recommendations. Specific recommendations
in this report include the use of the quantity equieffective
dose (EQDX) in units of gray (Gy) which accounts for
the dependence of radiobiological responses on absorbed
dose rate, fractionation, and linear energy transfer (LET). To
avoid confusion, both absorbed dose and equieffective dose
should be specified. A new quantity, the standardized relative
biological effectiveness (sRBEX), is defined to facilitate
bioeffect modeling for high LET radiations such as
alpha particles and Auger electrons. In addition, new ICRU
definitions of regions and geometric concepts to be used in
RPT include localization regions, source regions, clinical
treatment regions, dosimetric treatment regions, and RARs;
reflecting a unique aspect of RPT relative to radiotherapy,
these regions may be delineable or nondelineable. Finally,
analogous to external beam radiation therapy, specific recommendations
for ICRU reporting levels for RPT are recommended
which are specific to each radiopharmaceutical.
The Report should be an important and useful reference for
all practitioners in RPT and should facilitate comparisons
of clinical results from different centers. The focus of
dosimetry-guided RPT makes explicit the potential of RPT
to target and control tumors while reducing normal tissue
toxicity. For all new users and interested readers, the
description of the basic concepts and background of RPT
should enable them to understand the techniques involved
in RPT.