Biokinetics and dosimetry of commonly used radiopharmaceuticals in diagnostic nuclear medicine – a review
Jrn Hendrik Brer
Purpose The impact on patients' health of radiopharmaceuticals in nuclear medicine diagnostics has not until now been evaluated systematically in a European context. Therefore, as part of the EU-funded Project PEDDOSE. NET (www.peddose.net), we review and summarize the current knowledge on biokinetics and dosimetry of commonly used diagnostic radiopharmaceuticals. Methods A detailed literature search on published biokinetic and dosimetric data was performed mostly via PubMed (www.ncbi.nlm.nih.gov/pubmed). In principle the criteria for inclusion of data followed the EANM Dosimetry Committee guidance document on good clinical reporting. Results Data on dosimetry and biokinetics can be difficult to find, are scattered in various journals and, especially in paediatric nuclear medicine, are very scarce. The data collection and calculation methods vary with respect to the time-points, bladder voiding, dose assessment after the last data point and the way the effective dose was calculated. In many studies the number of subjects included for obtaining biokinetic and dosimetry data was fewer than ten, and some of the biokinetic data were acquired more than 20 years ago. Conclusion It would be of interest to generate new data on biokinetics and dosimetry in diagnostic nuclear medicine using state-of-the-art equipment and more uniform dosimetry protocols. For easier public access to dosimetry data for diagnostic radiopharmaceuticals, a database containing these data should be created and maintained.
Diagnostic procedures imply the administration of activity
levels that do not lead to the appearance of radiation
deterministic effects; therefore only stochastic risks have to
be considered. This means that the stochastic risk associated
with exposure to ionizing radiation cannot be assessed for an
individual patient. However, the concept of risk associated
with a diagnostic procedure is valid for a population of
patients, and requires, as a prerequisite, the determination of
the absorbed dose, i.e. the energy absorbed per unit mass (in
grays) in all irradiated tissues or organs of interest.
In a diagnostic context, determination of absorbed doses
(i.e. a dosimetric study) is also required before the
introduction of a new radiopharmaceutical to the market
in order to obtain marketing authorization from the relevant
agency such as the European Medicines Agency (EMA) or
the Food and Drug Administration (FDA). This also helps
to determine the range of activity to inject for a given
procedure. In addition, good clinical practice implies
injecting the minimum activity compatible with the
diagnostic purpose, and assessing the radiation exposure
delivered by that amount of activity.
Hence, the purpose of dosimetry within the context of
radiation risk assessment for diagnostic nuclear medicine
procedures is twofold:
1. Determination of reference levels of irradiation for
every new radiopharmaceutical.
For a new radiopharmaceutical, the determination of
reference levels of irradiation and consequently of the
risks associated with the administration first requires an
accurate determination of the biokinetics of the tracer.
This step is usually carried out via quantitative
imaging, blood sampling or excreta measurements in
a restricted number of patients (or healthy volunteers).
Some data are also derived from preclinical
experiments in animals. Pharmacokinetics modelling is also
often used at this stage. Then, based on the tracer
distribution in space and time, radiation dose is
calculated using phantoms, i.e. computational models
that mimic organ geometry, organ-to-organ distances,
and body composition of patients.
2. Provision of absorbed dose estimates for radiopharma
ceuticals in routine use.
The provision of absorbed dose estimates for
radiopharmaceuticals in routine use is generally a simple
task since it requires only a patient-specific
determination of the administered activity (in megabecquerels), a
task performed routinely in nuclear medicine
departments prior to injection. Then, using precalculated
tables (e.g. the ICRP reports ) that for a given
radiopharmaceutical give the absorbed dose in organs
or tissues for a reference model per injected activity (in
megabecquerels), it is possible to derive an estimate of
the absorbed dose delivered to a reference person. This
step implicitly relies on the hypothesis that the kinetic
model chosen to establish precalculated tables
satisfactorily reflects the average kinetics of the
radiopharmaceutical in subjects of interest.
Evaluation of the impact on patients health of the
administration of small amounts of radioactive substances,
or of amounts that are not or are only infrequently repeated,
as currently used in diagnostic imaging procedures, relies
heavily on a precise and accurate determination of reference
levels of irradiation, and it affects the quality of the data
used further for routine diagnostic procedures. This impact,
however, has not been addressed systematically in a
European context. Data on biokinetics and dosimetry of
these agents are reported in diverse and widespread sources
and are sometimes difficult to access. Therefore, the
European Commission addressed this issue in the
framework of the FP 7 HEALTH-2009-1.2-6 project PEDDOSE.
NET (Dosimetry and Health Effects of Diagnostic
Applications of Radiopharmaceuticals with particular emphasis
on the use in children and adolescents"). One of the main
objectives of this project is to summarize and evaluate the
current knowledge on dosimetry and the corresponding
dose-related risks when administering radiopharmaceuticals
for diagnostic purposes in children and adults.
The aim of this review is to provide detailed data on
biokinetics and dosimetry for diagnostic
radiopharmaceuticals in children and adults, and it focuses on assessing how
absorbed doses were derived.
Material and methods
Literature on the available biokinetics and dosimetry data
was systematically reviewed, mostly using PubMed (www.
ncbi.nlm.nih.gov/pubmed) and the secondary literature
cited in the articles found. Primarily, we concentrated on
radiopharmaceuticals commonly used in Europe.
The following inclusion criteria were used:
Publications of official bodies such as the International
Commission on Radiological Protection (ICRP) 
Special conference proceedings containing detailed
descriptions on methodologies in dosimetry
The literature was searched back to the publication date
of ICRP 53 (1987)  if there were no other data available.
In principle the following criteria for inclusion of data as
defined by the EANM Dosimetry Committee guidance
document on good clinical reporting  were used:
The quantitative imaging method used: planar,
SPECT(/CT) or PET(/CT), and potential corrections
(e.g. attenuation and scatter correction). The fewer
corrections the authors applied the higher was the
likelihood of increased uncertainties in the
assessment of residence times.1
The availability of data on biokinetics, in particular
detailed information on residence times and how they
were derived. Providing residence times enables a
potential recalculation and reassessment of the absorbed
doses and hence the effective dose (ED) if needed.
Organ masses can differ by more than a factor of 3 .
As a SPECT, PET, CT or MRT scan allow the
1 The term residence time has been changed in MIRD Pamphlet No.
21  to time-integrated activity coefficient.
measurement of organ volumes and therefore masses,
several studies have assumed uniform distribution of
activity and applied a first-order correction by
multiplying the activity concentration by the phantom organ
weight, resulting in normalized timeactivity curves and
& Another aspect of importance is the time-points at
which the measurements for determining the time
activity curves were made. To obtain a reliable
assessment of the area under the curve, a minimum of
three data points is recommended (MIRD 16 ) and
the time between the first and the last measurement
should not be too short, otherwise the absorbed dose
would be overestimated when using physical decay
after the last data point.
& Information on bladder voiding intervals is also crucial
because for some radiopharmaceuticals (e.g. 18F-fluoride)
the absorbed dose to the bladder depends very much on
the voiding period and the first voiding after injection;
therefore, the ED differs between datasets with different
& Detailed information on the absorbed doses to the
relevant organs and, if available, the way they were
calculated (i.e. the computer code and the source of the
S-values2) are essential, especially for a comparison of
the results. Scaling the S-values with individual organ
masses is useful for patient dosimetry in radionuclide
therapy but deviates from the usual approach for the
dosimetry of diagnostic procedures. Furthermore,
calculation of ED is not based on individual patient data.
Calculating ED according to ICRP is based on reference
values for the human body and organs .
& The tissue-weighting factors for describing the
radiation-related risk changed in 1991 with the
publication of ICRP 60 . In this work the ED was
introduced. Prior to ICRP 60 the quantity effective
dose equivalent (EDE)  was used. In 2007 the
ICRP (ICRP 103 ) published a new set of
tissueweighting factors and a new calculation method.
Therefore, when comparing EDs one has to know
which tissue weighting factors were used.
& The reliability of dosimetry data is highly dependent on
the number of participants in a study. It is important to
know the number of volunteers/patients who took part
in a dosimetry study because this affects the variability
in individual biokinetics.
In this review a summary of the most important findings
is given. Details on the available data in the references
sorted according to these criteria are given in the Electronic
2 Mean absorbed dose per unit cumulated activity, S-values are
supplementary material in Tables 1.11.4 and 2.12.6 for
adults and in Tables 3.13.4 for children. If there were no
data available, the corresponding radiopharmaceuticals are
not listed in the table. In addition, the reference values for
each radiopharmaceutical taken from the latest respective
ICRP report  are also listed in order to compare these
data with the ED or, if not available, EDE values in the
The investigated PET and non-PET radiopharmaceuticals
with and without marketing authorization are displayed in
Tables 1 and 2, respectively.
In the following sections the most important findings of
our literature search are summarized. Further details not
provided in the text are given in the corresponding tables in
the Electronic supplementary material.
As a whole-body scan with a PET scanner can take 30 min
or more (especially with older PET systems) and the uptake
of many PET radiopharmaceuticals occurs within 10 min of
injection, many studies involving the detailed measurement
of timeactivity curves are limited to scanning only one
organ per subject. Subsequently, the results of many
singleorgan measurements are merged into a virtual subject for
a complete biokinetic model and calculation of absorbed
doses. If the number of participants is large enough,
individual variations should not be important, but the small
size of many studies leads to organ data based on few
subjects. In these cases the results have to be viewed with
care, as ICRP 106  mentions in the section
Uncertainties in absorbed dose estimates that intersubject variability
may introduce considerable variation in accumulated
activity. A detailed analysis of uncertainties in internal dose
calculations for radiopharmaceuticals has also been given
by Stabin .
It is desirable that dosimetric publications include the
individual residence times, because in combination with
administered activities reanalysis of patient data is feasible
if new or different dosimetry and calculation methods
should become available . Unfortunately, most studies
omit the individual data and state only the mean values and
standard deviations, which can only provide a rough
estimate of intersubject variance.
Acetate is used in the assessment of myocardial oxidative
metabolism  and in renal, pancreatic and nasopharyngeal
Table 1 PET radiopharmaceuticals considered in this review
indicating their European marketing authorization status. No product names
are given for radiopharmaceuticals with more than one trademark
a Marketing authorization currently only in France.
b Approved by the US Food and Drug Administration (FDA)
disease . More recently 11C-acetate has become an
important tracer for imaging prostate cancer [14, 15]. The
only human study on quantitative whole-body imaging is that
by Seltzer et al.  which included six healthy male
volunteers. In this detailed study the individual residence
times in all the volunteers were determined for the important
organs, and the organ doses were calculated for the mean
values using MIRDOSE3.1 . The data were compared
with data published by the Oak Ridge Institute for Science
and Education (ORISE) in 1995 (no detailed citation
information available) which were based on a simple
threecompartment model in which all activity not measured in the
blood or excreted via the breath was assumed to reside in the
heart . The experiments were performed in dogs; activity
was measured only in the blood and expired air .
The latest ICRP report (ICRP 106 ) relies on tabulated
blood flow data for most human tissues by Leggett and
Williams . The study by Seltzer et al. , however,
was not used in ICRP 106 .
Choline is used for the imaging of prostate and brain
tumours. Roivainen et al.  showed that it is rapidly
metabolized and cleared from the blood. Tolvanen et al.
 performed a complete dosimetric study. They
compared data from normal and tumour-bearing rats and from
six patients. The rat-derived and human-derived absorbed
organ doses differed by up to a factor of approximately 6,
while the rat-derived and human-derived ED differed by a
factor of approximately 1.5.
Methionine is used in tumour diagnosis. There is only one
study on whole-body PET  which included five
volunteers and gives all relevant information for dosimetry.
This study was also used as a basis for the biokinetic model
in ICRP 106. However, the ED calculated by ICRP is 60%
higher than the one calculated by Deloar et al. .
Florbetaben is specific for beta-amyloid and is therefore
used in the diagnosis of Alzheimers disease. There is one
published study  on dosimetry that included only three
subjects and partially omitted biokinetic data. While the
authors show timeactivity curves for several organs, they
do not give residence times.
Just like 11C-choline, 18F-choline is primarily used in the
detection of prostate cancer and its metastases in bone.
Since 2010 it has had marketing authorization only in
France under the name IASOcholine; other European
countries will follow soon . Currently it is not known
if the biokinetics of 11C- and 18F-labelled choline are
different. According to Roivainen et al. , 11C-choline
is rapidly metabolized into 11C-betaine while DeGrado et
al.  have speculated that differences in blood clearance
can be explained by metabolic trapping of 18F-choline.
DeGrado et al.  compared animal and human data. As
they assumed instantaneous uptake and no biological
clearance they probably overestimated the radiation dose.
The authors did not provide biokinetic data for individual
subjects. A correction for the male organ dose has been
published as an erratum . Nosske and Brix 
developed a biokinetic model based on the available data
for humans. They assumed equal biokinetics for 11C- and
18F-choline. Janzen et al.  provided extensive data on
dosimetry; and in addition they explained their
compartment model in detail.
Zankl et al.  were mainly interested in comparing
the absorbed dose of locally absorbed electrons and
electron-specific absorbed fraction values calculated
using a Monte-Carlo method in a voxel-based
computational phantom. Therefore, the biokinetic data for a
Table 2 Non-PET radiopharmaceuticals considered in this review
indicating their European marketing authorization status. No product
names are given for radiopharmaceuticals with more than one
Authorized Not authorized
Well-established Not well-established
single patient were sufficient for the purposes of their
study, and they did not give any details about the
acquisition of the data.
DOPA is an amino acid analogue which is marketed
under the name of IASOdopa in Austria, Germany
and France. It is used in the diagnosis of several
neurological and oncological diseases. The organ doses
published in the SPC (Summary of Product
Characteristics)  were taken from addendum 4 to ICRP 53
, which has been replaced by ICRP 106 . No
pretreatment with carbidopa was assumed in the ICRP
106 report and for the dosimetric data given in the SPC.
Different biokinetics after this pretreatment have been
reported, especially for the brain and bladder . All
the studies mentioned are included in ICRP 106; no
newer literature is available.
The uptake of FDG is dependent on glucose metabolism
and can be used in the detection of fast-growing cancer
cells and inflammation. There are many studies that have
included adult subjects, but in most either no whole-body
scans were performed  or timeactivity curves were
fitted to the sum of two exponential functions to three data
points only [37, 38]. In two studies [33, 34] the experiments
were repeated in the same subjects with small intrasubject
Dowd et al.  measured urine activity only and
developed a dynamic bladder model. Deloar et al. 
used MRI to determine organ masses of their subjects and
PET for activity distribution. Using these data they
calculated residence times and absorbed doses utilizing
the MIRD phantom, the Japanese reference man and
Svalues scaled with the individual organ masses. A
dynamic bladder model was not used and they did not
provide individual data. This study was used in ICRP 106.
In another study by Deloar et al.  the authors
compared thermoluminescent dosimetry with whole-body
PET-based dosimetry and found good agreement. They did
not give individual patient data. While both studies by
Deloar et al. [37, 38] give an identical ED, they were
performed in different subjects and the organ doses vary
slightly. The authors of MIRD Dose Estimate Report No.
19  merged the data from four studies in which the
biokinetic data for specific organs were determined. This
study was used in ICRP 106.
Wu et al.  were interested in developing an improved
bladder model and therefore imaged only the bladder. They
reported absorbed doses to the bladder wall in relation to
initial bladder volume and first urine voiding time and
individual biokinetic data. Koukouraki et al.  studied
the pretherapeutic use of FDG and gave the rate constants
for a local diagnostic three-compartment model (a blood
compartment and two tissue compartments). Khamwan et
al.  imaged patients in a Thai hospital and developed a
dosimetry for Thais. Due to missing biokinetic data and
some omitted imaging details, it is difficult to evaluate the
results of their study. They used tissue weighting factors
from ICRP 103  and the S-values of the MIRD phantom
(70 kg reference man) scaled with the subjects organ
FET is an amino acid used in imaging lymphomas. Pauleit
et al.  determined the biokinetics and performed a
dosimetric assessment based on blood and urine samples
and two whole-body scans. As they did not report details
for the determination of the timeactivity curves, the results
cannot be heavily relied upon.
Sodium fluoride is a bone-seeking pharmaceutical and is
therefore used for bone scanning. In 1978 Charkes et al.
 reported the rate constants for a whole-body
fivecompartment model, which was used in ICRP 53. Since
then further research has only been performed using a
diagnostic local three-compartment model first used by
Hawkins et al. . The studies working with this model
show a wide variation in bone uptake by a factor of up to
10  depending on the location of the bone (usually
vertebrae or humerus), hydration and the diseases of the
subjects. Fluoride uptake into bone is around 50% in
healthy subjects , so diseases affecting the whole skeletal
system such as osteoporosis might significantly affect
In February 2011 fluoride was approved by the FDA, but
the dosimetric data have not been updated and in the
official FDA information EDE is still given . In Europe,
fluoride is now also available as IASOflu . In France
it was approved as early as 2008. In the French SPC there is
no recommendation given for the activity dosage in
paediatric nuclear medicine .
18F-MISO is used in imaging hypoxia. Graham et al. 
pooled the organ data obtained from 60 patients with scans
differing in field of view and scanning time. They randomly
chose a residence time from the pool for each measured
source organ, used them to calculate the absorbed doses
with S-values from MIRDOSE2 , and repeated this
1,000 times using a Monte-Carlo simulation. The resulting
median values and 25% and 75% percentiles are presented
in a table.
All 68Ga-labelled radiopharmaceuticals mentioned here are
peptide analogues that bind to somatostatin receptors, which
are often overexpressed in neuroendocrine tumours. Despite
its widespread use and ease of distribution (68Ga is eluted
from a 68Ge/68Ga radionuclide generator), the literature on
68Ga is sparse. For 68Ga-DOTANOC, a single but well done
study is available . Despite an intensive search, no
publications dealing with dosimetry for 68Ga-DOTATATE
were found. There are data only for 111In-DOTATATE and
177Lu-DOTATATE used in therapy . The pretherapeutic
use of 68Ga-DOTATOC has been studied , and Hartmann
et al.  performed a complete dosimetric study of
68GaDOTATOC, although the significance of the difference
between the reported male and female ED values seems
doubtful due to the small number of subjects.
82Rb is commercially available as CardioGen-82
(a 82Sr/82Rb generator) and is used in cardiac imaging;
it is approved by the FDA. The absorbed organ doses in
the SPC  are based on studies in rats  and only
two humans . The ICRP calculations are based on a
theoretical model of blood flow and represent worst case
conditions. Stabin  has proposed a revision to the
radiation dosimetry of 82Rb. He compared the blood-flow
model of the ICRP  with a blood-flow model proposed by
Leggett and Williams  and with the data from the two
humans . He analysed the biokinetic data using
OLINDA/EXM dose calculation software , and
concluded that the model of Leggett and Williams is most appropriate
for general use. The latter model provided an ED that was
smaller than the ICRPs worst case condition by a factor of
2. Senthamizhchelvan et al. studied the biodistribution in ten
healthy volunteers at rest  and under pharmacological
stress . The studies were methodologically correct and
well accomplished and provided new results, with the
exception of the improper use of ICRP 103 weighting factors
(see Discussion). However, in both studies [57, 58], ED
values were also calculated using the ICRP 60 weighting
factors. The calculated EDs are comparable to those obtained
by Stabin  using the data of Ryan et al. and Leggett and
Williams. However, the ED value calculated using the data of
Leggett and Williams is 50% higher than the value calculated
by Senthamizhchelvan et al., while the value calculated using
the data of Ryan et al. is 30% lower.
99mTc-antigranulocyte is a monoclonal antibody (BW 250/
183) produced in murine cells and used in determining the
location of inflammation/infection in peripheral bone in
adults with suspected osteomyelitis . It was approved
by the EMA in 2010 and is marketed under the name
Scintimun. Published data on biokinetics are available but
without residence times for calculating absorbed doses [60
62]. The biokinetic study of Buchmann et al.  evaluated
the suitability of 99mTc-anti-CD66 monoclonal antibody
BW 250/183 for myeloablative radioimmunotherapy.
No published dosimetry data were found in peer-reviewed
journals for the monoclonal antibody BW 250/183. In the core
SPC of IBA Molecular  and the core SPC of the EMA
 data on dosimetry have been included. However, in the
SPC of IBA Molecular only the organ doses and the EDE
have been given. These data contain no detailed description
of the origin of the biokinetic and dosimetric data. The same
applies to the data in the core SPC of the EMA.3 In this SPC
the organ doses were calculated for the reference man and
the reference woman separately and then the ED was
calculated using the ICRP 103  tissue weighting factors.
As noted in the discussion, ICRP 103 should not yet be used
for describing the risk of medical procedures in nuclear
Most commonly, MAA is used in lung perfusion imaging
for the diagnosis or exclusion of pulmonary emboli. The
biokinetic model adopted by ICRP 53 is the same as that
used for iodine-labelled MAA , except for the excretion
model which is replaced by the model for
99mTc-pertechnetate when a blocking agent has been given. The latest data
on quantitative imaging were published in 1983 by Malone
et al. . According to ICRP 53 , the quantitative data
on the metabolism of iodine- and technetium-labelled MAA
in the literature show discrepancies.
Pertechnetate is used in imaging the thyroid and salivary
glands, and for the diagnosis of Meckel's diverticulum.
Biokinetic data are available in ICRP 53 , and no newer
data have been published. The biokinetic model of ICRP 53
relies on data published in 1965, 1966 and 1969, and on
data published in the MIRD Dose Estimate Report No. 8 in
1976 , the latter relying on a compartment model
proposed by Hays and Berman . Smith et al. 
calculated organ doses and ED for the well-established
MIRD system of mathematical anthropomorphic phantoms
and a family of realistic voxel phantoms using the
biokinetic data published in ICRP 53 , and compared
Sestamibi is mainly used in imaging the myocardium. The
latest data found were publications that were used for the
biokinetic model in ICRP 80 by Wackers et al.  and
Leide et al. . In both studies rest and stress tests were
3 For each organ, or group of organs, the absorbed doses were
calculated using the methodology developed by MIRD (Medical
Internal Radiation Dose) 
conducted. There are significant differences in MIBI uptake
in several organs between rest and stress studies; these also
differ considerably between individual subjects .
Technegas is used in lung ventilation scintigraphy to diagnose
pulmonary embolism. It is an aerosol of ultrafine
99mTclabelled carbon particles with a particle size around 50 nm
. A summary of the biokinetics can be found in ICRP 80
, according to which a biokinetic model was developed.
None of the references in ICRP 80 provide organ doses for
organs other than the lung. The organ dose for the lung is
reported as 4.5 mSv/37 MBq . This organ dose relies on
data published in the Handbook of radiation doses in
nuclear medicine and diagnostic X-ray  to which we
were not allowed access, and hence could not assess how
this dose was calculated.
Tetrofosmin, marketed as Myoview, is used in
myocardial perfusion imaging and in imaging of the
female breast. Biokinetic and dosimetric data are
published in the latest ICRP report (ICRP 106) .
However, due to a printing error, the values in the ICRP
106 table for the resting subject and the subject under
stress are identical. The data in both tables belong to the
stress data (personal communication with a member of the
ICRP task group). Unfortunately, an erratum has never
been published by ICRP. Although the biokinetic data are
the same in ICRP 80 and ICRP 106, the absorbed doses to
the organs, and hence the ED, are slightly different in the
stress studies (probably in the rest study too, but these data
are not available). This is due to the fact that the ICRP has
changed the phantoms and the source of the S-values used
for calculating the doses. For ICRP 53 and ICRP 80 [1, 2],
a 70-kg adult male phantom was considered that was
described in MIRD Pamphlet No. 5 Revised , and
which was based on the ICRP 23  reference man. The
corresponding S-values used for absorbed dose
calculations were taken from MIRD Pamphlet No. 11 . For
children the phantoms considered were those developed
by Cristy .
For ICRP 106 , the phantoms considered were those
developed by Cristy and Eckerman  for both adult male
and children. The whole-body mass of the adult phantom of
Cristy and Eckerman changed slightly to 73.7 kg. For
absorbed dose calculations the published S-values of Stabin
and Siegel  were used.
The biokinetics are quite similar to those of sestamibi.
However, tetrofosmin is cleared more rapidly from the liver
and the absolute uptake in the heart is lower. The biokinetic
data in ICRP 80 and ICRP 106 are based on publications by
Smith et al.  and Higley et al. . Both studies were
conducted in the same hospitals (multicentre study with two
hospitals) and the same number of patients. It is not clear if
the patient groups were identical because the injected activity
differed between the studies. However, the calculated EDs
are the same in both publications. The dosimetric data
provided by GE Healthcare in the core SPC  are human
data; the source of the data, however, is not referenced.
201Tl is used in myocardial perfusion imaging. There are
discrepancies in the reported amounts of testicular
uptake of 201Tl-chloride : uptake values in the range
0.151.1% (percentage uptake at 24 h) have been reported
. In a revised dosimetry study, Thomas et al. 
performed quantitative imaging for the testes only,
shielded from the body background. They combined these
data with biokinetic data from older publications. With
these datasets for the testes the absorbed dose per
administered activity calculated in this study is less than
50% of the previously accepted value. These data have
also been included in the ICRP 106  data in
combination with the data of Krahwinkel et al. . Therefore, a
testicular uptake of 0.3% has generally been adopted
instead of 0.8% (ICRP 53  and ICRP 80 ). That is
the reason why the recalculation of the ED performed in
ICRP 106 shows a substantial decrease as compared to
ICRP 80 (0.14 mSv/MBq vs. 0.22 mSv/MBq).
Sodium Iodide is used in the evaluation of thyroid function
and/or morphology. In 2003 a refinement of the ICRP 53
biokinetic model was published by Johansson et al. . In
this compartment model the uptakes in the stomach wall and
the salivary glands were included resulting in a slight change
in the ED compared to the ED reported in ICRP 80 .
Ioflupane is a cocaine analogue used in imaging dopamine
transporters (DaT). GE Healthcare holds a marketing
authorization under the name DaTSCAN. In 1998 a
phase I biodistribution and dosimetry study was published
by Booij et al. . The residence times for several source
organs were calculated separately for each subject fitting a
multicompartment model to the timeactivity curves for
these organs. Furthermore, the absorbed doses to the organs
were calculated for each subject independently and
averaged. An erratum has been published containing a
correction of the residence time for the gallbladder content;
however, this does not affect the value of ED . The
manufacturer-provided data published in the SPC 
include absorbed doses for the target organs and the ED,
but there is no reference as to how these data were derived.
Comparing the absorbed doses and the ED given in the
SPC with the data in the paper by Booij et al.  shows
that these data were used for the SPC.
Most of the radiopharmaceuticals (except Zevalin) presented
in this section are somatostatin derivatives (see the section
about 68Ga). There is one study on 111In-DOTA-lanreotide
with complete dosimetric data  and one on therapy with
90Y  comparing DOTA-lanreotide and DOTATOC. For
111In-DOTATATE information is scarce. A single report 
presents data for blood clearance and calculated absorbed
organ doses for 90Y therapy. Two studies on 111In-DOTATOC
are available, one with absorbed organ doses and partly
omitted biokinetics  and the other with residence times
determined with a compartment model .
111In-DTPAOC (also known as DTPA-octreotide or
pentetreotide) is marketed as OctreoScan. The reports
by Bajc et al.  and Stabin et al.  contain all relevant
data for dosimetry. Two other studies [93, 94] have
considered only the pretherapeutic use of 111In-DTPAOC
and estimated biokinetic data for 90Y-DOTATOC have been
Ibritumomab, licensed as Zevalin, is an antibody that is
labelled with either 111In or 86Y for pretherapeutic imaging
or 90Y as a therapeutic agent against lymphomas. In the EU
Zevalin has marketing authorization only for therapeutic
use with 90Y. Two reports by Wiseman et al. [95, 96] present
only estimated absorbed organ doses for therapy, while
MIRD Dose Estimate Report No. 20  provides complete
biokinetic and dosimetric data for 111In-ibritumomab.
67Ga-citrate is used for localization of inflammatory lesions.
The only available biokinetic and dosimetric data were
published in the MIRD Dose Estimate Report No. 2 in
1973 . These data were used for the biokinetic model in
ICRP 53 .
Dosimetry data in paediatric nuclear medicine
In the following we present a summary of the few data
available for paediatric applications in nuclear medicine
diagnostics. Further details are given in the tables in the
Electronic supplementary material.
In general ICRP uses the same biokinetic models for
children as for adults and paediatric age-dependent
mathematical phantoms to calculate absorbed doses in children
as there is a lack of specific knowledge. According to ICRP
, it is assumed that this might lead to an overestimate
of the absorbed dose because of shorter biological
halflives in children than in adults; however, the
measurements for 99mTc-DMSA and 99mTc-HMPAO in children
show that the kinetics are not very different.
Only two publications actually present measured data for
paediatric subjects. Ruotsalainen et al.  imaged the
brain and bladder of newborns with serious neurological
symptoms. The residence times of other organs were taken
from the literature and scaled according to body and brain
mass. Then the S-values of a newborn Cristy-Eckerman
phantom  were used for calculation of absorbed doses.
They found that only 4% to 7% of injected activity is
excreted into the bladder while ICRP 106 assumes 24%.
Niven and Nahmias  examined very low birth weight
newborns with suspected lung inflammation. As these
patients were on average three times lighter than a
fullterm newborn, they scaled the S-values of the newborn
Cristy-Eckerman phantom with individual organ masses
assuming target and source organ were identical. Due to
large uncertainties, they were only able to calculate
dosimetry for three cases based on assumptions.
The review by Gelfand  includes (as do at least two
other papers [102, 103]) a table for absorbed doses of
18Ffluoride in children that claims to be derived from ICRP 53,
but the organ doses differ by up to 20%. For example, the
absorbed dose to the bladder wall of a 1-year-old child is
1.3 mSv/MBq according to Gelfand and 1.1 mSv/MBq
according to ICRP 53.
Imaging was performed in 24 children aged from 5 weeks to
14.8 years (15 normal and 9 with renal pathology). The
administered activities were scaled according to the EANM
1990 paediatric dosage card . No obvious age
dependencies in the biokinetics in children with normal renal
function were found; only children younger than 1 year
showed a reduced urinary excretion uptake . Therefore
the differences between adults and children with normal
renal function are relatively small; the adult biokinetic data
are a good approximation for all ages . Absorbed dose
calculations have also been reported by Smith et al. .
Their computer code used paediatric anthropomorphic
phantoms representing children of ages 15, 10, 5 and 1 year
weighing 55.6, 32.4, 18.6 and 9.9 kg, respectively, and a
newborn weighing 3.4 kg. The children were matched to the
closest phantom by age and weight. A second approach was
also chosen: interpolation between the organ doses calculated
with two adjacent phantoms for each child.
Vestergren et al.  evaluated the biokinetics of HMPAO in
children. Since it is very difficult to study children, especially
very young ones, only three whole-body scans were done (1,
7 and 24 h after injection). For the calculation of the absorbed
doses in children the same biokinetic models as used in adults
were used, and the age of each patient was rounded to the
closest of the ages 0, 1, 5, 10 and 15 years and adult. For
most organs no obvious age-dependent differences in the
residence times were found. There were differences only in
the brain and in the nonspecified organs .
The dosimetry data in the publication on paediatric
radiation dosimetry by Stabin et al.  rely on measured
data from only four children at different ages (8 days, and
2.5, 5 and 14 years). The authors emphasized that these
data were only preliminary and, therefore, no true
agedependency has been identified.
According to ICRP 53 (relying on data by Gelfand et al.
) the absorbed dose to the growing regions of
childrens bone is higher by a factor of 25 than assumed
for the mean absorbed dose in adults and hence the mean
absorbed dose in children using the adult biokinetics is not
likely to be considerable underestimated.
Compiling data on radiopharmaceutical dosimetry for
diagnostic nuclear medicine inevitably leads to the
question of up-to-date minimum standards for collecting
reliable data for dosimetry. In principle, the steps
described in MIRD Pamphlet No. 16 , ICRU 67
 and the EANM dosimetry guidance document on
good dosimetry reporting  should be considered.
Stateof-the-art dosimetry today includes the use of CT systems
for attenuation correction, scatter correction, consideration
of the duration of the study depending on the biokinetics
of the radiopharmaceutical and of bladder voiding
intervals, a calculation of residence times including an analysis
of the errors associated with the respective calculation
method and the appropriate use of phantoms for
calculating EDs. As the number of subjects in many biokinetic
and dosimetric studies is fewer than 10 the question of the
validity of the data for a larger population needs to be
addressed. In the scope of the new ICRP recommendations
 (ICRP 103) gender-specific differences might also
need to be considered in the future.
In some cases it was very difficult to find data on
biokinetics and dosimetry, especially for
radiopharmaceuticals that changed their name during the approval phase.
For example, it was not clear at first glance that
123IIoflupane and 123I-FP-CIT are identical. The same applies
to 99mTc-HMPAO and 99mTc-exametazime. For some
radiopharmaceuticals with marketing authorization such
as 99mTc-antigranulocyte no peer-reviewed articles
containing dosimetry data have been published; thus the
quality of the underlying experimental data cannot be
assessed. For 18F-fluoride, a more frequently used PET
radiopharmaceutical, no whole-body quantitative imaging
data are available, and the biokinetic models rely only on
compartment models (based on blood and urinary excretion)
and/or local quantitative images. For 68Ga-DOTATATE no
published data on dosimetry are available.
For some radiopharmaceuticals the biokinetic data were
acquired more than 20 years ago (e.g. 67Ga-citrate,
99mTcDMSA, 99mTc-DTPA, 99mTc-ECD, 99mTc-MAA,
99mTcpertechnetate, 99mTc-sestamibi, and 18F-fluoride). Due to
considerable improvements in nuclear medicine equipment
over the years, an improved assessment of the absorbed
doses seems warranted and would be of scientific interest.
For 201Tl-chloride, a recalculation of the absorbed doses in
ICRP 106  following reevaluation of the available data
on testicular uptake led to a substantially decreased ED
compared to ICRP 80  (11 mSv vs. 17 mSv with an
administered activity of 75 MBq).
Dosimetry data for paediatric nuclear medicine
applications of radiopharmaceuticals are sparse. In the case of
missing paediatric data, the ICRP reports use the biokinetics
obtained in adults and paediatric age-dependent mathematical
phantoms. As the size and weight of children and adolescents
vary considerably and show only a poor correlation with age,
the dose coefficients (listed in the ICRP publications) should
be adjusted according to weight instead.
The latest publication of the ICRP on absorbed doses for
radiopharmaceuticals (ICRP 106)  still applies the tissue
weighting factors given in ICRP 60 . The 2007 ICRP
recommendations (ICRP 103)  now clearly demand the
use of male and female reference voxel phantoms which were
published in ICRP 110 . The new concept demands a
determination of the equivalent doses to the organs and
tissues of the reference male and the reference female
separately. In order to obtain the equivalent doses to the
reference person, the gender-specific equivalent doses are
averaged; hence the new tissue weighting factors can be
applied. Moreover, according to ICRP 103, only the latest
ICRP voxel phantoms should be used for the calculations of
ED. Applying the new weighting factors to a set of equivalent
organ doses previously calculated with a mathematical
phantom will therefore not result in a correct ED value due
to ICRP 103. Presently, the modified tissue weighting factors
and the subsequent calculation of the ED according to the
formalism of ICRP 103 cannot be applied to nuclear
medicine as the S-values for radiopharmaceuticals using the
new recommendations of the ICRP are still missing.
As, in many cases, the dosimetry protocols applied for a
given radiopharmaceutical are very heterogeneous with
respect to the time-points and bladder voiding, and to the
dose assessment after the last data point (e.g. for
18Fcholine, 18F-FDG, 99mTc-ECD and 99mTc-HMPAO).
Therefore, the development of more uniform protocol templates
for diagnostic nuclear medicine dosimetry is required.
In many articles the description of the methodology and
the reporting of the results are incomplete so that it is
difficult to get information for reassessment of absorbed
doses. In future articles the use of the suggestions given by
the EANM guidance document on good dosimetry
reporting  is strongly recommended.
For most diagnostic radiopharmaceuticals dosimetry data
are available, although the data collection and calculation
methods are heterogeneous. As some of the data were
acquired more than 20 years ago, it would be of interest to
generate new data on biokinetics and dosimetry in
diagnostic nuclear medicine using state-of-the art
equipment and more uniform dosimetry protocols. Data for
paediatric nuclear medicine are missing in most cases.
As some of the references collected for this review are
not easily accessible a major conclusions of this work is
that, for easier public access to dosimetry data of diagnostic
radiopharmaceuticals, a database containing these data
should be created and maintained.
Acknowledgment This work was conducted within the project
PEDDOSE.NET (www.peddose.net) which is financially supported
by the European Commission under the 7th Framework Programme
FP7-Health-2009-1.2-6 (grant agreement number 241608).
This work is fully endorsed by the Dosimetry Committee of the
Conflicts of interest None.
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