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2016 Update of the North American Consensus

Guidelines for Pediatric Administered
Radiopharmaceutical Activities
S. Ted Treves, MD, Harvard Medical School/Brigham and Women’s Hospital, Boston, MA; Michael J. Gelfand, MD,
Cincinnati Children’s Hospital, Cincinnati, OH; Frederic H. Fahey, DSc, Harvard Medical School/Boston Children’s
Hospital, Boston, MA; and Marguerite T. Parisi, MD, MS, Seattle Children’s Hospital, Seattle, WA

ediatric nuclear medicine provides important clinical maceuticals used in children. In patients older than 1 year,

P information in the care of children. Although nuclear

medicine techniques have been in use in adults for
more than half a century, with well-established standards
administered dose variability ranged from a factor of 3 to a
factor of 10. However, in children younger than 1 year,
this variability ranged by a factor of 10 and, in 1 case, by a
for radiopharmaceutical administered activities, this has not factor of 20 (2).
been the case for the pediatric population. As pediatric After the publication of this survey, the Image Gently
nuclear medicine grew in use practitioners faced with im- Alliance, the SNMMI, and the Society for Pediatric Radiology
aging children used a number of methods to select admin- endorsed the formation of an expert group to develop consen-
istered activities. For the most part, pediatric administered sus guidelines on pediatric radiopharmaceutical administered
activities were influenced by varying combinations of tra- doses. The inherent aim was to reduce the large variability
dition, existing dosage schedules, age of available equip- of administered doses, which in turn could have the effect of
ment, practitioner preference, and direct extrapolation from reducing overall pediatric radiation exposures. This group
adult administered activities An informal survey in 2009 produced the 2010 North American Consensus Guidelines
showed that only 4 of 22 radiopharmaceutical package inserts for Pediatric Radiopharmaceutical Administered Doses (3,4).
provided recommended pediatric administered doses (1). In- Both similarities and differences between the European and
stead, package inserts included the “orphan statement”: the North American guidelines were evident (5); these were
“Radiopharmaceuticals should be used only by physicians harmonized in 2014 (6–8).
who are qualified by training and experience in the safe use The original North American guidelines included recom-
and handling of radionuclides and whose experience and mendations for 12 radiopharmaceutical applications. Follow-
training have been approved by the appropriate government ing expert consensus workshops at SNMMI Annual Meetings,
agency authorized to license the use of radionuclides.” additional radiopharmaceuticals were included: 99mTc-HMPAO
Radionuclide imaging in children was initially limited and 99mTc-Ceretec for brain imaging, 99mTc-sestamibi and
to those patients with proven oncologic disorders, mainly 99mTc-tetrofosmin for myocardial perfusion imaging, 123I-NaI

for diagnosis of extent of disease and to evaluate for metas- for thyroid imaging, 99mTc-red blood cells for blood pool
tases. This limited use was the result of radiation exposure imaging, 99mTc-white blood cells for infection imaging, and
concerns with older radiopharmaceuticals with long half- 68Ga-DOTATOC and 68Ga-DOTATATE for neuroendocrine tu-

lives and relatively high emission energies, low photon flux, mor imaging. A table with these additions and updates is
b particle emissions, and unfavorable imaging characteris- now available (Table 1, facing page) and is available in a
tics. In addition, imaging equipment required long acquisi- poster format from SNMMI and the Image Gently Alliance.
tion times and produced images with poor spatial resolution. Publication and dissemination of this information has
With the development of short-lived radiopharmaceuticals had a positive effect in the practice of pediatric nuclear
and much lower radiation exposures, as well as the introduc- medicine. Recent surveys have indicated that a large
tion of modern equipment, pediatric nuclear medicine ex- fraction of those familiar with the guidelines have altered
panded to include evaluation of physiology, benign disorders, their practice in pediatric nuclear medicine to become more
and nononcologic diseases. With this expansion and the in- compliant (9,10). Therefore, it is apparent that further dis-
troduction of novel tracers, identification and dissemination semination of the guidelines is needed. The development of
of appropriate administered doses took on new importance. these guidelines for pediatric administered radiopharma-
Early methods of calculating doses included the Clark ceuticals has filled a long-standing need. It is important to
rule, the Young rule, the area method, and the Webster rule. consider that these guidelines should continue to be refined
However, these methods provided a very wide range of by more experience and new scientific work and that new
recommendations. No consensus among practitioners pro- procedures should be added to the guidelines as they be-
vided dose standards. A 2008 survey of 13 North American come more routinely available in children. There is a need
pediatric nuclear medicine clinics revealed a wide range for more data on radiopharmaceutical biodistribution and
of administered radiopharmaceutical activities in children. biokinetics in children—data that at present are quite scarce
The survey examined 16 of the most common radiophar- or nonexistent. Sophisticated phantom modeling for children

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TABLE 1
2016 Update: North American Consensus Guidelines for Pediatric Administered Radiopharmaceutical Activities1

Minimum
Administered administered Maximum administered
Radiopharmaceutical Notes activity activity activity

123I-MIBG [A] 5.2 MBq/kg 37 MBq (1.0 mCi) 370 MBq (10.0 mCi)
(0.14 mCi/kg)
99mTc-MDP [A] 9.3 MBq/kg 37 MBq (1.0 mCi)
(0.25 mCi/kg)
18F-FDG [A, B] Body: 3.7-5.2 MBq/kg 26 MBq (0.7 mCi)
(0.10–0.14mCi/kg)
Brain: 3.7 MBq/kg 14 MBq (0.37 mCi)
(0.10 mCi/kg)
99mTc-DMSA [A] 1.85 MBq/kg 18.5 MBq (0.5 mCi) 100 MBq (2.7 mCi)
(0.05 mCi/kg)
99mTc-MAG3 [A, C] Without flow study: 37 MBq (1.0 mCi) 148 MBq (4.0 mCi)
3.7 MBq/kg
(0.10 mCi/kg)
[A] With flow study:
5.55 MBq/kg
(0.15 mCi/kg)
99mTc-IDA [A, D] 1.85 MBq/kg 18.5 MBq (0.5 mCi)
(0.05 mCi/kg)
99mTc-MAA [A] If 99mTc used for
ventilation:
2.59 MBq/kg
(0.07 mCi/kg)
[A] No 99mTc ventilation 14.8 MBq (0.4 mCi)
study: 1.11 MBq/kg
(0.03 mCi/kg)
99mTc-pertechnetate [A] 1.85 MBq/kg 9.25 MBq (0.25 mCi)
(Meckel diverticulum (0.05 mCi/kg)
imaging)
18F-sodium fluoride [A] 2.22 MBq/kg 14 MBq (0.38 mCi)
(0.06 mCi/kg)
99mTc (for cystography) [E] No weight-based No more than 37 MBq No more than 37 MBq
dose (1.0 mCi) for each (1.0 mCi) for each
bladder filling cycle bladder filling cycle
99mTc-sulfur colloid (for [F] No weight-based 9.25 MBq (0.25 mCi) 37 MBq (1.0 mCi)
oral liquid gastric dose
emptying)
99mTc-sulfur colloid [F] No weight-based 9.25 MBq (0.25 mCi) 18.5 MBq (0.5 mCi)
(for solid gastric dose
emptying)
99mTc-HMPAO 11.1 MBq/kg 185 MBq (5 mCi) 740 MBq (20 mCi)
(Ceretec)/99mTc-ECD (0.3 mCi/kg)
(Neurolite) for brain
perfusion
99mTc-sestamibi 5.55 MBq/kg 74 MBq (2 mCi) 370 MBq (10 mCi)
(Cardiolite)/99mTc- (0.15 mCi/kg)
tetrofosmin (Myoview)
for myocardial
perfusion (single scan
or first of 2 scans,
same day)

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TABLE 1 (Continued )

Minimum
Administered administered Maximum administered
Radiopharmaceutical Notes activity activity activity

99mTc-sestamibi 16.7 MBq/kg 222 MBq (6 mCi) 1,110 MBq (30 mCi)
(Cardiolite)/99mTc- (0.45 mCi/kg)
tetrofosmin (Myoview)
for myocardial perfusion
(second of 2 scans,
same day)
Na123I for thyroid 0.28 MBq/kg 1 MBq (0.027 mCi) 11 MBq (0.3 mCi)
imaging (0.0075 mCi)
99mTc-pertechnetate for 1.1 MBq/kg 7 MBq (0.19 mCi) 93 MBq (2.5 mCi)
thyroid imaging (0.03 mCi/kg)
99mTc-RBC for blood pool 11.8 MBq/kg 74 MBq (2 mCi) 740 MBq (20 mCi)
imaging (0.32 mCi/kg)
99mTc-WBC for infection 7.4 MBq/kg 74 MBq (2 mCi) 555 MBq (15 mCi)
imaging (0.2 mCi/kg)
68GA-DOTATOC or 68Ga-DOTATATE (18) [G] 2.7 MBq/kg 14 MBq (0.38 mCi) 185 MBq (5 mCi)
(0.074 mCi/kg)

NOTES: This information is intended as a guideline only. Local practice may vary depending on patient population, choice of collimator,
and specific requirements of clinical protocols. Administered activity may be adjusted when appropriate by order of the nuclear medicine
practitioner. For patients who weigh .70 kg, it is recommended that the maximum administered activity not exceed the product of the
patient’s weight (kg) and the recommended weight-based administered activity. Some practitioners may choose to set a fixed maximum
administered activity equal to 70 times the recommended weight-based administered activity, expressed as MBq/kg or mCi/kg (for
example, ∼10 mCi [370 MBq] for 18F-FDG body imaging). The administered activities assume use of a low-energy high-resolution
collimator for 99mTc radiopharmaceuticals and a medium-energy collimator for 123I-MIBG. Individual practitioners may use lower admin-
istered activities if their equipment or software permits them to do so. Higher administered activities may be required in selected patients.
No recommended administered activity is given for intravenous 67Ga-citrate; intravenous 67Ga-citrate should be used very infrequently and
only in low doses. [A] The EANM Dosage Card 2014 version 2 administered activity may also be used. [B] The low end of the dose range
should be considered for smaller patients. Administered activity may take into account patient mass and time available on the PET scanner.
The EANM Dosage Card 2014 version 2 administered activity may also be used. [C] Administered activities assume that image data are
reframed at 1 min/image. Administered activity may be reduced if image data are reframed at a longer time per image. [D] A higher
administered activity of 1 mCi may be considered for neonatal jaundice. [E] 99mTc-sulfur colloid, 99mTc-pertechnetate, 99mTc-DTPA, or
possibly other 99mTc radiopharmaceuticals may be used. There is a wide variety of acceptable administration and imaging techniques for
99mTc cystography, many of which will work well with lower administered activities. An example of appropriate lower administered

activities is found in the 2014 revision of the EANM Paediatric Dose Card 2. [F] The administered activity may be based on patient weight
or on the age of the child. [G] The administered activity is based on the EANM Dosage Card 2014 version 2 dosage for a 60-kg patient,
using the minimum and maximum doses from the EANM Dosage Card. There was little experience with this radiopharmaceutical in
children in North America at the time of preparation of this dosage table.

based on sex and body size should help produce better esti- PhD; Michael G. Stabin, PhD; Adam Alessio, PhD; Arturo
mates of radiation absorbed doses (11–13). The application Chiti, MD; Zvi Bar-Sever, MD; Thomas Pfluger, MD; Ronald
of advanced image processing software both for planar im- Boellaard, PhD; Lise Borgwardt, MD, PhD; Joanne F. Louis,
aging, as well as for SPECT, can help to reduce levels of CNMT; Royal T. Davis, CNMT; Gary Levine, MD; David
administered doses while preserving (and in some cases Levin, MD; Kimberly E. Applegate, MD, MS; Marta Hernanz
improving) diagnostic image quality (14–17). Schulman, MD; Daniel W. Young, MD; Victor J. Seghers, MD,
PhD; Gerald A. Mandell, MD; J. Bradley Wyly, MD; Karen
Schmitt; Ruth Lim, MD; Lisa J. States, MD; Sue C. Kaste, DO;
ACKNOWLEDGMENTS
Susan Alexander; Rebecca Maxey; Larry Binkowitz, MD;
The authors wish to acknowledge the following individuals Barry Shulkin, MD; and many others.
for participation in the process of generating the guidelines:
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In Memoriam: Robert W. Frelick, MD, 1920–2016

obert W. Frelick, MD, a prominent Delaware physi- at the University of Delaware (Wilmington), Temple

R cian whose practice focused on oncology and in-

cluded early work in nuclear medicine, died on
September 1. He received his medical degree as a captain in
University (Philadelphia, PA), and Jefferson Medical
College (Philadelphia, PA). He published hundreds of
articles and commentary in the peer-reviewed litera-
the U.S. Army from Yale University (New Haven, CT) in ture. Well into his 90s, he continued to provide med-
1944. He completed his internship at New Haven Hospital ical advice and assistance to family and friends,
(CT), and was then stationed in Germany from 1945 to volunteered at the Claymont Clinic (DE), and partic-
1947. On his return, he completed residency programs at ipated in grand rounds and medical meetings at Christi-
Memorial Wilmington (DE) and at Memorial Sloan–Kettering ana Hospital (Newark, DE) and the Helen F. Graham
(New York, NY). From 1950 to 1982 he maintained a pri- Cancer Center (Newark), which he helped to found.
vate practice in Deerhurst, DE, which included routine Dr. Frelick was an active participant in numerous
house calls. During the same period, from 1952 to 1970, professional groups including the American Medical
he served at the Wilmington Medical Center as the Director Association, the Medical Society of Delaware (presi-
of Nuclear Medicine and as a consultant in medical oncol- dent, 1980–1981), the American Society of Clinical
ogy in hospitals in Delaware and New Jersey. From 1982 Oncology, ACCC (president, 1979–1980, and board
to 1987, he was at the National Cancer Institute (NCI; of trustees, 1974–1982), and the American School
Bethesda, MD), where he was program director of the nation- Health Association. He served as a volunteer with
wide Association of Community Cancer Centers (ACCC). CARE Medico in Kabul, Afghanistan, in 1978 and later
He represented NCI as a member of the Commission on served on the CARE Executive Committee from 1986 to
Cancer of the American College of Surgeons. In 1987 he 1991. He was also an active community volunteer.
became Director of Chronic Diseases for the State of Del- In reporting on his death, the ACCC noted that
aware and medical director of the South Jersey Regional “Dr. Frelick worked to expand and improve access to
Cancer Center. He also served as a surveyor for the Amer- cancer care and clinical trials, not only in his home state
ican College of Surgeons and traveled the country evaluat- of Delaware, but throughout the country.” He is survived
ing cancer programs at community hospitals. He was a by his wife of 72 years and 5 children, 9 grandchildren,
lecturer, assistant professor, and honorary clinical professor and 5 great-grandchildren.

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