**2. International guidelines in pediatric nuclear medicine (EANM, ICRP, IAEA, image gently, SNMMI, ACR)**

Paediatric applications of nuclear medicine provide invaluable information in the diagnosis and follow-up of many pathological disorders as well as in therapy.

In North America, the 'Image Gently' Campaign encouraged the formation of an expert group to overcome the lack of paediatric guidelines and to look into the possibility of developing paediatric harmonized guidelines. These guidelines were approved by the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the Society for Pediatric Radiology (SPR) and the American College of Radiology (ACR).

Although the North American and European Association of Nuclear Medicine (EANM) guidelines use different models, both have concluded in the development of a set of international guidelines, also referred to as "*Pediatric Radiopharmaceutical Administration: Harmonization Guidelines*" [1].

#### *Nuclear Medicine Dosimetry in Paediatric Population DOI: http://dx.doi.org/10.5772/intechopen.105346*

A modified version of the EANM dosage card incorporating the suggested changes is available online. Data on the biokinetics and dosimetry of commonly used radiopharmaceuticals in paediatric nuclear medicine is missing; an appreciable increase, in obtaining more and better data on image quality and biokinetics, focuses on dosimetry as a basis for further improving the recommended administered activities.

Application of the guidelines will allow many paediatric nuclear medicine patients to receive radiopharmaceutical doses lower than those that are traditionally given, resulting in an overall reduction of radiation exposure in these patients.

Paediatric patients are a particular challenge, as body size and the spatial relationships of individual organs can be very different compared to those of a typical adult.

Effective dose is a useful method for assessing the potential radiationally induced effects as a result from various practices within a population group, or more specifically to children within a similar age group, but attention should be paid used when comparing the radiation risks between the groups considering that the organ-weighting factors are averaged over both age and gender [2].

The International Commission on Radiological Protection (ICRP) has published numerous reports addressing the issue of radiation dose with respect to administrated activities in diagnostic nuclear medicine procedures. ICRP Publication 17, published in 1971 and updated in ICRP Publications 53, 80 and 106, address the absorbed dose for various used radiopharmaceuticals. In more details, these reports represent a collection of available data that may be used to estimate radiation dose, expressed as radiation dose to specified target organs, as well as the effective dose, to a population of patients to whom a specific radiopharmaceutical has been administered. They provide conversion factors for the administered activity to effective dose (in mSv/ MBq) based on models of patients of different ages, such as 1, 5, 10 and 15 years-old, as well as adults).

Efforts of standardizing and optimising administered activities of radiopharmaceuticals in paediatric nuclear medicine produced fruitful results. Two major guidelines providing administered activities recommended for children, have been developed: one in Europe and the other one in North America.

The European Association of Nuclear Medicine (EANM) issued guidelines for administered activities in children that included a dosage card which provides recommended administered activities for a variety of diagnostic nuclear medicine procedures and radioisotopes correspondingly. EANM's dosage card aim is to secure similar radiation dose levels for all patients undergoing a particular type of nuclear medicine procedure. Therefore, for each radiopharmaceutical, recommended administered activities were calculated (**Figure 1**) so that patients in various age groups receive similar estimated effective doses.

Effective Doses in paediatric PET examinations are included in the following (**Figure 2**), per age group in mSv/MBq.

The Society of Nuclear Medicine and Molecular Imaging (SNMMI) of North America, the American College of Radiology (ACR), the Society of Pediatric Radiology (SPR) and the Image Gently campaign developed also guidelines for dose optimization by identifying best practices [3]. The North American harmonic socalled guidelines are strictly weight-based for 10 out of the 12 procedures included in the guideline, with recommended administered activities corrected for patient size (expressed as mCi/kg or MBq/kg). Consequently, for each nuclear medicine procedure, these guidelines tend to result in similar levels of image noise and thus image quality, for patients of all sizes.

#### *Dosimetry*


#### **Figure 1.**

*EANM dosage card- Radiopharmaceutical activities are calculated for administration to paediatric patients by weight coefficient in all age groups. Effective doses are estimated for various diagnostic examinations.*


#### **Figure 2.**

*Effective doses in paediatric PET examinations by common PET radiopharmaceuticals for age groups 5-, 10-, and 15- (ICRP publications).*

European and North American guidelines differ due to the different models used to develop them. In addition, for some radiopharmaceuticals, there are considerable variances between the two guidelines in the reference adult administered activities, which are used in order to calculate children's activities.

Differences in the effective doses resulting between the two 'schools' were more pronounced in younger patients. For ages 1 year or 5-year olds, the EANM's administered activities result in an estimated effective dose at least 20% greater than that provided by the North American guidelines.

The critical organ is independent of the administered activity of radiopharmaceuticals. The most common critical organ is the urinary bladder. At the administered activities recommended by the two guidelines, the highest radiation absorbed doses to other critical organs are those produced by Tc99m-MDP to bone and I123-MIBG to the liver. Normal renal function is assumed when dose estimates are calculated.

#### *Nuclear Medicine Dosimetry in Paediatric Population DOI: http://dx.doi.org/10.5772/intechopen.105346*

Age-specific or disease-specific alteration in organ function can change the biokinetics of a radiopharmaceutical and thus change radiation exposure.

The ICRP allows an adjustment for abnormal renal function or for unilateral ureteral blockage when calculating the absorbed radiation dose from renal imaging agents. For example, infants with biliary atresia have an underdeveloped or absent gallbladder, so the gallbladder is unlikely to be the critical organ during a performance of hepatobiliary scintigraphy in these children.

#### **2.1 Image gently**

The Image Gently Alliance was formed to help change practice and increase awareness about radiation exposure to children by medical imaging. The effort of Image Gently Alliance was supported by SNMMI, the SPR and the ACR.

A Nuclear Medicine Working Group has assisted to *standardize* radiopharmaceutical administered activities in the practice of paediatric nuclear medicine across North America and to *harmonize* these practices with those in Europe.

The Nuclear Medicine Global Initiative project (NMGI) was formed in 2012 by 13 international organizations to promote human health by advancing the field of nuclear medicine and molecular imaging. The first project focused on the standardization of administered activities in paediatric nuclear medicine and resulted in two articles [4, 5].

Guidelines have a positive effect on the practice of many nuclear medicine departments dealing with children. Resources useful for radiation dose estimation of paediatric nuclear medicine examinations can be obtained in *Paediatric Injected Activity Tool* (SNMMI) for estimation of injected activity in children and *Nuclear Medicine Radiation Dose Tool* (SNMMI) for an approximate effective dose estimation either by ICRP185, 2015 model or by RADAR model 2017 in various paediatric nuclear medicine examinations.

## **3. Paediatric dose phantoms**

Paediatric model-derived pharmacokinetics to compare absorbed dose and effective dose estimates for F18−FDG in paediatric patients, using S values generated from two different geometries of computational phantoms; Cristy-Eckerman stylized phantoms (C−E) and University of Florida/National Cancer Institute (UF/NCI) hybrid computational phantoms.

Time−integrated activity coefficients of F18−FDG in brain, lungs, heart wall, kidneys and liver, retrospectively, were calculated. The absorbed dose calculation was performed in accordance with the Medical Internal Radiation Dose (MIRD) method using S values generated from the UF/NCI hybrid phantoms. The effective dose was computed using tissue−weighting factors from ICRP publication 60 and 103 for the C−E and UF/NCI, respectively.

Differences in anatomical modelling features among computational phantoms used to perform Monte Carlo−based photon and electron transport simulations for F18, effect internal organ dosimetry computations for paediatric nuclear medicine studies.

Paediatric pharmacokinetic data are collected for diagnostic imaging agents, relevant to paediatric studies and the field conversions from older stylized phantoms to more detailed computation hybrid phantoms were created. The effective doses,

computed by the UF/NCI hybrid phantom S values, were different than those seen using the C−E stylized phantoms for newborns, 1-year-old and 5 years old, **Figures 3** and **4** [6].

Since hermaphrodite *Cristy-Eckerman* phantoms are used to represent the newborn, 1-year-old and 5-year-old anatomies, the OLINDA/EXM (*Organ Level INternal Dose Assessment/EXponential Modelling*) code developed by the Radiation Dose Assessment Resource (RADAR) Task Group of the Society of Nuclear Medicine, output for these age groups provides organ−absorbed doses for both paediatric male and female tissues.

In contrast, the University of Florida hybrid phantoms are gender-specific and these tissues are specifically modelled age-wise. The dose estimates for breast and ovaries obtained by the University of Florida F/NCI hybrid phantom were higher for newborn, 1-year-old and 5-year-old ages. The effective dose coefficient computed by OLINDA/EXM version 1.0 uses an effective dose coefficient that is based on radiation and tissue weighting factors specified in ICRP Publication 60 (1991). Later publication 103 (2007), readjusted the tissue weighting factor for breast from 0.05 to 0.12 and for gonads from 0.20 to 0.08.

The understanding of transitioning from the older phantoms and tissue−weighting factors to the most recently updated phantoms that are now being adopted by ICRP is essential (OLINDA/EXM version 2.0).

The OLINDA/EXM has standardized dose calculations for diagnostic and therapeutic radiopharmaceuticals. The previous generation of anthropomorphic phantoms based on the Oak Ridge models, employed geometrical shapes in order to define the body and its organs.

Nowadays, these models have been replaced with realistic, Non-Uniform Rational B-Spline (NURBS) type models based on the recent standardized masses defined by the ICRP in its Publication 89. NURBS is a mathematical model using B-splines that is commonly used in computer graphics for representing curves and surfaces.

These and other new models have been implemented in a new version of the OLINDA/EXM 2 code. The new generation of models is now available in the

**Figure 3.** *Three-D visualization of Cristy-Eckerman (C-E) stylized phantoms [6].* *Nuclear Medicine Dosimetry in Paediatric Population DOI: http://dx.doi.org/10.5772/intechopen.105346*

**Figure 4.**

*Three-D visualization of University of Florida/National Cancer Institute (UF/NCI) hybrid computational phantoms for various age groups [6].*

OLINDA/EXM code and represents a significant improvement in standardized dose calculations. OLINDA/EXM version 2.0 employs realistic NURBS-style phantoms [7].

ICRP in Publication 143, Paediatric Computational Reference Phantoms, 2020, has adopted a set of reference phantoms that were derived from the University of Florida phantoms. ICRP phantoms will be used to calculate ICRP dose coefficients. The publication is supported by a series of annexes. The last annex gives a description of the electronic files available for download and use of each of the 10 paediatric reference computational phantoms.

A reference set of phantoms and dose coefficients for external exposures and intakes of radionuclides will promote consistency in the assessment of doses.
