Abstract
Editor-in-Chief
C.H. CLEMENT
Associate Editor
H. FUJITA
Authors on behalf of ICRP
A. Giussani, S. Mattsson, M. Andersson, L. Johansson, D. Nosske
1. INTRODUCTION
(1) In 2015, the International Commission on Radiological Protection (ICRP) published a compendium of the calculations of organ absorbed dose and effective dose equivalent per unit activity administered (Publication 128, ICRP, 2015) for a number of radiopharmaceuticals used in diagnostic nuclear medicine. Publication 128 put together and, when necessary, updated the information already presented in previous reports, namely Publication 53 ‘Radiation dose to patients from radiopharmaceuticals’ (ICRP, 1988) and its addendums: Addendum 1, included in Publication 62 (ICRP, 1992); Addendum 2, issued as Publication 80 (ICRP, 1998); Addendum 3, issued as Publication 106 (ICRP, 2008); and Addendum 4, available online (ICRP, 2014).
(2) One of the tasks of ICRP Task Group 36 ‘Radiation dose to patients in diagnostic nuclear medicine’ is the publication of models and dose coefficients for new radiopharmaceuticals on the website. This addendum is the first amendment of Publication 128 (ICRP, 2015) providing biokinetic models, absorbed doses, and effective doses per unit activity for the following two radiopharmaceuticals: 11C-Pittsburgh compound B (11C-PiB) and 68Ga-high-affinity DOTATATE (HA-DOTATATE). This addendum is also being released through the ICRP website to make the results available to users as soon as possible.
1.1. References
ICRP, 1988. Radiation dose to patients from radiopharmaceuticals. ICRP Publication 53. Ann. ICRP 18(1–4).
ICRP, 1992. Radiological protection in biomedical research. ICRP Publication 62. Ann. ICRP 22(3).
ICRP, 1998. Radiation dose to patients from radiopharmaceuticals (addendum to ICRP Publication 53). ICRP Publication 80. Ann. ICRP 28(3).
ICRP, 2008. Radiation dose to patients from radiopharmaceuticals. ICRP Publication 106. Ann. ICRP 38 (1–2).
ICRP, 2014. Radiation dose to patients from radiopharmaceuticals. A fourth addendum to ICRP Publication 53. Available at: http://www.icrp.org/docs/Radiation%20Dose%20to%20Patients%20from%20Radiopharmaceuticals%20-%20A%20fourth%20addendum%20to%20ICRP%20Publication%2053.pdf (last accessed 25 May 2020).
ICRP, 2015. Radiation dose to patients from radiopharmaceuticals: a compendium of current information related to frequently used substances. ICRP Publication 128. Ann. ICRP 44(2S).
2. 11C-Pittsburgh Compound B
2.1. Biokinetic model
(3) The compound {N-methyl-[11C]}2-(4'-methylaminophenyl)-6-hydroxybenzothiazole [Pittsburgh compound B (PiB)] is a beta-amyloid tracer for assessing brain amyloidosis, used primarily for diagnosis of Alzheimer's disease. The biokinetics of this substance have been studied in humans by Scheinin et al. (2007) and O'Keefe et al. (2009). In addition, animal studies of the biodistribution have been performed [e.g. on baboons by Parsey et al. (2005)]. The model adopted here is based solely on human data. The highest absorbed dose is, according to studies on humans, received by the gallbladder wall, liver, urinary bladder wall, and kidneys.
(4) PiB injected intravenously is assumed to be distributed rapidly in the body, with a considerable fraction of the activity located initially in the liver. Elevated concentrations are also found in the kidneys, brain, colon, and bone. Uptake in vertebral bone is reported by Scheinin et al. (2007), interpreted by the authors as localisation in cortical bone. Uptake in the skeleton of 7% is adopted here, with distribution in cortical and trabecular bone surfaces.
(5) Significant uptake in the colon has been noted by Scheinin et al. (2007), whereas O'Keefe et al. (2009) reported lower uptake, as seen in the diagnostic images. For the dose calculations based on the biokinetic data given in Table 2.1, uptake of 2% in the colon is adopted. Assuming a 50/50 distribution between upper and lower large intestine contents. Blomquist et al. (2008) reported increased uptake in the cortical brain area in patients with Alzheimer's disease. This increased uptake will slightly affect the absorbed dose to the brain. The effective dose, however, will only be affected to an insignificant degree, and this pathological variation is therefore not further considered for dose estimation.
(6) On the basis of the biokinetic data given in Table 2.1 half of the activity in the liver is assumed to stay with a biological half-time which is much longer in comparison with the physical half-time (20.4 min) and is therefore set to ∞. The other half is assumed to be transferred to the gallbladder with a half-time of 1 h. This deviates from the normal model for excretion of activity in the bile (ICRP, 2015), in which activity is also transferred directly from the liver to the small intestine. Similarly to liver, the fractions of activity present in the upper and lower large intestine are assumed to stay with a biological half-time which is much longer in comparison with the physical half-time (20.4 min) and is therefore set to ∞.
(7) For the kidneys, brain, and remaining tissues with a biological half-time of 1 h, excretion via the urinary bladder is assumed. The effective dose and the absorbed dose per unit activity administered are presented in Table 2.2.
2.2. References
Blomquist, G., Engler, H., Nordberg, A., et al., 2008. Unidirectional influx and net accumulation of PIB. Open Neuroimag. J. 2, 114–125.
ICRP, 2015. Radiation dose to patients from radiopharmaceuticals: a compendium of current information related to frequently used substances. ICRP Publication 128. Ann. ICRP 44(2S).
O'Keefe, G.J., Saunder, T.H., Ng, S., et al., 2009. Radiation dosimetry of β-amyloid tracers 11C-PiB and 18F-BAY94-9172. J. Nucl. Med. 50, 309–315.
Parsey, R.V., Sokol, L.O., Bélanger, M-J., et al., 2005. Amyloid plaque imaging agent [C-11]-6-OH-BTA-1: biodistribution and radiation dosimetry in baboon. Nucl. Med. Commun. 26, 875–880.
Scheinin, N.M., Tolvanen, T.K., Wilson, I.A., et al., 2007. Biodistribution and radiation dosimetry of the amyloid imaging agent 11C-PIB in humans. J. Nucl. Med. 48, 128–133.
3. 68Ga-High-Affinity DOTATATE
3.1. Biokinetic model
(8) Gallium-68-labelled DOTA-3-iodo-Tyr3-Thr8-octreotide analogues, termed ‘high-affinity DOTATATEs (HA-DOTATATEs)’, have proved to have superior binding characteristics compared with other 68Ga-labelled somatostatin analogues (Schottelius et al., 2015), and have been recommended as substitutes (Brogsitter et al., 2013, 2014).
(9) Hartmann et al. (2014) published a detailed investigation of the biodistribution and radiation dosimetry of 68Ga-HA-DOTATATE in seven male patients. Blood activity curves in blood, liver, spleen, adrenals, and kidneys, as well as calculated values of the time-integrated activities (cumulated activities), are given here.
(10) Based on the above data, the biokinetic model in Table 3.1 assumes that clearance from blood has two components with half-times of 0.83 min (60%) and 7 min (40%). The first component is distributed to the kidneys (5%), liver (15%), spleen (4.4%), red marrow (1.9%), adrenals (0.08%), and rest of the body (28.62%), and the remaining 5% is excreted by the renal system according to the kidney–bladder model (renal transit time 5 min). The second component is distributed to the liver (12%), spleen (3.6%), red marrow (1.6%), adrenals (0.07%), and rest of the body (22.73%). Once taken up by the organs and tissues, the activity is considered to stay there indefinitely. The effective dose and the absorbed dose per unit activity administered are presented in Table 3.2.
(11) This model is not applicable to 68Ga-DOTATATE.
3.2. References
Brogsitter, C., Schottelius, M., Zöphel, K., et al., 2013. Twins in spirit: DOTATATE and high-affinity DOTATATE. Eur. J. Nucl. Med. Mol. Imaging 40, 1789.
Brogsitter, C., Zöphel, K., Hartmann, H., et al., 2014. Twins in spirit part II: DOTATATE and high-affinity DOTATATE – the clinical experience. Eur. J. Nucl. Med. Mol. Imaging 41, 1158–1165.
Hartmann, H., Freudenberg, R., Oehme, L., et al., 2014. Dosimetric measurements of 68Ga-high affinity DOTATATE. Twins in spirit part III. Nuklearmedizin 53, 211–216.
Schottelius, M., Šimeček, J., Hoffmann, F., et al., 2015. Twins in spirit – episode I: comparative preclinical evaluation of [68Ga]DOTATATE and [68Ga]HA-DOTATATE. EJNMMI Res. 5, 22.
4. ACKNOWLEDGEMENTS
F s , fractional distribution to organ or tissue S; T (h), biological half-time for an uptake or elimination component; a, fraction of Fs taken up or eliminated (−) with the corresponding half-time; Ãs/A0 (h), cumulated activity in organ or tissue S per unit of administered activity.
Absorbed doses for 11C-Pittsburgh compound B.
The physical half-life of 11C is 20.39 min
Biokinetic data for 68Ga-high-affinity DOTATATE.
F s , fractional distribution to organ or tissue S; T (h), biological half-time for an uptake or elimination component; a, fraction of Fs taken up or eliminated (−) with the corresponding half-time; Ãs/A0 (h), cumulated activity in organ or tissue S per unit of administered activity.
Absorbed doses for 68Ga high-affinity DOTATATE.
The physical half-life of 68Ga is 68.06 min.