Radiation Dose to Patients from Radiopharmaceuticals: a Compendium of Current Information Related to Frequently Used Substances.

This report provides a compendium of current information relating to radiation dose to patients, including biokinetic models, biokinetic data, dose coefficients for organ and tissue absorbed doses, and effective dose for major radiopharmaceuticals based on the radiation protection guidance given in Publication 60(ICRP, 1991). These data were mainly compiled from Publications 53, 80, and 106(ICRP, 1987, 1998, 2008), and related amendments and corrections. This report also includes new information for 82Rb-chloride, iodide (123I, 124I, 125I, and 131I) and 123I labeled 2ß-carbomethoxy 3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FPCIT).The coefficients tabulated in this publication will be superseded in due course by values calculated using new International Commission on Radiation Units and Measurements/International Commission on Radiological Protection adult and paediatric reference phantoms and Publication 103 methodology (ICRP,2007). The data presented in this report are intended for diagnostic nuclear medicine and not for therapeutic applications.

An internal radiation dosimetry computer program, IDAC 2.0, for estimation of patient doses from radiopharmaceuticals.

The internal dosimetry computer program internal dose assessment by computer (IDAC) for calculations of absorbed doses to organs and tissues as well as effective doses to patients from examinations with radiopharmaceuticals has been developed. The new version, IDAC2.0, incorporates the International Commission on Radiation Protection (ICRP)/ICRU computational adult male and female voxel phantoms and decay data from the ICRP publication 107. Instead of only 25 source and target regions, calculation can now be made with 63 source regions to 73 target regions. The major advantage of having the new phantom is that the calculations of the effective doses can be made with the latest tissue weighting factors of ICRP publication 103. IDAC2.0 uses the ICRP human alimentary tract (HAT) model for orally administrated activity and for excretion through the gastrointestinal tract and effective doses have been recalculated for radiopharmaceuticals that are orally administered. The results of the program are consistent with published data using the same specific absorption fractions and also compared with published data from the same computational phantoms but with segmentation of organs leading to another set of specific absorption fractions. The effective dose is recalculated for all the 34 radiopharmaceuticals that are administered orally and has been published by the ICRP. Using the new HAT model, new tissue weighting factors and the new adult computational voxel phantoms lead to an average effective dose of half of its earlier estimated value. The reduction mainly depends on electron transport simulations to walled organs and the transition from the stylised phantom with unrealistic interorgan distances to more realistic voxel phantoms.

External radiation exposure of personnel in nuclear medicine from 18F, 99mTC and 131I with special reference to fingers, eyes and thyroid.

The radiation exposure of fingers, thyroid and eyes of workers handling radiopharmaceuticals during various nuclear medicine procedures was measured using thermoluminescent dosemeters. Dosemeters were placed on the finger tips of 19 workers on several different occasions for various procedures. Additionally, the routinely determined whole-body doses to various groups of workers were analysed. The finger dose measurements demonstrated clear differences between the various tasks, from 0.0012 µGy MBq(-1) (unpacking and installing (99)Mo/(99m)Tc-generator) to 3.0 µGy MBq(-1) (syringe withdrawal, injection and waste handling of (18)F-FDG). As long as the worker was handling (99m)Tc, the dose to the fingers was well below the ICRP dose limits, even when the activity was high. Special concern should, however, be devoted to the handling of (18)F, since the dose to the fingers could easily reach the dose limits. The estimated dose to eyes and thyroid was well below the dose limits. Since the introduction of the positron emission tomography/computed tomography facility, the annual whole-body dose has increased for those directly involved in the handling of (18)F. The annual whole-body dose of 0.2-2.5 mGy was, however, well below the dose limits.

Absolute quantification of activity content from PET images using the Philips Gemini TF PET/CT system.

Positron emission tomography combined with computed tomography (PET/CT) is a quantitative technique suitable for diagnostics and uptake measurements. The quantitative results can be used for the purpose of the calculating absorbed dose to patients undergoing nuclear medicine investigations. Hence, the accuracy of the quantification of the activity content in organs or tissues is of great importance. When using a planar gamma camera and single photon emission computed tomography (SPECT) images, the activity content in organs and tumours has to be determined by the user, using the number of counts in the organs and the efficiency of the camera. However, when using a Philips Gemini TF PET/CT system, the activity concentration in a region of interest (ROI) is given by the system. The reliability of activity concentration values given by the Philips Gemini TF PET/CT system was studied using a Jaszczak phantom containing hot spheres of different sizes; the influence of the ROI size and the impact of organ size, that is the partial volume effect, was investigated with three different lesion-to-background ratios in the phantom. The use of a small ROI size (40 % of the large ROI size, which covered the entire sphere) showed a 15 % improvement in the recovery of the true activity. Small lesion sizes result in large underestimations of the activity concentration values.

Radiation exposure of patients and personnel from a PET/CT procedure with 18F-FDG.

The positron emission tomography (PET)/computed tomography (CT) camera is a combination of a PET camera and a CT. The image from the PET camera is based on the detection of radiation that is emitted from a radioactive tracer, which has been given to the patient as an intravenous injection. The radiation that is emitted from the radioactive tracer is more energetic than any other radiation used in medical diagnostic procedures and this requires special radiation protection routines. The CT image is based on the detection of radiation produced from an X-ray tube and transmitted through the patient. The radiation exposure of the personnel during the CT procedure is generally very low. Regarding radiation exposure of the patient, it is important to notice whether a CT scan has been performed prior to the PET/CT in order to avoid any unnecessary irradiation. The total effective dose to the patient from a PET/CT procedure is approximately 10 mSv. The major part comes from internal irradiation due to radiopharmaceuticals within the patients (e.g. (18)F-FDG: approximately 6-7 mSv), and a minor part is due to the CT scan (low-dose CT scan: approximately 2-4 mSv). If a full diagnostic CT investigation is performed, the effective dose may be considerably higher. If the patient is pregnant, a PET/CT procedure should be avoided or postponed, unless it is vital for the patient. An interruption in breastfeeding is not necessary after a PET/CT procedure of the nursing mother. Close contact between the patient and a small child should however be avoided for a couple of hours after the administration of the radiopharmaceutical. The radiation dose to the personnel arises mainly due to handling of the radiopharmaceuticals (syringe withdrawal, injection, waste handling, etc.) and from close contact to the patient. This radiation dose can be limited by using the inverse-square law, i.e. by using the fact that the absorbed dose decreases substantially with increasing distance between the radiation source and the personnel.

A generic model for 11C labelled radiopharmaceuticals for imaging receptors in the human brain.

A large number of radiopharmaceuticals labelled with 11C (half-time 0.340 h) are being developed for positron emission tomographic studies of different types of receptor in the human brain. For most of these agents, the available biokinetic data are insufficient to construct realistic compound-specific biokinetic models for calculating the internal radiation dose delivered to persons undergoing investigation. A generic model for brain receptor substances that predicts the internal dose with sufficient accuracy for general radiation protection purposes has, therefore, been developed. Biokinetic data for 13 11C-radiopharmaceuticals used clinically for imaging different brain receptors indicate that, despite differences in chemical structure, their uptake and retention in the human brain and other tissues are broadly similar. The proposed model assumes instantaneous deposition of 5% of the injected radioactivity in the brain, with the remaining radioactivity being rapidly and uniformly distributed throughout all other tissues. Elimination from all tissues is assumed to occur with a half-time of 2 h. It is further assumed that 75% of the injected 11C is excreted in the urine, and 25% via the gall bladder, with a half-time of 2 h. This model yields an effective dose of 4.5 x 10(-3) mSv MBq(-1), with doses of 3.2 x 10(-2), 1.7 x 10(-2), 8.7 x 10(-3), 5.2 x 10(-3), and 3.8 x 10(-3) mGy MBq(-1) to the urinary bladder, gall bladder, kidneys, brain and ovaries, respectively. These doses are well within the range of those reported using compound-specific models for the radiopharmaceutals studied.

Biokinetics of iodide in man: refinement of current ICRP dosimetry models.

A compartmental model describing the distribution and retention of radioactive iodide in thyroid and other organs is presented. The model is developed from published ICRP models. It is designed primarily for radiation dosimetry of iodine radionuclides used in nuclear medicine, but may also be useful for occupational radiation protection. In the proposed model, the distribution of iodide to the thyroid is assumed to be more rapid than in earlier models. Uptakes in stomach wall and salivary glands are considered, and the absorbed doses to these organs calculated. The partitioning of iodide between stomach wall and content is also discussed. Recirculation of organic iodine is also taken into account. Age-dependent half-times for iodide in the thyroid, as well as for organically-bound iodine are presented. The proposed model is applicable for dose estimations with different uptakes in the thyroid as well as for the situation when the thyroid is blocked, completely or incompletely.

No radiation protection reasons for restrictions on 14C urea breath tests in children.

Traditional (14)C urea breath tests are normally not used for younger children because the radiation exposure is unknown. High sensitivity accelerator mass spectrometry and an ultra-low amount (440 Bq) of (14)C urea were therefore used both to diagnose Helicobacter pylori (HP) infection in seven children, aged 3-6 years, and to make radiation dose estimates. The activity used was 125 times lower than the amount normally used for older children and 250 times lower than that used for adults. Results were compared with previously reported biokinetic and dosimetric data for adults and older children aged 7-14 years. (14)C activity concentrations in urine and exhaled air per unit administered activity for younger children (3-6 years) correspond well with those for older children (7-14 years). For a child aged 3-6 years who is HP negative, the urinary bladder wall receives the highest absorbed dose, 0.3 mGy MBq(-1). The effective dose is 0.1 mSv MBq(-1) for the 3-year-old child and 0.07 mSv MBq(-1) for the 6-year-old child. For two children, the 10 min and 20 min post-(14)C administration samples of exhaled air showed a significantly higher amount of (14)C activity than for the rest of the children, that is 6% and 19% of administered activity exhaled per hour compared with 0.3-0.9% (mean 0.5%) of administered activity exhaled per hour indicating that these two children that is were HP positive. For a 3-year-old HP positive child, absorbed dose to the urinary bladder wall was 0.3 mGy MBq(-1) and effective dose per unit of administered activity was 0.4 mSv MBq(-1). Using 55 kBq, which is a normal amount for older children when liquid scintillation counters are used for measurement, the effective dose will be approximately 6 micro Sv to a 3-year-old HP negative child and 20 microSv to a HP positive child. Thus there is no reason for restrictions on performing a normal (14)C urea breath test, even on young children.

Biokinetics and radiation doses for carbon-14 urea in adults and children undergoing the Helicobacter pylori breath test.

The long-term biokinetics and dosimetry of carbon-14 were studied in nine adults and eight children undergoing carbon-14 urea breath test for Helicobacter pylori (HP) infection. The elimination of 14C via exhaled air and urine was measured with the liquid scintillation counting technique and with accelerator mass spectrometry. After the subjects had been given 110 kBq 14C-urea (children: 55 kBq) orally, samples of exhaled air were taken up to 180 days after administration and samples of urine were collected up to 40 days. Sixteen of the subjects were found to be HP-negative. In these subjects a total of 91.1%+/-3.9% (mean of adults and children +/- standard error of the mean) of the administered 14C activity was recovered. The majority of the administered activity, 88.3%+/-6.2% in adults and 87.7%+/-5.0% in children, was excreted via the urine within 72 h after administration. A smaller fraction was exhaled. In adults 4.6%+/-0.6% of the activity was exhaled within 20 days and in children 2.6%+/-0.3%. Uncertainties in the biokinetic results are mainly due to assumptions concerning endogenous CO2 production and urinary excretion rate and are estimated to be less than 30%. The absorbed dose to various organs and the effective dose were calculated using the ICRP model for urea and CO2. The urinary bladder received the highest absorbed dose: in adults, 0.15+/-0.01 mGy/MBq and in children of various ages (7-14 years), 0.14-0.36 mGy/MBq. The findings indicate that an investigation with 14C-urea gives an effective dose to adults of 2.1+/-0.1 microSv (for 110 kBq) and to children of 0.9-2.5 microSv (for 55 kBq). From a radiation protection point of view, there is thus no reason for restrictions on even repeated screening investigations with 14C-urea in whole families, including children.

Application of accelerator mass spectrometry (AMS) for high-sensitivity measurements of 14CO2 in long-term studies of fat metabolism.

Long-term measurements of 14C in CO2 expired after ingestion of 14C-labelled triolein were performed using accelerator mass spectrometry (AMS). About 30% of a given amount of 14C-labelled triolein was catabolized rapidly, while the remaining 70% had a very slow turnover. The study shows the potential of the AMS technique for the study of the long-term biokinetics of 14C-labelled pharmaceuticals. The AMS technique allows the administered activity to be reduced by several orders of magnitude without compromising the study. It may also allow studies of rare drug metabolites.

Effective dose from radiopharmaceuticals.

The effective dose, as defined by the International Commission on Radiological Protection (ICRP 1991), provides a possibility of expressing the radiation risk to patients undergoing different radiodiagnostic procedures by means of a single figure. This has been obtained by introducing organ or tissue weighting factors reflecting the radiation sensitivity of the organs. Such weighting factors were first published by the ICRP in publication 26 (1977), and have now been revised in publication 60 (1991). The effective dose for almost all radiopharmaceuticals in clinical use has been recalculated using the new weighting factors from ICRP 60 (1991) and compared with results from former calculations. A slight decrease in the numerical value for the effective dose has been observed, on average 11%. However, this does not correspond to a decrease in the estimated risk from the irradiation, since this has been re-evaluated and found to be higher than earlier believed (NAS 1990; ICRP 1991).