A revised compartmental model for biokinetics and dosimetry of 2-[18F]FDG.

BACKGROUND: The aim was to review available biokinetic data, collect own experimental data, and propose an updated compartmental model for 2-[18F]FDG in the frame of the revision of the ICRP report on dose coefficients for radiopharmaceuticals used in diagnostic nuclear medicine. METHODS: The compartmental model was developed based on published biokinetic data for 2-[18F]FDG. Additional data on urinary excretion in 23 patients (11 males, 12 females) undergoing whole-body PET/CT examinations were obtained within this study. The unknown biokinetic model parameters were derived using the software SAAM II and verified with a modified version of IDAC-Iodide. Dose coefficients for reference adults were calculated with the programme IDAC-Dose 2.1. A dynamic bladder model was employed for urinary bladder dosimetry. RESULTS: The proposed model consists of following compartments: blood, heart wall, brain, liver, lungs, pancreas, spleen, kidneys, urinary bladder content and a generic pool compartment "Other". The latter was introduced to account for 2-[18F]FDG in body organ and tissues besides the explicitly modelled ones. The model predictions showed a good agreement with experimental data. Urinary bladder wall received the highest absorbed dose coefficient of 7.5E-02 mGy/MBq under the assumption of initial urine volume of 100 ml, first voiding at 45 min p.i. and 3.75 h voiding intervals thereafter. The effective dose coefficient calculated according to the current dosimetry framework of ICRP amounted to 1.7E-02 mSv/MBq, compared to 1.9E-02 mSv/MBq in ICRP Publication 128. CONCLUSION: A compartmental model for 2-[18F]FDG was proposed and will be used to replace the descriptive biokinetic model of ICRP Publication 128. The revised model and the provided dose coefficients are expected to improve reference dosimetry for patients administered with 2-[18F]FDG.

Extremity exposure of nuclear medicine workers: results from an EANM and EURADOS survey.

BACKGROUND: Extremity exposure during the handling of unsealed radioactive sources is a matter of concern for nuclear medicine workers. Next to 99mTc and 18F, other radiopharmaceuticals have seen an increase in their use over the last decade. However, limited information on their impact on extremity dose is available. This study aimed to gain insight into the status of extremity exposure and dose monitoring in Europe. METHODS: A survey was conducted at the end of 2020 among the European Association of Nuclear Medicine community. It contained 24 questions considering department characteristics, worker tasks, dosimeter use, typical worker extremity dose, department workload for selected radionuclides (99mTc, 18F, 68Ga, 177Lu, 90Y) and protective measures. RESULTS: A total of 106 replies were received, 92% of which were from Europe. About half of the respondents were from academic hospitals. Ninety-nine departments implement extremity dose monitoring for a total of 1335 workers. Most workers (95%) wear a ring dosimeter, generally on the non-dominant hand, and 44% on the index finger. Monthly doses were generally low (median values at different ring position: 0.4-1.8 mSv), although higher doses were reported (20.8-38.8 mSv). About 1/3 of workers performed the full task range (preparation, dispensing, and administration). Administration is associated with significantly lower extremity doses. Interestingly, no correlation between department workload and collective dose was found. The adoption of vial and syringe shielding, as well as distance tools, was common. The workers dispensing 99mTc without syringe shielding or PET nuclides without automated system received a significantly higher dose. Handling 68Ga, 177Lu and 90Y did not appear to have an impact on the reported doses. CONCLUSIONS: Protective measures play a significant role in lowering extremity doses, while department workload and more recently introduced radionuclides seem not to be major dose determinants.

X-RAY AND MOLECULAR IMAGING DURING PREGNANCY AND BREASTFEEDING-WHEN SHOULD WE BE WORRIED?

Some of the ethically most sensitive issues in radiation protection arise at imaging of pregnant-and potentially pregnant-patients and of newborn. This article reviews the current literature and recommendations on imaging during pregnancy and breastfeeding. Risks related to alternative non-ionizing radiation methods are also considered. With few exceptions, exposure of the fetus through radiography, computed tomography (CT) and nuclear medicine imaging can be limited to safe levels, although studies such as abdominal-pelvic CT cannot avoid significant exposure to fetuses. Eight to 10 weeks post-conception, the fetus has a thyroid which starts to concentrate iodide having crossed the placenta barrier resulting in unacceptably high doses to the fetal thyroid after administration of 131I- and even 123I-iodide and other radiopharmaceuticals with a high content of free radioiodine. Many radiopharmaceuticals are excreted through breast milk. Breastfeeding interruption recommendations should be followed to keep the effective dose to the infant below 1 mSv.

Comparison of conventional and Si-photomultiplier-based PET systems for image quality and diagnostic performance.

BACKGROUND: A new generation of positron emission tomography with computed tomography (PET-CT) was recently introduced using silicon (Si) photomultiplier (PM)-based technology. Our aim was to compare the image quality and diagnostic performance of a SiPM-based PET-CT (Discovery MI; GE Healthcare, Milwaukee, WI, USA) with a time-of-flight PET-CT scanner with a conventional PM detector (Gemini TF; Philips Healthcare, Cleveland, OH, USA), including reconstruction algorithms per vendor's recommendations. METHODS: Imaging of the National Electrical Manufacturers Association IEC body phantom and 16 patients was carried out using 1.5 min/bed for the Discovery MI PET-CT and 2 min/bed for the Gemini TF PET-CT. Images were analysed for recovery coefficients for the phantom, signal-to-noise ratio in the liver, standardized uptake values (SUV) in lesions, number of lesions and metabolic TNM classifications in patients. RESULTS: In phantom, the correct (> 90%) activity level was measured for spheres ≥17 mm for Discovery MI, whereas the Gemini TF reached a correct measured activity level for the 37-mm sphere. In patient studies, metabolic TNM classification was worse using images obtained from the Discovery MI compared those obtained from the Gemini TF in 4 of 15 patients. A trend toward more malignant, inflammatory and unclear lesions was found using images acquired with the Discovery MI compared with the Gemini TF, but this was not statistically significant. Lesion-to-blood-pool SUV ratios were significantly higher in images from the Discovery MI compared with the Gemini TF for lesions smaller than 1 cm (p < 0.001), but this was not the case for larger lesions (p = 0.053). The signal-to-noise ratio in the liver was similar between platforms (p = 0.52). Also, shorter acquisition times were possible using the Discovery MI, with preserved signal-to-noise ratio in the liver. CONCLUSIONS: Image quality was better with Discovery MI compared to conventional Gemini TF. Although no gold standard was available, the results indicate that the new PET-CT generation will provide potentially better diagnostic performance.

A biokinetic and dosimetric model for ionic indium in humans.

This paper reviews biokinetic data for ionic indium, and proposes a biokinetic model for systemic indium in adult humans. The development of parameter values focuses on human data and indium in the form of ionic indium(III), as indium chloride and indium arsenide. The model presented for systemic indium is defined by five different pools: plasma, bone marrow, liver, kidneys and other soft tissues. The model is based on two subsystems: one corresponding to indium bound to transferrin and one where indium is transported back to the plasma, binds to red blood cell transferrin and is then excreted through the kidneys to the urinary bladder. Absorbed doses to several organs and the effective dose are calculated for 111In- and 113mIn-ions. The proposed biokinetic model is compared with previously published biokinetic indium models published by the ICRP. The absorbed doses are calculated using the ICRP/ICRU adult reference phantoms and the effective dose is estimated according to ICRP Publication 103. The effective doses for 111In and 113mIn are 0.25 mSv MBq-1 and 0.013 mSv MBq-1 respectively. The updated biokinetic and dosimetric models presented in this paper take into account human data and new animal data, which represent more detailed and presumably more accurate dosimetric data than that underlying previous models for indium.

ORGAN DOSES AND EFFECTIVE DOSE FOR FIVE PET RADIOPHARMACEUTICALS.

Diagnostic investigations with positron-emitting radiopharmaceuticals are dominated by (18)F-fluorodeoxyglucose ((18)F-FDG), but other radiopharmaceuticals are also commercially available or under development. Five of them, which are all clinically important, are (18)F-fluoride, (18)F-fluoroethyltyrosine ((18)F-FET), (18)F-deoxyfluorothymidine ((18)F-FLT), (18)F-fluorocholine ((18)F-choline) and (11)C-raclopride. To estimate the potential risk of stochastic effects (mainly lethal cancer) to a population, organ doses and effective dose values were updated for all five radiopharmaceuticals. Dose calculations were performed using the computer program IDAC2.0, which bases its calculations on the ICRP/ICRU adult reference voxel phantoms and the tissue weighting factors from ICRP publication 103. The biokinetic models were taken from ICRP publication 128. For organ doses, there are substantial changes. The only significant change in effective dose compared with previous estimations was a 46 % reduction for (18)F-fluoride. The estimated effective dose in mSv MBq(-1) was 1.5E-02 for (18)F-FET, 1.5E-02 for (18)F-FLT, 2.0E-02 for (18)F-choline, 9.0E-03 for (18)F-fluoride and 4.4E-03 for (11)C-raclopride.

Excretion of radionuclides in human breast milk after nuclear medicine examinations. Biokinetic and dosimetric data and recommendations on breastfeeding interruption.

PURPOSE: To review early recommendations and propose guidelines for breastfeeding interruption after administration of radiopharmaceuticals, based on additional biokinetic and dosimetric data. METHODS: Activity concentrations in breast milk from 53 breastfeeding patients were determined. The milk was collected at various times after administration of 16 different radiopharmaceuticals. The fraction of the activity administered to the mother excreted in the breast milk, the absorbed doses to various organs and tissues and the effective dose to the infant were estimated. RESULTS: The fraction of the administered activity excreted per millilitre of milk varied widely from 10(-10) to 10(-3) MBq/MBq administered. For (99m)Tc-labelled radiopharmaceuticals, the total fraction of the administered activity excreted in the milk varied from 0.0057 % for (99m)Tc-labelled red blood cells (RBC) to 19 % for (99m)Tc-pertechnetate. The effective dose to an infant per unit activity administered to the mother ranged from 6.7 × 10(-6) mSv/MBq for (99m)Tc-labelled RBC to 3.6 × 10(-2) mSv/MBq for (99m)Tc-pertechnetate. For the other radiopharmaceuticals, the total fraction of administered activity excreted in the milk varied from 0.018 % ((51)Cr-EDTA) to 48 % ((131)I-NaI). The effective dose ranged from 5.6 × 10(-5) mSvinfant/MBqmother ((51)Cr-EDTA) to 106 mSvinfant/MBqmother ((131)I-NaI). CONCLUSIONS: Based on an effective dose limit of 1 mSv to the infant and a typical administered activity, we recommend cessation of breastfeeding for (131)I-NaI and interruption of feeding for 12 h for (125)I-iodohippurate, (131)I-iodohippurate, (99m)Tc-pertechnetate and (99m)Tc-MAA. During this 12-h period all breast milk should be expressed at least three times and discarded. For the other radiopharmaceuticals included in this study, no interruption of breastfeeding is necessary.

Improved estimates of the radiation absorbed dose to the urinary bladder wall.

Specific absorbed fractions (SAFs) have been calculated as a function of the content in the urinary bladder in order to allow more realistic calculations of the absorbed dose to the bladder wall. The SAFs were calculated using the urinary bladder anatomy from the ICRP male and female adult reference computational phantoms. The urinary bladder and its content were approximated by a sphere with a wall of constant mass, where the thickness of the wall depended on the amount of urine in the bladder. SAFs were calculated for males and females with 17 different urinary bladder volumes from 10 to 800 mL, using the Monte Carlo computer program MCNP5, at 25 energies of mono-energetic photons and electrons ranging from 10 KeV to 10 MeV. The decay was assumed to be homogeneously distributed in the urinary bladder content and the urinary bladder wall, and the mean absorbed dose to the urinary bladder wall was calculated. The Monte Carlo simulations were validated against measurements made with thermoluminescent dosimeters. The SAFs obtained for a urine volume of 200 mL were compared to the values calculated for the urinary bladder wall using the adult reference computational phantoms. The mean absorbed dose to the urinary wall from (18)F-FDG was found to be 77 µGy/MBq formales and 86 µGy/MBq for females, while for (99m)Tc-DTPA the mean absorbed doses were 80 µGy/MBq for males and 86 µGy/MBq for females. Compared to calculations using a constant value of the SAF from the adult reference computational phantoms, the mean absorbed doses to the bladder wall were 60% higher for (18)F-FDG and 30% higher for (99m)Tc-DTPA using the new SAFs.

Use of wall-less ¹8F-doped gelatin phantoms for improved volume delineation and quantification in PET/CT.

Positron emission tomography (PET) with (18)F-FDG is a valuable tool for staging, planning treatment, and evaluating the treatment response for many different types of tumours. The correct volume estimation is of utmost importance in these situations. To date, the most common types of phantoms used in volume quantification in PET utilize fillable, hollow spheres placed in a circular or elliptical cylinder made of polymethyl methacrylate. However, the presence of a non-radioactive sphere wall between the hotspot and the background activity in images of this type of phantom could cause inaccuracies. To investigate the influence of the non-active walls, we developed a phantom without non-active sphere walls for volume delineation and quantification in PET. Three sizes of gelatin hotspots were moulded and placed in a Jaszczak phantom together with hollow plastic spheres of the same sizes containing the same activity concentration. (18)F PET measurements were made with zero background activity and with tumour-to-background ratios of 12.5, 10, 7.5, and 5. The background-corrected volume reproducing threshold, Tvol, was calculated for both the gelatin and the plastic spheres. It was experimentally verified that the apparent background dependence of Tvol, i.e., a decreasing Tvol with increasing background fraction, was not present for wall-less spheres; the opposite results were seen in plastic, hollow spheres in commercially-available phantoms. For the types of phantoms commonly used in activity quantification, the estimation of Tvol using fillable, hollow, plastic spheres with non-active walls would lead to an overestimate of the tumour volume, especially for small volumes in a high activity background.

Effective dose to adult patients from 338 radiopharmaceuticals estimated using ICRP biokinetic data, ICRP/ICRU computational reference phantoms and ICRP 2007 tissue weighting factors.

BACKGROUND: Effective dose represents the potential risk to a population of stochastic effects of ionizing radiation (mainly lethal cancer). In recent years, there have been a number of revisions and updates influencing the way to estimate the effective dose. The aim of this work was to recalculate the effective dose values for the 338 different radiopharmaceuticals previously published by the International Commission on Radiological Protection (ICRP). METHOD: The new estimations are based on information on the cumulated activities per unit administered activity in various organs and tissues and for the various radiopharmaceuticals obtained from the ICRP publications 53, 80 and 106. The effective dose for adults was calculated using the new ICRP/International Commission on Radiation Units (ICRU) reference voxel phantoms and decay data from the ICRP publication 107. The ICRP human alimentary tract model has also been applied at the recalculations. The effective dose was calculated using the new tissue weighting factors from ICRP publications 103 and the prior factors from ICRP publication 60. The results of the new calculations were compared with the effective dose values published by the ICRP, which were generated with the Medical Internal Radiation Dose (MIRD) adult phantom and the tissue weighting factors from ICRP publication 60. RESULTS: For 79% of the radiopharmaceuticals, the new calculations gave a lower effective dose per unit administered activity than earlier estimated. As a mean for all radiopharmaceuticals, the effective dose was 25% lower. The use of the new adult computational voxel phantoms has a larger impact on the change of effective doses than the change to new tissue weighting factors. CONCLUSION: The use of the new computational voxel phantoms and the new weighting factors has generated new effective dose estimations. These are supposed to result in more realistic estimations of the radiation risk to a population undergoing nuclear medicine investigations than hitherto available values.

Determination of the biodistribution and dosimetry of ¹²³I-FP-CIT in male patients with suspected Parkinsonism or Lewy body dementia using planar and combined planar and SPECT/CT imaging.

In this study, (123)I-FP-CIT biodistribution and dosimetry was determined in 10 adult male patients using planar gamma camera imaging alone or in combination with single photon emission computed tomography /X-ray computed tomography (SPECT/CT) imaging. Dosimetric assessment using planar plus SPECT/CT imaging resulted in significantly different estimates of organ-absorbed doses compared to estimates based on planar imaging alone. We conclude that the use of complementary SPECT/CT measurements in biodistribution studies is valuable for determining the organ doses more accurately.

Evaluation of image reconstruction methods for (123)I-MIBG-SPECT: a rank-order study.

BACKGROUND: There is an opportunity to improve the image quality and lesion detectability in single photon emission computed tomography (SPECT) by choosing an appropriate reconstruction method and optimal parameters for the reconstruction. PURPOSE: To optimize the use of the Flash 3D reconstruction algorithm in terms of equivalent iteration (EI) number (number of subsets times the number of iterations) and to compare with two recently developed reconstruction algorithms ReSPECT and orthogonal polynomial expansion on disc (OPED) for application on (123)I-metaiodobenzylguanidine (MIBG)-SPECT. MATERIAL AND METHODS: Eleven adult patients underwent SPECT 4 h and 14 patients 24 h after injection of approximately 200 MBq (123)I-MIBG using a Siemens Symbia T6 SPECT/CT. Images were reconstructed from raw data using the Flash 3D algorithm at eight different EI numbers. The images were ranked by three experienced nuclear medicine physicians according to their overall impression of the image quality. The obtained optimal images were then compared in one further visual comparison with images reconstructed using the ReSPECT and OPED algorithms. RESULTS: The optimal EI number for Flash 3D was determined to be 32 for acquisition 4 h and 24 h after injection. The average rank order (best first) for the different reconstructions for acquisition after 4 h was: Flash 3D(32) > ReSPECT > Flash 3D(64) > OPED, and after 24 h: Flash 3D(16) > ReSPECT > Flash 3D(32) > OPED. A fair level of inter-observer agreement concerning optimal EI number and reconstruction algorithm was obtained, which may be explained by the different individual preferences of what is appropriate image quality. CONCLUSION: Using Siemens Symbia T6 SPECT/CT and specified acquisition parameters, Flash 3D(32) (4 h) and Flash 3D(16) (24 h), followed by ReSPECT, were assessed to be the preferable reconstruction algorithms in visual assessment of (123)I-MIBG images.

A compartmental model for biokinetics and dosimetry of 18F-choline in prostate cancer patients.

UNLABELLED: PET with (18)F-choline ((18)F-FCH) is used in the diagnosis of prostate cancer and its recurrences. In this work, biodistribution data from a recent study conducted at Skåne University Hospital Malmö were used for the development of a biokinetic and dosimetric model. METHODS: The biodistribution of (18)F-FCH was followed for 10 patients using PET up to 4 h after administration. Activity concentrations in blood and urine samples were also determined. A compartmental model structure was developed, and values of the model parameters were obtained for each single patient and for a reference patient using a population kinetic approach. Radiation doses to the organs were determined using computational (voxel) phantoms for the determination of the S factors. RESULTS: The model structure consists of a central exchange compartment (blood), 2 compartments each for the liver and kidneys, 1 for spleen, 1 for urinary bladder, and 1 generic compartment accounting for the remaining material. The model can successfully describe the individual patients' data. The parameters showing the greatest interindividual variations are the blood volume (the clearance process is rapid, and early blood data are not available for several patients) and the transfer out from liver (the physical half-life of (18)F is too short to follow this long-term process with the necessary accuracy). The organs receiving the highest doses are the kidneys (reference patient, 0.079 mGy/MBq; individual values, 0.033-0.105 mGy/MBq) and the liver (reference patient, 0.062 mGy/MBq; individual values, 0.036-0.082 mGy/MBq). The dose to the urinary bladder wall of the reference patient varies between 0.017 and 0.030 mGy/MBq, depending on the assumptions on bladder voiding. CONCLUSION: The model gives a satisfactory description of the biodistribution of (18)F-FCH and realistic estimates of the radiation dose received by the patients.

Low-level occupational 14C contamination--results from a pilot study.

This paper presents a pilot study in which specific activities of 14C in hair and urine from 11 radiation workers handling 14C-containing substances have been measured using accelerator mass spectrometry. Varying degrees of contamination were revealed: up to 63% excess in hair and 400% excess in urine. Although the 14C excess reported in this study would result in low effective doses, it would be of interest to monitor the situation at other workplaces with potentially higher risks of contamination. Simultaneous measurements of 14C in hair and urine with additional random measurements of 14C in faeces and exhaled air could provide a means of improving dose estimates for workers handling different types of 14C-containing substances.

Long-term biokinetics and radiation exposure of patients undergoing 14C-glycocholic acid and 14C-xylose breath tests.

The (14)C-glycocholic acid and (14)C-xylose breath tests are clinically used for the diagnosis of intestinal diseases, such as bacterial overgrowth in the small intestine. The two tests have in earlier studies been thoroughly evaluated regarding their clinical value, but due to the long physical half-life of (14)C and the limited biokinetic and dosimetric data, which are available for humans, several hospitals have been restrictive in their use. The aim of this study was to investigate the long-term biokinetics and dosimetry of the two (14)C compounds in patients and volunteers, using the highly sensitive accelerator mass spectrometry (AMS) technique. Eighteen (18) subjects were included, 9 for each compound. The (14)C content in samples from exhaled air, urine, and, for some subjects, also feces were analyzed with both liquid scintillation counting (LSC) and AMS. The results from the glycocholic acid study showed that, up to 1 year after the administration, 67%+/-6% (mean+/-standard deviation) of the administered activity was recovered in exhaled air, 2.4%+/-0.4% was found in urine, and 7.6% (1 subject) in feces. In the xylose study, the major part was found in the urine (66%+/-2%). A significant part was exhaled (28%+/-5%), and the result from an initial 72-hour stool collection from 2 of the subjects showed that the excretion by feces was insignificant. The absorbed dose to various organs and tissues and the effective dose were calculated by using biokinetic models, based on a combination of experimental data from the present study and from earlier reports. In the glycocholic acid study, the highest absorbed dose was received by the colon (1.2 mGy/MBq). In the xylose study, the adipose tissue received 0.8 mGy/MBq. The effective dose was estimated to 0.5 (glycocholic acid) and 0.07 mSv/MBq (xylose). Thus, from a radiation protection point of view, we see no need for restrictions in using the two (14)C-labeled radiopharmaceuticals on adults with the activities normally administered (0.07-0.4 MBq).

Biokinetics and radiation dosimetry for patients undergoing a glycerol tri[1-14C]oleate fat malabsorption breath test.

The glycerol tri[1-14C]olein test for fat malabsorption was carried out in two male volunteers and measurements of the loss of 14C in expired air, urine and faeces and the retention of 14C in biopsy samples of abdominal fat were made using accelerator mass spectrometry. Exhalation accounted for 73% and 55% of the administered activity and could be described by three-component exponential functions with halftimes of about 1h, 2 days and 150 days, respectively. Urinary excretion accounted for 24% of the administered activity, almost all during the first 24h after administration; about 2% was excreted in the faeces in 48h. The halftime of retention of 14C in fat ranged from 137 to 620 days. Absorbed dose calculations indicate that for a normal adult the largest dose, 1.5-7.0mGy/MBq is received by the adipose tissue, and that the effective dose is 0.3-0.5mSv/MBq. It is concluded that no restrictions need to be placed on radiation safety grounds on the administration of 0.05-0.1MBq 14C-triolein for the triolein breath test.