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.     

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.     

Human biodistribution and dosimetry of [123I]FP-CIT: a potent radioligand for imaging of dopamine transporters

This study reports on the biodistribution and radiation dosimetry of iodine-123-labelled N-ω-(flu- oropropyl)-2β-carbomethoxy-3β-(4-iodophenyl)tropane ([¹²³I]FP-CIT), a promising radioligand for the imaging of dopamine transporters. In 12 healthy volunteers, conjugate whole-body scans were performed up to 48 h following intravenous injection of approximately 100 MBq [¹²³I]FP-CIT. Attenuation correction was performed using a transmission whole-body scan obtained prior to injection of the radioligand, employing a ¹²³I flood source. Blood samples were taken and urine was freely collected up to 48 h after injection of the radiotracer. For each subject, the percentage of injected activity measured in regions of interest over brain, striatum, lungs and liver were fitted to a multicompartmental model to give time-activity curves. The cumulative urine activity curve was used to model the urinary excretion rate and, indirectly, to predict faecal excretion. Using the MIRD method, nine source organs were considered in estimating absorbed radiation doses for organs of the body. The images showed rapid lung uptake and hepatobiliary excretion. Diffuse uptake and retention of activity was seen in the brain, especially in the striatum. At 48 h following the injection of [¹²³I]FP-CIT, mean measured urine excretion was 60%±9% (SD), and mean predicted excretion in faeces was 14%±1%. In general, the striatum received the highest absorbed dose (average 0.23 mGy/MBq), followed by the urinary bladder wall (average 0.054 mGy/MBq) and lungs (average 0.043 mGy/MBq). The average effective dose equivalent of [¹²³I]FP-CIT was estimated to be 0.024 mSv/MBq. The amount of [¹²³I]FP-CIT required for adequate dopamine transporter imaging results in an acceptable effective dose equivalent to the patient. Received 14 July and in revised form 26 September 1997     

Biodistribution and dosimetry of iodine-123-labelled Z -MIVE: an oestrogen receptor radioligand for breast cancer imaging

This study reports on the distribution and radiation dosimetry of iodine-123-labelled cis-11β-methoxy-17α-iodovinyloestradiol (Z-[¹²³I]MIVE), a promising radioligand for imaging of oestrogen receptors (ERs) in human breast cancer. Whole-body scans were performed up to 24 h after intravenous injection of 138–193 MBq Z-[¹²³I]MIVE in five healthy female volunteers, four with and one without thyroid blockade. Blood samples were taken at various times up to 24 h after injection. Urine was collected up to 24 h after injection in order to calculate renal clearance and to aid in the interpretation of whole-body clearance, including faecal excretion. Time-activity curves were generated for the thyroid, heart, brain, breasts and liver, by fitting the organ-specific geometric mean counts, obtained from regions of interest, to a multicompartmental model. The MIRD formulation, using 11 source organs, was applied to calculate the absorbed radiation doses for various organs upon administration of Z-[¹²³I]MIVE. The images showed rapid hepatobiliary excretion which resulted in good imaging conditions for the thoracic region. Imaging of the abdominal region was impeded due to extensive bowel activity. Diffuse uptake and retention of activity was seen in breast tissue, the breast-to-non-specific uptake ratio increasing over time. Z-[¹²³I]MIVE was cleared by both the kidneys and the gastrointestinal tract. At 50 h p.i. the mean excretion in urine was predicted to be 58%±14% (SD) and that in faeces 31%±19%. If the thyroid was not blocked, it was the most critical organ (0.33 mGy/MBq). In general, the excretory organs received the highest absorbed doses, i.e. the lower and upper large intestinal walls (0.11 and 0.098 mGy/MBq, respectively), the urinary bladder wall (0.090 mGy/MBq), the gallbladder wall (0.087 mGy/MBq) and the small intestine (0.043 mGy/MBq). The average effective dose equivalent of Z-[¹²³I]MIVE was estimated to be 0.033 mSv/MBq. The amount of Z-[¹²³I]MIVE required for adequate breast cancer ER imaging results in an acceptable effective dose equivalent to the patient. Received 28 June and in revised form 26 September 1997     

Three-step radioimmunotherapy with yttrium-90 biotin: dosimetry and pharmacokinetics in cancer patients

. A three-step avidin-biotin approach has been applied as a pretargeting system in radioimmunotherapy (RIT) as an alternative to conventional RIT with directly labelled monoclonal antibodies (MoAbs). Although dosimetric and toxicity studies following conventional RIT have been reported, these aspects have not previously been evaluated in a three-step RIT protocol. This report presents the results of pharmacokinetic and dosimetric studies performed in 24 patients with different tumours. Special consideration was given to the dose delivered to the red marrow and to the haematological toxicity. The possible additive dose to red marrow due to the release of unbound yttrium-90 was investigated. The protocol consisted in the injection of biotinylated MoAbs (first step) followed 1 day later by the combined administration of avidin and streptavidin (second step). After 24 h, biotin radiolabelled with 1.85–2.97 GBq/m² of ⁹⁰Y was injected (third step). Two different chelating agents, DTPA and DOTA, coupled to biotin, were used in these studies. Indium-111 biotin was used as a tracer of ⁹⁰Y to follow the biodistribution during therapy. Serial blood samples and complete urine collection were obtained over 3 days. Whole-body and single-photon emission tomography images were acquired at 1, 16, 24 and 40 h after injection. The sequence of images was used to extrapolate ⁹⁰Y-biotin time-activity curves. Numerical fitting and compartmental modelling were used to calculate the residence time values (τ) for critical organs and tumour, and results were compared; the absorbed doses were estimated using the MIRDOSE3.1 software. The residence times obtained by the numerical and compartmental models showed no relevant differences (<10%); the compartmental model seemed to be more appropriate, giving a more accurate representation of the exchange between organs. The mean value for the τ in blood was 2.0±1.1 h; the mean urinary excretion in the first 24 h was 82.5%±10.8%. Without considering any contribution of free ⁹⁰Y, kidneys, liver, bladder and red marrow mean absorbed doses were 1.62±1.14, 0.27±0.23, 3.61±0.70 and 0.11±0.05 mGy/MBq, respectively; the effective dose was 0.32±0.06 mSv/MBq, while the dose to the tumour ranged from 0.62 to 15.05 mGy/MBq. The amount of free ⁹⁰Y released after the injection proved to be negligible in the case of ⁹⁰Y-DOTA-biotin, but noteworthy in the case of ⁹⁰Y-DTPA-biotin (mean value: 5.6%±2.5% of injected dose), giving an additive dose to red marrow of 0.18±0.08 mGy per MBq of injected ⁹⁰Y-DTPA-biotin. Small fractions of free ⁹⁰Y originating from incomplete radiolabelling can contribute significantly to the red marrow dose (3.26 mGy per MBq of free ⁹⁰Y) and may explain some of the high levels of haematological toxicity observed. These results indicate that pretargeted three-step RIT allows the administraton of high ⁹⁰Y activities capable of delivering a high dose to the tumour and sparing red marrow and other normal organs. Although ⁹⁰Y-biotin clears rapidly from circulation, the use of DOTA-biotin conjugate for a stable chelation of ⁹⁰Y is strongly recommended, considering that small amounts of free ⁹⁰Y contribute significantly in increasing the red marrow dose. Received 6 June and in revised form 19 September 1998     

Dosimetric analysis of chimeric monoclonal antibody cMOv18 IgG in ovarian carcinoma patients after intraperitoneal and intravenous administration

In this study the potential of intraperitoneal (i.p.) and intravenous (i.v.) administration of chimeric iodine-131-labelled MOv18 IgG for radioimmunotherapy was determined. The dosimetry associated with both routes of administration of cMOv18 IgG was studied in patients. Eight patients suspected of having ovarian carcinoma received 150 MBq ¹³¹I-cMOv18 IgG i.p. Blood and urine were collected and serial gamma camera images were acquired. Another group of four patients received 7.5 MBq ¹³¹I-cMOv18 IgG i.v. For all patients, tissue biopsies were obtained at surgery. Activity in the blood after i.p. administration was described by a bi-exponential curve with a mean uptake and elimination half-life of 6.9±3.2 h and 160±45 h, respectively. For i.v. infusion the mean half-life for the elimination phase was 103±12 h. Cumulative excretion in the urine was 17%±3% ID and 21%±7% ID in 96 h for i.p. and i.v. administration, respectively. Scintigraphic images after i.p. administration showed accumulation in ovarian cancer lesions, while all other tissues showed decreasing activity with time. Tumour uptake determined in the ovarian cancer tissue specimens ranged from 3.4% to 12.3% ID/kg for i.p. administration and from 3.6% to 5.4% ID/kg for i.v. administration. Dosimetric analysis of the data indicated that 1.7–4.3 mGy/MBq and 1.7–2.2 mGy/MBq can be guided to solid or ascites cells after i.p. and i.v. administration, respectively. Assuming that an absorbed dose to the bone marrow of 2 Gy will be dose limiting, a total activity of 4.1 GBq ¹³¹I-cMOv18 IgG can be administered safely via the i.p. route and 3.5 GBq via the i.v. route. At this maximal tolerated dose, a maximum absorbed dose to 1-g tumours in the peritoneal cavity of 18 and 8 Gy can be reached after i.p. and i.v. administration, respectively. For the i.p. route of administration, dose estimates for the tumour are even higher when the electron dose of the peritoneal activity is also taken into account: total doses to the tumour of 30 Gy and 22 Gy will be absorbed at the tumour surface and at 0.2 mm depth, respectively. In conclusion, therapeutic tumour doses can be achieved with ¹³¹I-cMOv18 IgG in patients with intraperitoneal ovarian cancer lesions with no normal organ toxicity. The i.p. route of administration seems to be preferable to i.v. administration. Received 10 July and in revised form 17 August 1998     

Measurement of the internal dose to families of outpatients treated with <Superscript>131</Superscript>I for hyperthyroidism

Objective  The aim of this study was to measure the internal dose received by family members from ingestion of radioactive contamination after outpatient therapy. Materials and methods  Advice was given to minimise transfer of radioiodine. Home visits were made approximately 2, 7 and 21 days after treatment to measure radioactivity in the thyroids of family members. A decay correction was applied to radioactivity detected assuming ingestion had occurred at the earlier contact time, either the day of treatment or the previous home visit. An effective half-life of 6 or 7 days was used depending on age. Thyroid activity was summed if activity was found at more than one visit in excess of the amount attributable to radioactive decay. Effective dose (ED) was calculated using ICRP72. Results and discussion  Fifty-three adults and 92 children, median age 12 (range 4–17) years participated. Median administered activity was 576 (range 329–690) MBq ¹³¹I. Thyroid activity ranged from 0 to 5.4 kBq in the adults with activity detected in 17. Maximum adult ED was 0.4 mSv. Thyroid activity ranged from 0 to 11.8 kBq in the children with activity detected in 26. The two highest values of 5.0 and 11.8 kBq occurred in children aged 5 and 14 years from different families. Eighty-five children had no activity or <1 kBq detected. ED was <0.2 mSv in 86 out of 92 children (93%). Previous published data showed 93% of children received an ED ≤0.8 mSv from external irradiation. Conclusion  With advice, families of outpatients receiving radioiodine should be able to comply with statutory dose limits and constraints.     

Dosimetry of iodine-123 iomazenil in humans

The distribution of the central benzodiazepine receptor specific ligand iodine-123 iomazenil was investigated in seven human adults from whole-body scans, blood samples and urine collected up to 24 h after injection. Using 12 source organs, the MIRD method was applied to calculate the absorbed radiation dose of the radioligand in various organs. The urinary bladder wall (0.15 mGy/MBq), lower large intestinal wall (0.071 mGy/MBq) testes (0.044 mGy/MBq) and upper large intestined wall (0.038 mGy/MBq) received the highest absorbed doses. The average effective dose equivalent of ¹²³I-IBZM for adults was estimated to be 0.033 mSv/MBq.     

Human radiation dosimetry of [11C]MeAIB, a new tracer for imaging of system A amino acid transport

Purpose [N-methyl-¹¹C]α-methylaminoisobutyric acid ([¹¹C]MeAIB) is a promising positron emission tomography (PET) tracer for imaging hormonally regulated system A amino acid transport. Uptake of [¹¹C]MeAIB is totally specific for amino acid transport since [¹¹C]MeAIB is metabolically stable both extra- and intracellularly. The aim of this study was to measure cumulated radioactivity in different organs and estimate the absorbed radiation doses to humans with the Medical Internal Radiation Dosimetry (MIRD) method.Methods Radiation absorbed doses were calculated from PET images for 25 volunteers. Dynamic acquisition data were obtained for the thoracic, abdominal, femoral and head and neck regions. The median dose of intravenously injected [¹¹C]MeAIB was 422±35 MBq, with a range of 295–493 MBq. After PET imaging the radioactivity in voided urine was measured. Experimental human data were used for residence time estimates. Radiation doses were calculated with commonly used software.Results The effective dose for a 70-kg adult was 0.004 mSv/MBq, corresponding to a 1.72 mSv effective dose from the PET study with injection of 430 MBq [¹¹C]MeAIB. The highest absorbed doses were in the pancreas (0.018 mGy/MBq), kidneys (0.017 mGy/MBq), intestine (0.014 mGy/MBq), liver (0.008 mGy/MBq) and stomach (0.005 mGy/MBq). Only 0.57% of injected activity was excreted to urine within 1 h after injection.Conclusion Biodistribution of [¹¹C]MeAIB in the abdominal region reflected the high activity of the transportation of amino acids via system A and these organs also had the highest radiation doses. An effective dose of 0.004 mSv/MBq is fully justified when [¹¹C]MeAIB PET is performed to study system A activity in vivo.     

Targeting murine heart and brain: visualisation conditions for multi-pinhole SPECT with <Superscript>99m</Superscript>Tc- and <Superscript>123</Superscript>I-labelled probes

Purpose  The study serves to optimise conditions for multi-pinhole SPECT small animal imaging of ¹²³I- and ^99mTc-labelled radiopharmaceuticals with different distributions in murine heart and brain and to investigate detection and dose range thresholds for verification of differences in tracer uptake. Methods  A Triad 88/Trionix system with three 6-pinhole collimators was used for investigation of dose requirements for imaging of the dopamine D₂ receptor ligand [¹²³I]IBZM and the cerebral perfusion tracer [^99mTc]HMPAO (1.2–0.4 MBq/g body weight) in healthy mice. The fatty acid [¹²³I]IPPA (0.94 ± 0.05 MBq/g body weight) and the perfusion tracer [^99mTc]sestamibi (3.8 ± 0.45 MBq/g body weight) were applied to cardiomyopathic mice overexpressing the prostaglandin EP₃ receptor. Results  In vivo imaging and in vitro data revealed 45 kBq total cerebral uptake and 201 kBq cardiac uptake as thresholds for visualisation of striatal [¹²³I]IBZM and of cardiac [^99mTc]sestamibi using 100 and 150 s acquisition time, respectively. Alterations of maximal cerebral uptake of [¹²³I]IBZM by >20% (116 kBq) were verified with the prerequisite of 50% striatal of total uptake. The labelling with [^99mTc]sestamibi revealed a 30% lower uptake in cardiomyopathic hearts compared to wild types. [¹²³I]IPPA uptake could be visualised at activity doses of 0.8 MBq/g body weight. Conclusion  Multi-pinhole SPECT enables detection of alterations of the cerebral uptake of ¹²³I- and ^99mTc-labelled tracers in an appropriate dose range in murine models targeting physiological processes in brain and heart. The thresholds of detection for differences in the tracer uptake determined under the conditions of our experiments well reflect distinctions in molar activity and uptake characteristics of the tracers. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Radiation dosimetry of <Emphasis Type="Italic">N</Emphasis>-([<Superscript>11</Superscript>C]methyl)benperidol as determined by whole-body PET imaging of primates

Purpose N-([¹¹C]methyl)benperidol ([¹¹C]NMB) can be used for positron emission tomography (PET) measurements of D₂-like dopamine receptor binding in vivo. We report the absorbed radiation dosimetry of i.v.-administered ¹¹C-NMB, a critical step before applying this radioligand to imaging studies in humans. Materials and methods Whole-body PET imaging with a CTI/Siemens ECAT 953B scanner was done in a male and a female baboon. After i.v. injection of 444–1221 MBq of ¹¹C-NMB, sequential images taken from the head to the pelvis were collected for 3 h. Volumes of interest (VOIs) were identified that entirely encompassed small organs (whole brain, striatum, eyes, and myocardium). Large organs (liver, lungs, kidneys, lower large intestine, and urinary bladder) were sampled by drawing representative regions within the organ volume. Time–activity curves for each VOI were extracted from the PET, and organ residence times were calculated by analytical integration of a multi-exponential fit of the time–activity curves. Human radiation doses were estimated using OLINDA/EXM 1.0 and the standard human model. Results Highest retention was observed in the blood and liver, each with total residence times of 1.5 min. The highest absorbed radiation doses were to the heart (10.5 mGy/kBq) and kidney (9.19 mGy/kBq), making these the critical organs for [¹¹C]NMB. A heart absorption of 50 mGy would result from an injected dose of 4,762 MBq [¹¹C]NMB. Conclusions Thus, this study suggests that up to 4,762 MBq of [¹¹C]NMB can be safely administered to human subjects for PET studies. Total body dose and effective dose for [¹¹C]NMB are 2.82 mGy/kBq and 3.7 mSv/kBq, respectively.     

Are restrictions to behaviour of patients required following fluorine-18 fluorodeoxyglucose positron emission tomographic studies?

The clinical use of positron emission tomography (PET) is expanding rapidly in most European countries. It is likely therefore that patients receiving the tracer fluorine-18 fluorodeoxyglucose (¹⁸FDG) will be discharged to come into contact with family members, members of the public and ward staff. There are few direct measurements on which to base any recommendations with regard to radiation protection, and so we have measured the dose rates from patients undergoing clinical PET examinations in our centre. Seventy-five patients who underwent whole-body and brain ¹⁸FDG PET examinations were studied. Dose rates were measured at 0.1, 0.5, 1.0 and 2.0 m from the mid thorax on leaving the department. The median administered activity was 323 MBq with a 95th percentile value of 360 MBq. The median dose rates measured at the four distances were 90.0, 35.0, 14.0 and 5.0 μSv h^–1 (the median dose rates per unit administered activity at 2 h post injection were 0.31, 0.11, 0.04 and 0.02 μSv h^–1 MBq^–1). The corresponding 95th percentile values were 174.0, 69.0, 29.0 and 7.5 μSv h^–1 (0.43, 0.2, 0.08 and 0.03 μSv h^–1 MBq^–1). A number of social situations were modelled and an annual dose limit of 1 mSv was used to determine whether restrictive behavioural advice was required. In the case of nursing staff on wards a value of 6 mSv was regarded as the annual limit, which translates to a daily limit of approximately 24 μSv. There is no need for restrictive advice for patients travelling by public or private transport when they leave the department 2 h after the administration of ¹⁸FDG. Similarly, there is no need for restrictive advice with regard to their contact with partners, work colleagues or children of any age, although it should be stressed that children should not accompany the patient to the scanning department. The only possible area of concern is in an oncology ward, where patients may be regularly referred for PET investigations and other high activity radionuclide studies and are partially helpless. Even in this area, however, it is unlikely that a nurse would receive a daily dose of more than 24 μSv. We conclude that there is no need for restrictive advice for patients undergoing ¹⁸FDG PET studies given the current administered activities. Received 27 July and in revised form 25 September 1998     

Radiation dosimetry and biodistribution of the translocator protein radiotracer [11C]DAA1106 determined with PET/CT in healthy human volunteers

IntroductionWhen microglia become activated (an integral part of neuroinflammation), cellular morphology changes and expression of translocator protein (TSPO) 18 kDa is increased. Over the past several years, [¹¹C]DAA1106 has emerged as a reliable radiotracer for labeling TSPO with high affinity during positron emission tomography (PET) scanning. While [¹¹C]DAA1106 PET scanning has been used in several research studies, a radiation dosimetry study of this radiotracer in humans has not yet been published.MethodsTwelve healthy participants underwent full body dynamic [¹¹C]DAA1106 PET scanning, with 8 sequential whole body scans (approximately 12 bed positions each), following a single injection. Regions of interest were drawn manually, and time activity curves (TACs) were obtained for 15 organs. OLINDA/EXM 1.1 was used to compute radiation absorbed doses to the target organs, as well as effective dose (ED) and effective dose equivalent (EDE).ResultsThe ED and EDE were 4.06 ± 0.58 μSv/MBq and 5.89 ± 0.83 μSv/MBq, respectively. The highest absorbed doses were to the heart wall, kidney, liver, pancreas, and spleen. TACs revealed that peak dose rates are during the first scan (at 6 min) for all organs other than the urinary bladder wall, which had its peak dose rate during the fourth scan (at 30 min).ConclusionsThe recently developed radiotracer [¹¹C]DAA1106 has its EDE and target-organ absorbed dose such that, for a single administration, its radiation dosimetry is well within the U.S. FDA guidelines for basic research studies in adults. This dose level implies that the dosimetry for multiple [¹¹C]DAA1106 scans within a given year also falls within FDA guidelines, and this favorable property makes this radiotracer suitable for examining microglial activation repeatedly over time, which may in the future be useful for longitudinal tracking of disease progression and monitoring of therapy response in conditions marked by neuroinflammation (e.g., head trauma and multiple sclerosis).     

Validation of a simplified carbon-14-urea breath test for routine use for detecting Helicobacter [correction of Heliobacter] pylori noninvasively

A carbon-14 (14C) urea breath test for detecting Helicobacter pylori with multiple breath sampling was developed. Carbon-14-urea (110 kBq) administered orally to 18 normal subjects and to 82 patients with Helicobacter infection. The exhaled 14C-labeled CO2 was trapped at 10-min intervals for 90 min. The total 14C activity exhaled over 90 min was integrated and expressed in %activity of the total dose given. In normals, a mean of 0.59% +/- 0.24% was measured, resulting in an upper limit of normal of 1.07%. In 82 patients, a sensitivity of 90.2%, a specificity of 83.8%, and a positive predictive value of 90.2% was found. The single probes at intervals of 40-60 min correlated best with the integrated result, with r ranging from 0.986 to 0.990. The test's diagnostic accuracy did not change at all when reevaluated with the 40-, 50-, or 60-min sample data alone. Thus, the 14C-urea breath test can be applied routinely as a noninvasive, low-cost and one-sample test with high diagnostic accuracy in detecting Helicobacter pylori colonization.     

Effect of deadtime loss on quantitative measurement of cerebral blood flow with technetium-99m hexamethylpropylene amine oxime

Deadtime count loss may cause error in quantitative measurements with a gamma camera. We evaluated the effect of deadtime loss on the measurement of cerebral blood flow (CBF). Radionuclide angiography with technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) was performed in 20 patients. A reference source was placed on the periphery of the detector to monitor deadtime loss, and CBF was calculated based on the data of radionuclide angiography with and without deadtime correction. In ten patients injected with 1110 MBq of the tracer, the CBF value without correction was 9.9%±1.8% higher than that with correction. This shows that deadtime loss may cause significant overestimation. The difference between CBF values obtained with and without correction was smaller in ten patients with an injected dose of 370 MBq (3.0%±1.2%). These results suggest a substantial effect of deadtime loss on CBF as measured by radionuclide angiography and ^99mTc-HMPAO. Received 14 July and in revised form 18 July 1997     

Detection of long-lived europium-152 in samarium-153-lexidronam

Samarium-153-lexidronam is a radiopharmaceutical used for pain palliation therapy in patients suffering from multilocular bone metastases. The postinjection residual of four pharmaceutical vials of ¹⁵³Sm-lexidronam and one patient were investigated for contamination with other isotopes using high-resolution gamma spectroscopy. In the spectra besides the already known contaminants europium-154, ¹⁵⁵Eu and ¹⁵⁶Eu, europium-152 was discovered in vitro and also in vivo. ¹⁵²Eu disintegrates with a half-life of 13.5 years emitting a multitude of high energy photons. Due to these properties, it does not only affect radioactive waste management regarding e.g. the disposal of the postinjection residual, but also poses an additional dose burden to the patient and to third persons. In the postinjection residual a mean activity concentration of 10.4±1.1 kBq europium-152 per GBq ¹⁵³Sm was detected. 62 days after isotope application, 15.8±4.0 kBq of ¹⁵²Eu were found within the patient. The lifetime effective dose to the patient from the europium impurities was determined using a multicompartment model. For ¹⁵²Eu the effective dose was 2.1 mSv/GBq ¹⁵³Sm-lexidronam and the total effective dose from all impurities was 6.1 mSv/GBq ¹⁵³Sm-lexidronam. The total absorbed dose to third persons caused by the europium impurities was estimated as 0.6 mGy/GBq ¹⁵³Sm-lexidronam.     

Biokinetics and dosimetry of 111In-DOTA-NOC-ATE compared with 111In-DTPA-octreotide

Purpose

The biokinetics and dosimetry of ¹¹¹In-DOTA-NOC-ATE (NOCATE), a high-affinity ligand of SSTR-2 and SSTR-5, and ¹¹¹In-DTPA-octreotide (Octreoscan?, OCTREO) were compared in the same patients.

Methods

Seventeen patients (10 men, 7 women; mean age 60?years), referred for an OCTREO scan for imaging of a neuroendocrine tumour (15), thymoma (1) or medullary thyroid carcinoma (1), agreed to undergo a second study with NOCATE. Whole-body anterior–posterior scans were recorded 0.5 (100?% reference scan), 4, 24 and 48?h (17 patients) and 120?h (5 patients) after injection. In 16 patients the OCTREO scan (178?±?15?MBq) was performed 16?±?5?days before the NOCATE scan (108?±?14?MBq) with identical timing; 1 patient had the NOCATE scan before the OCTREO scan. Blood samples were obtained from 14 patients 5?min to 48?h after injection. Activities expressed as percent of the initial (reference) activity in the whole body, lung, kidney, liver, spleen and blood were fitted to biexponential or single exponential functions. Dosimetry was performed using OLINDA/EXM.

Results

Initial whole-body, lung and kidney activities were similar, but retention of NOCATE was higher than that of OCTREO. Liver and spleen uptakes of NOCATE were higher from the start (p?<?0.001) and remained so over time. Whole-body activity showed similar α and β half-lives, but the β fraction of NOCATE was double that of OCTREO. Blood T _1/2β for NOCATE was longer (19 vs. 6?h). As a result, the effective dose of NOCATE (105?μSv/MBq) exceeded that of OCTREO (52?μSv/MBq), and the latter result was similar to the ICRP 106 value of 54?μSv/MBq. Differential activity measurement in blood cells and plasma showed an average of <5?% of NOCATE and OCTREO attached to globular blood components.

Conclusion

NOCATE showed a slower clearance from normal tissues and its effective dose was roughly double that of OCTREO.     

Biodistribution and radiation dosimetry in healthy volunteers of a novel tumour-specific probe for PET/CT imaging: BAY 85-8050

Purpose

Novel tracers for the diagnosis of malignant disease with PET and PET/CT are being developed as the most commonly used ¹⁸F deoxyglucose (FDG) tracer shows certain limitations. Employing radioactively labelled glutamate derivatives for specific imaging of the truncated citrate cycle potentially allows more specific tumour imaging. Radiation dosimetry of the novel tracer BAY 85-8050, a glutamate derivative, was calculated and the effective dose (ED) was compared with that of FDG.

Methods

Five healthy volunteers were included in the study. Attenuation-corrected whole-body PET/CT scans were performed from 0 to 90 min, at 120 and at 240 min after injection of 305.0?±?17.6 MBq of BAY 85-8050. Organs with moderate to high uptake at any of the imaging time points were used as source organs. Total activity in each organ at each time point was measured. Time–activity curves (TAC) were determined for the whole body and all source organs. The resulting TACs were fitted to exponential equations and accumulated activities were determined. OLINDA/EXM software was used to calculate individual organ doses and the whole-body ED from the acquired data.

Results

Uptake of the tracer was highest in the kidneys due to renal excretion of the tracer, followed by the pancreas, heart wall and osteogenic cells. The mean organ doses were: kidneys 38.4?±?11.2 μSv/MBq, pancreas 23.2?±?3.8 μSv/MBq, heart wall 17.4?±?4.1 μSv/MBq, and osteogenic cells 13.6?±?3.5 μSv/MBq. The calculated ED was 8.9?±?1.5 μSv/MBq.

Conclusion

Based on the distribution and dose estimates, the calculated radiation dose of BAY 85-8050 is 2.67?±?0.45 mSv at a patient dose of 300 MBq, which compares favourably with the radiation dose of FDG (5.7 mSv).     

Kinetics and dosimetry of iodine-131-labelled antibody fragments after local administration in patients with rectal cancer

In 11 patients with rectal cancer, a mixture of F(ab)₂ fragments of anti-carcinoembryonic antigen and anti-CA 19.9 labelled with a diagnostic dose of iodine-131 (3–10 MBq) was administered submucosally around the tumour. In this study, the local kinetics in and the dose to the rectal wall, the whole body kinetics and the effective dose equivalent are presented. The early disappearance of the activity from the injection spot was characterized by a T _1/2 of 21 h. Initially, about 50% of the plasma activity was due to free ¹³¹I. After 4 h, the plasma activity was almost completely protein bound (86%). Maximum plasma activity was observed after the 2nd day. From 72 h p.i., the plasma activity decreased with a T _1/2 of 53 h. In the first 24 h, 14% of the injected dose was excreted in the urine and within 4 days about half of the administered activity. The absorbed radiation dose to the rectal wall was estimated to be 0.2 Gy/MBq, presuming a 20 cm³ distribution volume. The dose to the bone marrow was 0.2 mGy/MBq or 0.4 mGy/MBq, assuming a homogeneous tracer distribution or equal blood and bone marrow activity concentrations, respectively. The effective dose equivalent is 1.9 mSv/MBq, mainly determined by the dose to the rectal wall and to a lesser extent by the dose to the remaining body. Postulating comparable kinetics, ¹²³I- or ¹¹¹In- or ^99mTc-labelled fragments would result in 4-25-fold lower effective dose equivalents. We conclude that the theoretical advantages of the local administration of ¹³¹I-labelled antibodies for diagnostic purposes in patients with rectal cancer are not limited by our dosimetric data. Nevertheless, we advocate the use of other radiolabels with more appropriate imaging qualities and probably a lower radiation burden. Offprint requests to: E.J. Derksen     

Whole-body kinetics and dosimetry ofl-3-[123I]iodo-α-methyltyrosine

The synthetic amino acidl-3-[¹²³I]iodo--methyltyrosine (IMT) is currently under clinical evaluation as a single-photon emission tomography (SPET) tracer of amino acid uptake in brain tumours. So far, dosimetric data in respect of IMT are not available. Therefore we investigated the whole-body distribution of IMT in six patients with cerebral gliomas and the radiation doses were estimated. Whole-body scans were acquired at 1.5, 3 and 5 h after i.v. injection of 370–550 MBq IMT. The bladder was voided prior to each scan and the radioactivity excreted in the urine was measured. Based on the MIRD-11 method and the updated MIRDOSE3, the mean absorbed doses for various organs and the effective dose were calculated from geometric means of the anterior and posterior whole-body scans using seven source organs and the residence time. IMT was predominantly excreted by the kidneys (52.8%±11.5% at 1.5 h p.i., 63.0%±15.7% at 3 h p.i. and 74.6%±9.8% at 5 h p.i.). No organ system other than the urinary tract showed significant retention of the tracer. Early whole-body scans revealed slightly increased tracer uptake in the liver and in the bowel. Highest absorbed doses were found for the urinary bladder wall (0.047 mGy/MBq), the kidneys (0.010 mGy/MBq), the lower large intestinal wall (0.011 mGy/MBq) and the upper large intestinal wall (0.008 mGy/MBq). The effective dose according to ICRP 60 was estimated to be 0.0073 mSv/MBq for adults. This leads to an effective dose of 3.65 mSv in a typical brain SPET study using 500 MBq IMT. The MIRDOSE3 scheme yielded similar results. Thus, in spite of the relatively high tracer dose required for optimal brain scanning, radiation exposure in SPET studies with IMT is in the normal range of routine nuclear medicine investigations.