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 ^99mTc-labelled radiopharmaceuticals, the total fraction of the administered activity excreted in the milk varied from 0.0057 % for ^99mTc-labelled red blood cells (RBC) to 19 % for ^99mTc-pertechnetate. The effective dose to an infant per unit activity administered to the mother ranged from 6.7?×?10^?6 mSv/MBq for ^99mTc-labelled RBC to 3.6?×?10^?2 mSv/MBq for ^99mTc-pertechnetate. For the other radiopharmaceuticals, the total fraction of administered activity excreted in the milk varied from 0.018 % (⁵¹Cr-EDTA) to 48 % (¹³¹I-NaI). The effective dose ranged from 5.6?×?10^?5 mSv_infant/MBq_mother (⁵¹Cr-EDTA) to 106 mSv_infant/MBq_mother (¹³¹I-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 ¹³¹I-NaI and interruption of feeding for 12 h for ¹²⁵I-iodohippurate, ¹³¹I-iodohippurate, ^99mTc-pertechnetate and ^99mTc-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.

     

Biological consequences of the heterogeneous irradiation of lymphocytes during technetium-99m hexamethylpropylene amine oxime white blood cell labelling

Technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) labelling of white blood cells, routinely used for the detection of infection, results in the incorporation of radioactivity by polymorphonuclear leucocytes and also lymphocytes and can induce cell lesions in the latter case. The aim of this study was therefore to acquire data on the morphological and functional status of labelled lymphocytes present in the ^99mTc-HMPAO leucocyte mixture and to determine the cellular consequences of labelling. The mean radioactivity associated with lymphocytes was 325±10.8 kBq/10⁶ lymphocytes under standard labelling conditions. Microautoradiographic studies showed that labelling was heterogeneous (4% intensely labelled cells), which prevented calculation of the mean absorbed dose. The frequency of chromosomal aberrations (dicentrics and rings) in the labelled lymphocytes for 380 kBq/10⁶ cells was 1.08±0.09 but no abnormality was observed in the unlabelled control lymphocytes. The plating efficiency of labelled lymphocytes was reduced, as compared with that for control cells, but some lymphocytes were still able to form clones and were still ”alive” by radiobiological definition. It is therefore suggested that lymphocytes should be removed from ^99mTc-HMPAO cell preparations before administration to patients. Received 9 March and in revised form 1 June 1998     

Technetium-99m and indium-111 double labelling of granulocytes for kinetic and clinical studies

A new technique of labelling granulocytes with both technetium-99m hexamethylpropylene amine oxime (HMPAO) and indium-111 in a single protocol was developed in order to exploit the advantages of each radiolabel in clinical and investigative studies. Fourteen patients were included in this prospective study. Granulocytes were labelled with both¹¹¹In-tropolonate and^99mTc-HMPAO. In vitro shape change assay and in vivo distribution and recovery studies were performed to assess the activation of and damage to these cells due to the labelling procedure. The comparative kinetics of¹¹¹In and^99mTc in the blood, liver, spleen, and bone marrow were studied by blood sampling and dual radionuclide imaging early (1 h) and late (24 h) after injection. The functional integrity of the double-labelled granulocytes and the feasibility of the technique were investigated in 14 patients with a painful prosthetic hip due to causes other than infection. The efficiency of double labelling was 63% (SD 14%) for¹¹¹In and 39% (SD 12%) for^99mTc-HMPAO. In vitro granulocyte activation and ex vivo recovery values were comparable to those from single radionuclide labelling. No artefactual granulocyte sequestration was seen in the lungs or liver. The radioactivity was distributed between the liver, spleen and bone marrow and, to a lesser extent, the lung. Early^99mTc counts in the liver, spleen and bone marrow, in relation to background, were significantly higher than¹¹¹In counts while the reverse was seen in late images. Furthermore, circulating free^99mTc was significantly higher than free¹¹¹In at 24 h. Organ^99mTc counts, expressed in relation to the activity in early images, decreased in the spleen, increased in the liver and remained unchanged in bone marrow, whereas¹¹¹In counts increased in the bone marrow and liver, and decreased in the spleen. Granulocytes can be labelled with both¹¹¹In and^99mTc-HMPAO in a single protocol without crosschelation, cellular activation or damage. By favourably exploiting their kinetics for early and late imaging, double-labelled granulocytes may be useful in several clinical and investigative situations.     

Upregulation of granulocyte CD11b (CR 3) after labelling with technetium-99m hexamethylpropylene amine oxime

Today technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) is widely used for leucocyte scintigraphy, as^99mTc-HMPAO selectively labels granulocytes in mixed leucocyte suspensions. However, the influence of cell labelling on the expression of specific adhesion proteins has not been studied before. Therefore, we investigated five patients, four of whom had established Crohn's disease. We found that leucocyte labelling with^99mTc-HMPAO induces increased expression of the glucoprotein receptor CD11b on granulocytes, but it is not clear whether this upregulation affects the functional integrity of the granulocytes.     

Simultaneous acquisition of <Superscript>99m</Superscript>Tc- and <Superscript>123</Superscript>I-labeled radiotracers using a preclinical SPECT scanner with CZT detectors

Objective

Simultaneous acquisition of ^99mTc and ¹²³I was evaluated using a preclinical SPECT scanner with cadmium zinc telluride (CZT)-based detectors.

Methods

10-ml cylindrical syringes contained about 37 MBq ^99mTc-tetrofosmin (^99mTc-TF) or 37 MBq ¹²³I-15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid (¹²³I-BMIPP) were used to assess the relationship between these SPECT radioactive counts and radioactivity. Two 10-ml syringes contained 100 or 300 MBq ^99mTc-TF and 100 MBq ¹²³I-BMIPP to assess the influence of ^99mTc upscatter and ¹²³I downscatter, respectively. A rat-sized cylindrical phantom also contained both 100 or 300 MBq ^99mTc-TF and 100 MBq ¹²³I-BMIPP. The two 10-ml syringes and phantom were scanned using a pinhole collimator for rats. Myocardial infarction model rats were examined using 300 MBq ^99mTc-TF and 100 MBq ¹²³I-BMIPP. Two 1-ml syringes contained 105 MBq ^99mTc-labeled hexamethylpropyleneamine oxime (^99mTc-HMPAO) and 35 MBq ¹²³I-labeled N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (¹²³I-FP-CIT). The two 1-ml syringes were scanned using a pinhole collimator for mice. Normal mice were examined using 105 MBq ^99mTc-HMPAO and 35 MBq ¹²³I-FP-CIT.

Results

The relationship between SPECT radioactive counts and radioactivity was excellent. Downscatter contamination of ¹²³I-BMIPP exhibited fewer radioactive counts for 300 MBq ^99mTc-TF without scatter correction (SC) in 125–150 keV. There was no upscatter contamination of ^99mTc-TF in 150–175 keV. In the rat-sized phantom, the radioactive count ratio decreased to 4.0 % for 300 MBq ^99mTc-TF without SC in 125–150 keV. In the rats, myocardial images and radioactive counts of ^99mTc-TF with the dual tracer were identical to those of the ^99mTc-TF single injection. Downscatter contamination of ¹²³I-FP-CIT was 4.2 % without SC in 125–150 keV. In the first injection of ^99mTc-HMPAO and second injection of ¹²³I-FP-CIT, brain images and radioactive counts of ^99mTc-HMPAO with the dual tracer in normal mice also were the similar to those of the ^99mTc-HMPAO single injection. In the first injection of ¹²³I-FP-CIT and second injection of ^99mTc-HMPAO, the brain images and radioactive counts with the dual tracer were not much different from those of the ¹²³I-FP-CIT single injection.

Conclusions

Dual-tracer imaging of ^99mTc- and ¹²³I-labeled radiotracers is feasible in a preclinical SPECT scanner with CZT detector. When higher radioactivity of ^99mTc-labeled radiotracers relative to ¹²³I-labeled radiotracers is applied, correction methods are not necessarily required for the quantification of ^99mTc- and ¹²³I-labeled radiotracers when using a preclinical SPECT scanner with CZT detector.

     

The excretion of radiopharmaceuticals in human breast milk: additional data and dosimetry

The amount of radioactivity excreted in breast milk following administration of 11 different radiopharmaceuticals, including technetium-99m labelled microspheres, pyrophosphate, diisopropyl-iminodiacetic acid (DISIDA) and sestamibi, has been measured. This report summarises the data collected from 60 patients. An effective decay constant for the series of samples from each patient was calculated from exponential curves fitted by least squares to the data. It is difficult to compare values from individual patients, since times of expression, volumes of milk and the activity administered are not uniform. In order to formulate reliable guidelines, we therefore calculated the total activity theoretically excreted in milk until complete decay of the radionuclide, which is usually higher than that actually measured over the actual period of collection. Of the various ^99mTc compounds, pertechnetate clearly reaches the highest concentrations in breast milk. The wide variability of data from different patients who received the same radiopharmaceutical despite identical methods of sample collection and data processing confirms the impression gained from literature that transfer of radionuclides into milk varies greatly between individuals. Although we have calculated average values for each compound, very large standard deviations were obtained, and we believe that for radiation protection purposes, a worst case approach is the most appropriate. With new data available and the revision of ICRP recommendations, the guidelines applicable when radiopharmaceuticals are administered to breast-feeding mothers are reviewed. The effective dose resulting from close contact between patient and infant was included in these calculations. Breast feeding need not be interrupted after administration of ^99mTc-DISIDA, -sulphur colloid, -gluconate and-methoxyisobutylisonitrile (MIBI). However, after administration of ^99mTc-MIBI, close contact should be restricted. ^99mTc-pyrophosphate and -microspheres require interruption periods of several hours. High activities of ^99mTc-pertechnetate may require interruption longer than 2 days. For pertechnetate and ^99mTc-labelled red blood cells, interruption of breast feeding with measurement of activity in expressed milk samples is recommended. Breast feeding is contra-indicated after administration of ⁶⁷Ga and ¹³¹I. General guidelines regarding breast feeding after administration of radiopharmaceuticals are summarised. Correspondence to: S. Rubow     

A quantitative approach to technetium-99m ethyl cysteinate dimer: a comparison with technetium-99m hexamethylpropylene amine oxime

To develop non-invasive regional cerebral blood flow (rCBF) measurements using technetium-99m ethyl cysteinate dimer (^99mTc-ECD) and single-photon emission tomography (SPET), the same graphical analysis as was described in our previous reports using technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) was applied to time-activity data for the aortic arch and brain hemispheres after intravenous injection of^99mTc-ECD. Hemispherical brain perfusion indices (BPI) for^99mTc-ECD showed a highly significant correlation (n = 22,r = 0.935,P = 0.0001) with those for^99mTc-HMPAO in 11 patients who underwent both tracer studies. Using both linear regression line equations between^99mTc-ECD BPI and^99mTc-HMPAO BPI and between^99mTc-HMPAO BPI and mean cerebral blood flow (CBF) values obtained from a xenon-133 inhalation SPET method in a previous study,^99mTc-ECD BPI was converted to¹³³Xe CBF values (y = 2.60x + 19.8). Then raw SPET images of^99mTc-ECD were converted to rCBF maps using Lassen's correction algorithm. In this algorithm, the correction factor a was fixed to 1.5, 2.6 and infinite. In the comparison of rCBF values for^99mTc-ECD SPET with those for^99mTc-HMPAO SPET in 396 regions of interest in the aforementioned 11 patients, the fixed correction factor of 2.6 gave nearly the same rCBF values for^99mTc-ECD (50.1 ± 16.9 ml/100 g/min, mean ± SD) as for^99mTc-HMPAO (49.9 ± 17.3 ml/100 g/min). In conclusion, the same non-invasive method as has been used in^99mTc-HMPAO studies is applicable to a^99mTc-ECD study for the measurement of rCBF without any blood sampling.     

Fetal dose estimates and the ICRP abdominal dose limit for occupational exposure of pregnant staff to technetium-99m and iodine-131 patients

The International Commission on Radiological Protection has recently recommended a supplementary dose limit of 2 mSv to the abdominal surface of a pregnant member of staff in order to provide protection to her fetus comparable to that in members of the public, whose annual limit is recommended to be 1 mSv. In order to determine whether this apparent attenuation factor of 50% is appropriate for nursing and imaging staff exposed to nuclear medicine patients, estimates were made of the ratios of the maternal abdominal surface to fetal dose appropriately weighted for time, distance and dose rate. Thermoluminescent dosimeter (TLD) measurements were made at various depths in an anthropomorphic phantom irradiated at different distances by a distributed source of either technetium-99m or iodine-131 in order to determine the corresponding attenuation factors at the average fetal midline depth. Dose estimates were based on these factors and on published values of dose rate and exposure times for nursing and imaging staff at these distances from the patient. Fetal doses to nursing staff caring for an adult^99mTc patient were estimated to vary from 86 Sv to 1.6 Sv, with the corresponding ratio of the abdominal surface to fetal dose varying from about 1.8:1 to 1.5:1 as the patient became less dependent on nursing care and the mean distance from the patient increased. Fetal doses to imaging staff varied from 1.12 Sv to 0.17 Sv for three types of^99mTc scan, but the ratio only varied from 1.4:1 to 1.3:1. Fetal doses to imaging staff were estimated to be 6.7 Sv and 9.0 Sv for a whole-body scan of a thyroid cancer patient after 1311 ablation and therapy respectively, and the ratio was 1.3:1 for both types of scan. It was concluded that for a pregnant ward nurse or imaging technologist exposed to an adult or paediatric patient administered^99mTc or¹³¹I, a dose limit of 1.3 mSv to the maternal abdominal surface will restrict their fetal dose to 1 mSv. A pregnant imaging technologist should perform no more than six adult^99mTc studies or one¹³¹I whole-body scan per day, and may have to wear a more sensitive personal dosimeter than a film badge.     

In vitro assessment of cytotoxicity and labeling efficiency of 99mTc-HMPAO with stromal vascular fraction of adipose tissue

IntroductionNoninvasive radionuclide imaging of cells using technetium99m-hexamethylpropyleneamine oxime (^99mTc-HMPAO) is a potential diagnostic tool for several applications. Herein we aimed to evaluate the labeling efficiency and cellular toxicity of ^99mTc-HMPAO with Stromal Vascular Fraction (SVF) of adipose tissue to develop a process tool for theranostic purposes, in particular imaging cardiac stem cell therapy.MethodsTen million cells of SVF were labeled with ^99mTc-HMPAO complex and excess radiolabel was cleared off through washing in PBS. The labeling efficiency of ^99mTc-HMPAO was detected in labeled cells and their subsequent supernatant wash using isotope dose calibrator and gamma camera. The cytotoxicity was assessed for the comparative reactive oxygen species (ROS) by H₂DCFDDA, apoptotic events by annexin-V and TUNEL assay and mitochondrial potential by JC-1.ResultsAn encouraging labeling efficiency of 33% was observed with ^99mTc-HMPAO complex. The radionuclide labeling of SVF demonstrated significant safety profile as evaluated by apoptotic assays.Conclusion^99mTc-HMPAO labeling efficiency of 33% of total SV fraction would produce sufficient radioactive signals that would enable for in vivo tracking of cells by SPECT-CT. The radionuclide did not demonstrate any significant impact on the structural or functional organization of the labeled cells. Our study indicates that SVF can be safely labeled with ^99mTc-HMPAO without adverse cytotoxic events and for its potential role in imaging cardiac stem cell therapy.     

Evaluation of patient effective dose from sentinel lymph node lymphoscintigraphy in breast cancer: a phantom study with SPECT/CT and ICRP-103 recommendations

Objective

To evaluate the effective dose delivered to patients undergoing sentinel lymph node (SLN) lymphoscintigraphy by taking into account both the transmission dose using the CT component of a SPECT/CT system and the ^99mTc internal emission dose.

Materials and methods

An adult female humanoid phantom and a set of thermoluminescent dosimeters were used in dose measurement from the CT transmission irradiation. The choice of measurement organs in the humanoid was guided by the recommendations described in the International Commission on Radiological Protection report number 103 (ICRP-103). The effective doses due to ^99mTc internal emission source were re-calculated from measurement data reported in our previous study on the same subject with the use of tissue weighting factors of ICRP-103.

Results

CT transmission dose is the main contribution to the patient total effective dose for both 1-day and 2-day lymphoscintigraphy protocols and for different surgical procedures. Patients undergoing SLN lymphoscintigraphy receive about the same amount of total effective dose of about 3 mSv for both 1-day and 2-day protocol, regardless of whether the tissues containing radioactivity would be excised at surgery or not.

Conclusion

Although the total effective dose from using SPECT/CT is equivalent to the annual natural background radiation of about 3 mSv, nuclear medicine physicians should be aware of the increase in effective dose for SLN lymphoscintigraphy using hybrid imaging technique of SPECT/CT when compared to conventional planar ⁵⁷Co flood source for transmission scan. Results from the current study provide update information in radiation exposure to patients undergoing SLN lymphoscintigraphy with the use of SPECT/CT.     

Uptake of technetium-99m hexamethylpropylene amine oxime labelled white cells in lymph nodes involved in non-Hodgkin's lymphoma

Radiolabelled white cell scanning is widely used to detect the presence of infection. We present a case of non-Hodgkin's lymphoma manifesting with signs and symptoms suggestive of infection, in which a technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) white cell scan demonstrated high uptake in lymph nodes involved by lymphoma. Differential cell analysis showed preferential lymphocyte labelling. The classification and management of the disease were changed accordingly. Our findings suggest that a future role for^99mTc-HMPAO labelled white cells in the assessment of disease activity of lymphoma should be investigated.     

Evaluation of technetium 99m cyclobutylpropylene amine oxime as a potential brain perfusion imaging agent for SPET

Technetium 99md,l-cyclobutylpropylene amine oxime (^99mTc-CBPAO) has been developed as a brain-imaging agent for single photon emission tomography (SPET).^99mTc-CBPAO can be prepared using a simple labelling procedure suitable for routine clinical use. It has a high in vitro stability, as has been demonstrated by high-pressure liquid chromatography (HPLC) analysis. This shows that 3 h after labelling, less than 5% of the primary lipophilic complex which is capable of crossing the blood-brain barrier (BBB) converts to a secondary hydrophilic complex. Brain uptake (% dose/g wet tissue) of^99mTc-CBPAO, determined at 5 and 30 min after injection in two groups of six adult male Sprague-Dawley rats, was found to be 0.74±0.06 and 0.73±0.13 (mean ± SD), respectively. These values are not significantly different from those obtained repeating the experiment with^99mTc-labelled hexamethylpropylene amine oxime (^99mTc-HMPAO) (0.72±0.15 at 5 min and 0.88 ± 0.24 at 30 min after injection). Since the rat brain uptake of^99mTc-CBPAO remained unchanged for a period of time suitable for tomographic study, the comparison of the two tracers was extended to two groups of ten patients. The latter were affected by neurological and psychiatric disorders and were studied with SPET. Human brain uptake (% dose/cc cortical grey matter) of^99mTc-CBPAO and^99mTc-HMPAO were 3.04±0.57 and 4.22±0.46 (mean × 10^–3 ± SD × 10^–3), respectively, with a 32% significant difference. In two other groups of five patients, the first transit time-activity curves of the two tracers were compared. From the analysis of these curves we suggest that^99mTc-CBPAO has a higher binding effect on blood components and/or a higher degradation rate in blood than that of^99mTc-HMPAO. This may account for the reduced human brain uptake. In conclusion, SPET images of^99mTc-CBPAO reflect blood perfusion, and they have a good diagnostic quality. The main advantage of^99mTc-CBPAO is its in vitro stability; however,^99mTc-HMPAO is a superior imaging agent.     

A multi-institutional study of interobserver agreement in the evaluation of dementia with rCBF/SPET technetium-99m exametazime (HMPAO)

Although specific patterns of technetium-99m exametazime [^99mTc-hexamethylpropylene amine oxime (HMPAO)] brain single-photon emission tomography (SPET) uptake have been described for patients with dementia, no multi-institutional study has evaluated interobserver agreement. Interobserver agreement for ^99mTc-HMPAO brain SPET uptake patterns in 50 clinically diagnosed demented subjects from four institutions were studied. Neurologists classified these subjects as presumed Alzheimer's disease (n=21), confirmed Alzheimers's disease (n=10), multi-infarct dementia (n=9), HIV-related dementia (n=7), or mixed (n=3). In addition 20 normal (five per institution) ^99mTc-HMPAO studies were included in a randomized blinded evaluation by three readers each from a different institution. Readers classified the general appearance of the images in one of four categories: normal, globally decreased uptake, focal areas of decreased uptake, and patchy changes in uptake. Consensus results show a sensitivity of 72% and specificity of 79% for identifying abnormalities in scans of demented subjects. Readers also rated ^99mTc-HMPAO uptake in eight designated regions in each hemisphere. Significant reader agreement (P < 0.01) for the classification by general appearance and the ratings of regional uptake was obtained. This study demonstrates that interpretation of regional cerebral blood flow/SPET images is concordant across multiple institutions and readers.Subject studies performed at St. Vincent's Hospital, New York     

Tc-99m-HMPAO labelled human platelets: in vitro and in vivo results

The lipophilic ^99mTc-HMPAO complex can be used for labelling platelets as well as granulocytes. Platelets were isolated according to standard isolation procedures for the evaluation of the optimal labelling parameters. The labelling efficiency (%) depends on incubation temperature (22° C: 40%; 37° C: 50%), incubation time (3 min: 20%, 25 min: 55%) and the incubation medium (plasma: 40%; saline 50%). The 60 min ^99mTc elution, out of the platelets ranged around 8%. The platelet recovery used as a quality control parameter is around 25%±4% and is stable for at least 240 min. The high elution rate out of the platelets leads to renal excretion of the label and hence to significant kidney and bladder activity. Intestinal excretion of the label can also be frequently demonstrated. Fresh thrombotic lesions can normally be detected 4 h after reinjection of the labelled platelets, and in some patients as early as 1 h after reinjection. In conclusion, ^99mTc-HMPAO seems to be a promising platelet label for imaging thrombotic lesions but not for platelet survival studies, because of the short physical half life of ^99mTc.Supported by the Deutsche Forschungsgemeinschaft (BE 1054/1–2)     

Current status of stress myocardial perfusion imaging pharmaceuticals and radiation exposure in Japan: Results from a nationwide survey

Background

Ionizing radiation generated during medical imaging procedures is a matter of concern. However, the current status of radiopharmaceutical use in stress myocardial perfusion imaging (MPI) and the radiation exposure from these radiopharmaceuticals is unknown in Japan.

Methods and Results

A nationwide survey was conducted from June through July 2016. The questionnaires on the radiopharmaceuticals used and their administered doses during stress MPI were sent to 641 nuclear medicine facilities. The responses were collected from 431 facilities and the effective dose (ED) for an adult with standard body weight was calculated. Forty-three percent of the facilities used only ²⁰¹TlCl, 35% used only ^99mTc radiopharmaceuticals, and the remaining 22% used both. The two main reasons for using ²⁰¹TlCl instead of ^99mTc radiopharmaceuticals were “more familiarity with the usage of ²⁰¹TlCl than ^99mTc radiopharmaceuticals” and “apprehension about increasing the burden of physicians performing tracer injection twice.” The mean ED was 14.0 ± 5.5 mSv (range, 3.9 to 25.2 mSv), which was higher than that reported in other countries.

Conclusions

The ED of stress MPI radiopharmaceuticals in Japan is probably higher than the world standard because more than 50% of the facilities still use ²⁰¹TlCl. We recommend revising the routine stress MPI protocol to reduce the effects of ionizing radiation.

     

The behavior of99mTc-hexamethylpropyleneamineoxime (99mTc-HMPAO) in blood and brain

^99mTc-hexamethylpropyleneamineoxime (^99mTc-HMPAO) is a reagent for scanning cerebral blood flow. We investigated how^99mTc-HMPAO changed in the blood and brain. The^99mTc-HMPAO, which was prepared by adding of^99mTcO _- ⁴ to HMPAO and Sn(II), consisted of primary and secondary complexes, reduced hydrolyzed^99mTc, and^99mTc0pertechnetate. The percentage of the primary complex in^99mTc-HMPAO decreased with time after preparation. The primary complex converted to the secondary one very rapidly in the presence of plasma. When^99mTc-HMPAO was injected into patients,^99mTc activity was immediately partitioned in the plasma fraction, with approximately 60% in whole blood. In plasma,^99mTc was found to be associated with proteins such as albumin and globulin.^99mTc trapped in red cells was not washed out with either plasma or saline. Biodistribution studies showed that the less lipophilic compounds of^99mTc-HMPAO could not pass through the blood brain barrier (BBB), and therefore did not accumulate in the brain. The results of gel chromatography and equilibrium dialysis indicated that no specific^99mTc binding protein was present in the brain. Considering the instability of^99mTc-HMPAO in vivo, we proposed that the speed at which the primary complex converted to the less lipophilic compounds was important in allowing^99mTc-HMPAO to pass through the BBB and to be fixed in the brain.     

The use of technetium-99m hexamethylpropylene amine oxime labelled white blood cells to detect subclinical inflammation of the heart after cardiopulmonary bypass in children with congenital heart disease

Ten children (6 boys and 4 girls, aged 1–9 years old) underwent operations with a cardiopulmonary bypass, and the technetium-99m hexamethylpropylene amine oxine (^99mTc-HMPAO) labelled white blood cell (WBC) heart scans were used to detect postoperative leukocyte infiltration in the hearts. The results showed that 80% (/810) of the cases had subclinical inflammation in the hearts (grading of WBC scans score 2), and a positive correlation (R = 0.77) was noted between the severity of the inflammation (grading of the WBC scans) and the duration of the cardiopulmonary bypass in the operations. Another control group (9 boys and 2 girls, aged 2–13 years old) underwent operations without a cardiopulmonary bypass, and subclinical inflammation of hearts was demonstrated in only 1 case (9%) by the ^99mTc-HMPAO labelled WBC scans (grading of WBC scans < score 2) after the operations. There was a significant difference (P < 0.001, by a Wilcoxon rank sum test) based upon the severity of the ischaemic heart damage in the two groups. In our preliminary conclusions, the ^99mTc-HMPAO labelled WBC heart scans may provide non-invasive and directly discernible evidence of subclinical inflammation in the heart due to a transient ischaemic state during a cardiopulmonary bypass, even if the clinical symptoms and signs of carditis are not apparent. Correspondence to: Chia-Hung Kao     

核医学检查受检者所受辐射剂量分析

目的 对核医学检查受检者所受辐射剂量进行测量和分析,以有效剂量表征受检者受到的辐射强度。方法 对核医学检查受检者进行分类,并测量计算所受放射性药物的辐射剂量,受检者所受计算机断层扫描(CT)辐射剂量,通过CT扫描参数和受检者信息等计算得到,上述两者相加换算得到受检者检查所受的有效剂量,并分析受检者所受辐射剂量的影响因素。结果 受检者正电子发射断层计算机成像(PET-CT)检查受到正电子放射性药物¹⁸F-氟代脱氧葡萄糖(¹⁸F-FDG)、¹⁸F-氟代胸苷(¹⁸F-FLT)、¹¹C-胆碱(¹¹C-choline)、¹¹C-蛋氨酸(¹¹C-MET)和¹¹C-乙酸盐(¹¹C-Ac)辐射所致有效剂量分别为(5.06±0.73)、(4.74±1.29)、(1.71±0.05)、(3.18±0.69)和(1.08±0.19)mSv;CT常规扫描辐射有效剂量为(8.80±0.58)mSv,若增加诊断CT扫描,接受的有效剂量可增大至27 mSv;单光子发射计算机断层成像(ECT)检查受到单光子放射性药物⁹⁹Tc^m-亚甲基二磷酸盐(⁹⁹Tc^m-MDP)、⁹⁹Tc^m-大颗粒聚合白蛋白(⁹⁹Tc^m-MAA)、⁹⁹Tc^m-二乙基三胺五乙酸(⁹⁹Tc^m-DTPA)、⁹⁹Tc^m-甲氧基异丁基异腈(⁹⁹Tc^m-MIBI)和⁹⁹Tc^m-焦磷酸盐(⁹⁹Tc^m-PYP)辐照所致的有效剂量分别为(4.63±0.01)、(1.71±0.01)、(1.18±0.01)、(7.19±0.03)和(4.18±0.01)mSv。结论 核医学检查受检者受到放射性药物辐射的有效剂量在1.08~7.19 mSv之间,PET-CT检查中CT所致有效剂量是8.80 mSv。     

Media Fill Test for validation of autologous leukocytes separation and labelling by 99mTc-HmPAO

ObjectiveManufacturing of sterile products must be carried out in order to minimize risks of microbiological contamination. White blood cells (WBC) labelled with ^99mTc-exametazime (^99mTc-hexamethylpropyleneamine oxime; ^99mTc-HMPAO) are being successfully applied in the field of infection/inflammation scintigraphy for many years. In our radiopharmacy lab, separation and labelling of autologous leukocytes with ^99mTc-HMPAO were performed in a laminar flow cabinet not classified and placed in a controlled area, whereas ^99mTc-HMPAO radiolabelling procedure was carried out in a hot cell with manipulator gloves. This study was conducted to validate this process using a Media Fill simulation test.MethodsThe study was performed using sterile Tryptic Soy Broth (TSB) in place of active product, reproducing as closely as possible the routine aseptic production process with all the critical steps, as described in the our internal standard operative procedures (SOP). The final vials containing the media of each processed step were then incubated for 14 days and examined for the evidence of microbial growth.ResultsNo evidence of turbidity was observed in all the steps assayed by the Media Fill.ConclusionsIn the separation and labelling of autologous leukocytes with ^99mTc-HmPAO, Media-Fill test represents a reliable tool to validate the aseptic process.     

Comparison of effective dose and lifetime risk of cancer incidence of CT attenuation correction acquisitions and radiopharmaceutical administration for myocardial perfusion imaging

Objective:

To measure the organ dose and calculate effective dose from CT attenuation correction (CTAC) acquisitions from four commonly used gamma camera single photon emission CT/CT systems.

Methods:

CTAC dosimetry data was collected using thermoluminescent dosemeters on GE Healthcare''s Infinia™ Hawkeye™ (GE Healthcare, Buckinghamshire, UK) four- and single-slice systems, Siemens Symbia™ T6 (Siemens Healthcare, Erlangen, Germany) and the Philips Precedence (Philips Healthcare, Amsterdam, Netherlands). Organ and effective dose from the administration of ^99mTc-tetrofosmin and ^99mTc-sestamibi were calculated using International Commission of Radiological Protection reports 80 and 106. Using these data, the lifetime biological risk was calculated.

Results:

The Siemens Symbia gave the lowest CTAC dose (1.8 mSv) followed by the GE Infinia Hawkeye single-slice (1.9 mSv), GE Infinia Hawkeye four-slice (2.5 mSv) and Philips Precedence v. 3.0. Doses were significantly lower than the calculated doses from radiopharmaceutical administration (11 and 14 mSv for ^99mTc-tetrofosmin and ^99mTc-sestamibi, respectively). Overall lifetime biological risks were lower, which suggests that using CTAC data posed minimal risk to the patient. Comparison of data for breast tissue demonstrated a higher risk than that from the radiopharmaceutical administration.

Conclusion:

CTAC doses were confirmed to be much lower than those from radiopharmaceutical administration. The localized nature of the CTAC exposure compared to the radiopharmaceutical biological distribution indicated dose and risk to the breast to be higher.

Advances in knowledge:

This research proved that CTAC is a comparatively low-dose acquisition. However, it has been shown that there is increased risk for breast tissue especially in the younger patients. As per legislation, justification is required and CTAC should only be used in situations that demonstrate sufficient net benefit.Single-photon emission CT (SPECT)/CT has become common place in clinical imaging, and a major role for CT is for the attenuation correction (AC) of SPECT data in myocardial perfusion imaging (MPI).^1,2 The benefits of CT attenuation correction (CTAC) in MPI are well known and many national and international professional organizations recommend its use to improve SPECT MPI diagnostic accuracy.^3,4 Associated with the CT acquisition is an additional radiation dose that is often considered to be low, yet very few articles quantify the dose and the associated risk.Effective dose is a useful figure that allows for a comparison between different techniques and protocols to be made. However, it is widely recognized that the tissue weighting factors are averaged over both genders and all ages, and therefore assessment and comparison of risk for an individual patient or patient group is not advised.^5–8 Lifetime risk of cancer incidence, sometimes referred to as lifetime biological risk is a concept that has been suggested by a number of authors as an alternative to effective dose (E) to allow a comparison of risk from non-uniform dose distributions.^5–7,9 Brenner^5–7 is arguably the strongest advocate for a move to what he terms “effective risk” as it is argued that E is based on “questionable science” as the tissue-specific weighting factors used, although based on research, are established by committee decisions and do not take into account differing age and gender dependencies. Wall et al¹⁰ similarly state that E can and should play a role in radiation protection of radiation workers and members of the public and for the optimization of techniques involving changes in radiation quality.The quality of the images generated by CTAC and the clinical evaluation of these to identify incidental extracardiac findings has been discussed in the literature.^11–13 Using phantom and human studies, it has been shown that CTAC data have the potential to allow a reporter to identify extracardiac pathology. The accuracy and confidence have been shown to vary with the protocols used. This study measured the organ dose and calculated the E from CTAC acquisitions from four different protocols. The protocols selected were those preset by manufacturers in four commonly used SPECT-CT scanners and were considered to be suitable to produce data of adequate quality to allow attenuation and scatter correction. The aim was to establish what differences in dose exist from the different protocols when the data produced are used for the same purpose. Using these data, the lifetime biological risk was calculated with a specific emphasis on the female breast. To contextualize these figures, organ, E and lifetime biological risks from the administration of radiopharmaceuticals (^99mTc-tetrofosmin and ^99mTc-sestamibi) were calculated from data contained in International Commission of Radiological Protection (ICRP) reports 80 and 106.^14,15 Comparisons were also made to estimated doses using the dose–length product (DLP) and published normalized values of effective dose per DLP.¹⁶