Administration Of Radiopharmaceuticals Research Articles

Preliminary quantitative evaluation of radiation-induced DNA damage in peripheral blood lymphocytes after cardiac dual-isotope imaging

DNA double-strand breaks (DSBs) of peripheral blood lymphocyte were prospectively assessed in 9 patients who were injected with 201Tl-chloride and 123I-beta-methyl-p-iodophenyl-pentadecanoic acid in dual-isotope imaging. Phosphorylated H2AX (γH2AX) was used as a biomarker for detecting DSBs, and the mean number of γH2AX foci per cell was measured microscopically. Mean γH2AX foci before administration of radiopharmaceuticals and at 3, 6, and 24 h following administration were 0.22 ± 0.34, 0.10 ± 0.14, 0.59 ± 0.46, and 0.52 ± 0.40, respectively (p = n.s. for all combinations).

Quality Improvement Initiatives to Assess and Improve PET/CT Injection Infiltration Rates at Multiple Centers.

PET/CT radiotracer infiltration is not uncommon and is often outside the imaging field of view. Infiltration can negatively affect image quality, image quantification, and patient management. Until recently, there has not been a simple way to routinely practice PET radiopharmaceutical administration quality control and quality assurance. Our objectives were to quantify infiltration rates, determine associative factors for infiltration, and assess whether rates could be reduced at multiple centers and then sustained. Methods: A “design, measure, analyze, improve, and control” quality improvement methodology requiring novel technology was used to try to improve PET/CT injection quality. Teams were educated on the importance of quality injections. Baseline infiltration rates were measured, center-specific associative factors were analyzed, team meetings were held, improvement plans were established and executed, and rates remeasured. To ensure that injection-quality gains were retained, real-time feedback and ongoing monitoring were used. Sustainability was assessed. Results: Seven centers and 56 technologists provided data on 5,541 injections. The centers’ aggregated baseline infiltration rate was 6.2% (range, 2%–16%). On the basis of their specific associative factors, 4 centers developed improvement plans and reduced their aggregated infiltration rate from 8.9% to 4.6% (P < 0.0001). Ongoing injection monitoring showed sustainability. Significant variation was found in center- and technologist-level infiltration rates (P < 0.0001 and P = 0.0020, respectively). Conclusion: A quality improvement approach with new technology can help centers measure infiltration rates, determine associative factors, implement interventions, and improve and sustain injection quality. Because PET/CT images help guide patient management, the monitoring and improvement of radiotracer injection quality are important.

Adaptation of hard gelatin capsules for oral delivery of aqueous radiopharmaceuticals.

Oral administration of Iodine-131 (I-131) solutions causes high risk of contamination for patients and dispensers. The objective of the study was to adapt hard gelatin capsules (HGCs) for filling with radiopharmaceutical solutions without deformation. Polystyrene (PS) internally lining films with different thicknesses were used to protect HGCs. The insulated HGCs were evaluated for their physicochemical characteristics and rupturing time in different dissolution media. HGCs internally lined with PS were examined for withstand loading with different volumes and radioactivities of I-131 solutions. Radioactivity release was studied in deionized water and acidic media. Quality control of released I-131 was inspected for radiochemical purities. There was a directly proportion between PS lining thickness and stability of HGCs after filling with 500μl aqueous methylene blue solution. HGCs internally lined with PS 100μm thickness withstand deformation for ˃ two months; however showed fast in-vitro rupturing time in different dissolution media. Internally lined HGCs loaded with different volumes and radioactivities of I-131 solutions resisted for one week without radioactive leakage. Yet, revealed complete release of I-131 after 20min in dissolution media with great radiochemical purity. The study promises safely I-131 aqueous solution delivery via adapted HGCs. Graphical abstract Oral administration of radiopharmaceuticals.

Patient dose reduction by changing the amount of 18F-FDG radiopharmaceutical injected

Images of Positron Emission Tomography (PET) associated with Computed Tomography (CT) have important diagnostic applications, mainly for oncology. These compound tomographic devices allow the overlapping of functional images obtained from the administration of radiopharmaceuticals and anatomical images generated by X-ray beam attenuation. This work evaluated the impact of reducing the effective dose by reducing the activity injected into the patient using the ICRP 106 biokinetic model. The activity to be injected may vary according to the patient mass and the detector sensitivity. In this work was used the fixed mass of Alderson phantoms, as a standard adult, this mass is 73.5 kg for the male, and 50 kg for the female. Different values of activity to be injected were simulated, from 0.07 mCi to 0.15 mCi per kg, and with 10 mCi fixed, protocol used in some services. Thus, for the acquisition of PET scans, any reduction of the administered activity implies a proportional reduction of the effective dose in patient. The effective dose may vary up to 114% altering the injected activity between 0.07 and 0.15 mCi. The fixed value of 10 mCi is between these variations. It is expected that the PET/CT scans protocols are changed at the end of the study, so that the absorbed and effective dose received by the patient decreases.

Introduction of radiopharmaceutical administration policy of FDA

Radiopharmaceuticals have been widely used in the diagnosis, treatment and monitoring of diseases, and they play an important role in new drug development. Food and Drug Administration(FDA) has rich experience in the administration of radiopharmaceuticals. This article mainly interprets the regulatory policy of FDA for radiopharmaceuticals from the aspects of definition, regulations and registration, trying to provide reference for domestic research of radiopharmaceuticals. Key words: Radiopharmaceuticals; United States Food and Drug Administration; Drug and narcotic control; Trends

Patient information poster for Nuclear Medicine

Patient information poster for Nuclear Medicine Patients attending a Nuclear Medicine department are generally unfamiliar with ionising radiation and Nuclear Medicine procedures. Nuclear Medicine staff are frequently questioned, and often it is the same concerns repeatedly raised. The IAEA currently have a patient information leaflet for patients attending for X-ray procedures [1] , however there is no similar leaflet available for Nuclear Medicine patients. A tertiary referral centre for Nuclear Medicine has created an information poster for patients answering some of the queries they may have while awaiting administration of radiopharmaceuticals. It is hoped this information will reinforce common verbal instructions given to patients, ensure compliance with these instructions and help alleviate concerns experienced by patients.

Radio-pharmaceuticals for cancer treatment: are they ready for prime time yet?

Radio-pharmaceuticals for cancer treatment: are they ready for prime time yet?

Activity estimation and biokinetic analysis of 99mTc-DMSA in renal infant patients using a gamma camera

Biokinetic data from the administration of radiopharmaceuticals is essential in nuclear medicine dosimetry. It has particular significance in children, as their metabolism is very different from adults. Biokinetic models for paediatric patients could therefore need to be adapted to better reflect their absorption, retention and excretion functions, when compared to adults. Obtaining quality in vivo infant or paediatric biokinetic data is then essential to improve the available reference models, which in turn can lead to the optimization of paediatric procedures and protocols in clinical practice.This study analyses the biokinetic behaviour of 99mTc-dimercaptosuccinic acid (DMSA), in 8 infants aged 4 months to 2 years old, through an imaging study using a gamma camera, and compares the obtained values with those obtained with the reference ICRP biokinetic model. The in vivo data was treated using an adapted methodology from the MIRD 16 pamphlet. Activity curves for the liver, the kidney and the whole body, were built, and new effective absorption, retention and excretion half-lives were estimated, and compared with the reference biokinetic parameters of ICRP 128. The obtained residence time in the kidneys of 2.56 h, has a deviation of 30.8% to the ICRP 128 value of 3.70 h. The obtained maximum uptake in the kidneys was of 0.22/A0, which compares to the value of 0.31/A0 for ICRP.The obtained biokinetic parameters were used to estimate the absorbed dose. The obtained dose values are smaller than the reference ICRP 128 ones by 32.1% in the kidneys, and 18.4% in the liver.

Assessment of radiopharmaceutical retention for vascular access ports using positron emission tomography imaging.

PurposeThe purpose of this study was to resolve the issue of whether various generations of CR Bard peripheral vascular access ports and catheters are prone to retain PET radiopharmaceuticals. The study evaluates the residual radioactivity remaining following injection for two PET radiopharmaceuticals currently used extensively in the clinic, FDG and Na18F.Methods FDG was purchased from a local cyclotron facility and Na18F was prepared in‐house. Three generations of currently marketed vascular access ports were tested. A total of five (n = 5) of each model was tested. Radiopharmaceutical of 2–3 mCi of each was injected into each port and flushed with 10, 30, 60, and 120 ml of saline. MicroPET scans were performed after each flush to detect the residual radioactivity on each port. A dose calibrator was used to detect the retention of radioactivity after each flush.ResultsRadioactivity retention for all vascular port models measured by microPET imaging was similar for both FDG and Na18F, with less than 1% residual activity following a 10 ml saline flush. Based on the microPET images, all the subsequent flushes of 30, 60, and 120 ml were also considered. Dose calibrator activity measurements validated microPET measurements as negligible for all the ports, even with the first 10 ml flush.ConclusionsMicroPET imaging was more sensitive than the dose calibrator in determining the radioactivity retention of the vascular access ports from CR Bard. These ports may be used for the injection of FDG and Na18F to track glucose metabolism and bone uptake with PET imaging. It is recommended to apply at least a 10 ml flush after radiopharmaceutical administration, to reduce residual activity to baseline levels.

DEVELOPMENT OF ALGORITHM OF THE RENAL HEMODYNAMICS ANALYSIS BY SCINTIGRAPHY

The aim of this work is the analysis of scintigraphic images of indirect renangiography of patients with chronic pyelonephritis. Indirect angiography is an auxiliary research methodology that is performed in the first seconds after intravenous administration of radio-pharmaceuticals. It allows to evaluate the temporal parameters of renal hemodynamics, to diagnose the presence of renal artery stenosis and to assess the level of vascularization of the kidney tumor.Scintigraphic images of indirect renangiography are characterized by low resolution. Therefore, effective perfusion of tissues is assessed by the kinetics of radiopharmaceuticals in the entire kidney. In this case, the kidney is represented as a concentrated system, that is, as a mathematical point. In turn, this leads to a loss of diagnostic information that characterizes the kidney as a spatially-distributed system.The paper describes the developed algorithm for analyzing the types of kinetic curves of radiopharmaceuticals in the kidneys and their further classification. The algorithm for the analysis of scintigraphic images of the kidneys according to renangioscintigraphy allows us to obtain additional useful information on the functional state of the renal parenchyma. This algorithm allows us to quantify the phenomenon of synchronization of the functional state of the nephron groups, which will provide fundamentally new diagnostic and important information to specialists in nuclear medicine and nephrologists

Radiation dose and risks to fetus from nuclear medicine procedures

This article discusses issues regarding administration of radiopharmaceuticals to pregnant women. Standardized dose estimates and possible biological effects on the unborn child are presented. Current and future mathematical models (phantoms) are discussed. Standardized dose estimates for pregnant women at several stages of gestation based on the current generation of phantoms are given. Issues related to administration of radioiodines, particularly 131I-NaI, are presented. Iodine concentrates in the fetal thyroid and therefore can give very high doses, even resulting in complete destruction of the fetal thyroid. Strategies for preventing unwanted administrations of radiopharmaceuticals to these patients, and for strategies for mitigating radiation doses, should an unwanted administration occur, are discussed.

The 38th Report on Survey of the Adverse Reaction to Radiopharmaceuticals (The 41st Survey in 2015).

This survey was performed to investigate the incidence of adverse reactions to radiopharmaceuticals in FY2015 in Japan. It was based on the responses to questionnaires sent to nuclear medicine institutions. The reply was obtained from 981 institutions among 1,274 to which the questionnaire had been sent. Fifteen cases of adverse reactions were reported. A total of 1,056,828 radiopharmaceutical administrations were reported. The incidence of adverse reactions per 100,000 cases was 1.4. No case of deficient products was reported.

Radiation dose produced by patients during radiopharmaceutical incorporation in nuclear medicine diagnostic procedures.

The aim of this study was to assess the dose received by members of the public due to close contact with patients undergoing nuclear medicine procedures during radiopharmaceutical incorporation, and comparing it with the emitted radiation dose when the test was complete, in order to establish recommendations. A prospective study was conducted on 194 patients. H*(10) dose rates were measured at 0.1, 0.5, and 1.0m after the radiopharmaceutical administration, before the image acquisition, and at the end of the nuclear medicine procedure. Effective dose for different close contact scenarios were calculated, according to 95th percentile value (bone scans) and the maximum value (remaining tests). During the radiopharmaceutical incorporation, a person who stays with another injected patient in the same waiting room may receive up to 0.59 mSv. If the patient had a medical appointment, or went to a restaurant or a coffee shop, members of the public could receive 23, 43, and 22 μSv, respectively. After finishing the procedure, these doses are reduced by a factor 3. In most of the studies, the use of private instead of public transport may reduce the dose by more than a factor 6. It is recommended to increase the distance between the patients during the radiopharmaceutical incorporation and to distribute them according to the diagnostic procedure. Patients should be encouraged to use private instead of public transport. Depending on the number of nuclear medicine outpatients per year attended by a physician, it could be necessary to apply restrictions.

Radiation dose produced by patients during radiopharmaceutical incorporation in nuclear medicine diagnostic procedures

ObjectivesThe aim of this study was to assess the dose received by members of the public due to close contact with patients undergoing nuclear medicine procedures during radiopharmaceutical incorporation, and comparing it with the emitted radiation dose when the test was complete, in order to establish recommendations. Material and methodsA prospective study was conducted on 194 patients. H*(10) dose rates were measured at 0.1, 0.5, and 1.0m after the radiopharmaceutical administration, before the image acquisition, and at the end of the nuclear medicine procedure. Effective dose for different close contact scenarios were calculated, according to 95th percentile value (bone scans) and the maximum value (remaining tests). ResultsDuring the radiopharmaceutical incorporation, a person who stays with another injected patient in the same waiting room may receive up to 0.59mSv. If the patient had a medical appointment, or went to a restaurant or a coffee shop, members of the public could receive 23, 43, and 22μSv, respectively. After finishing the procedure, these doses are reduced by a factor 3. In most of the studies, the use of private instead of public transport may reduce the dose by more than a factor 6. ConclusionIt is recommended to increase the distance between the patients during the radiopharmaceutical incorporation and to distribute them according to the diagnostic procedure. Patients should be encouraged to use private instead of public transport. Depending on the number of nuclear medicine outpatients per year attended by a physician, it could be necessary to apply restrictions.

Standardization of Administered Activities in Pediatric Nuclear Medicine: A Report of the First Nuclear Medicine Global Initiative Project, Part 2-Current Standards and the Path Toward Global Standardization.

The Nuclear Medicine Global Initiative (NMGI) was formed in 2012 and consists of 13 international organizations with direct involvement in nuclear medicine. The underlying objectives of the NMGI are to promote human health by advancing the field of nuclear medicine and molecular imaging, encourage global collaboration in education, and harmonize procedure guidelines and other policies that ultimately lead to improvements in quality and safety in the field throughout the world. For its first project, the NMGI decided to consider the issues involved in the standardization of administered activities in pediatric nuclear medicine. It was decided to divide the final report of this project into 2 parts. Part 1 was published in this journal in the spring of 2015. This article presents part 2 of the final report. It discusses current standards for administered activities in children and adolescents that have been developed by various professional organizations. It also presents an evaluation of the current practice of pediatric nuclear medicine specifically with regard to administered activities as determined by an international survey of 313 nuclear medicine clinics and centers from 29 countries. Lastly, it provides recommendations for a path toward global standardization of the administration of radiopharmaceuticals in children.

The 37th Report on Survey of the Adverse Reaction to Radiopharmaceuticals (the 40th Survey in 2014).

This survey was performed in order to investigate the incidence of adverse reactions to radiopharmaceuticals in FY2014 in Japan. It was based on the responses to questionnaires sent to nuclear medicine institutions. The reply was obtained from 992 institutions among 1,244 to which the questionnaire had been sent. Nine cases of adverse reactions were reported. A total of 1,091,011 radiopharmaceutical administrations were reported. The incidence of adverse reactions per 100,000 case was 0.8. Three cases of deficient products were reported, and the incidence of deficient products per 100,000 case was 0.3.

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

To review early recommendations and propose guidelines for breastfeeding interruption after administration of radiopharmaceuticals, based on additional biokinetic and dosimetric data. 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. 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). 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.

Radiological Justification for and Optimization of Nuclear Medicine Practices in Korea.

Nuclear medicine is a rapidly growing discipline that employs advanced novel hybrid techniques that provide unique anatomical and functional information, as well as targets for molecular therapy. Concomitantly, there has been an increase in the attention paid to medical radiation exposure. A radiological justification for the practice of nuclear medicine has been implemented mainly through referral guidelines based on research results such as prospective randomized clinical trials. The International Commission on Radiological Protection recommends diagnostic reference levels as a practical mechanism to optimize medical radiation exposure in order to be commensurate with the medical purpose. The Korean Society of Nuclear Medicine has been implementing radiological optimization through a survey of the protocols on how each hospital determines the dose of administration of each radiopharmaceutical. In the case of nuclear medicine, radiation exposure of caregivers and comforters of patients discharged after administration of therapeutic radiopharmaceuticals can occur; therefore, optimization has been implemented through written instructions for patients, based on international recommendations. The development of patient-radiation-dose monitoring software, and a national registry and management system of patient-radiation-dose is needed to implement radiological optimization through diagnostic reference levels. This management system must work in agreement with the “Institute for Quality Management of Nuclear Medicine”, and must take into account the medical reality of Korea, such as low medicine fee, in order to implement reasonable radiological justification and optimization.

Possibilities of the exposure reduction of hands during the preparation and application of radiopharmaceuticals

The current routinely used methods of estimating the skin equivalent dose relies on the finger dosimetry which usually largely underestimates the real maximum exposure and thus appropriate correction factors have to be used. The group under the investigation consisted of 10 workers preparing and 5 workers administering radiopharmaceuticals labelled with 18F. The monitoring was carried out using 12 pairs of thermoluminiscent dosimeters (TLDs) placed on each hand of the worker. A total of 46 measurements were completed. The maximum exposure of the skin of hands, defined in terms of the quantity of the personal dose equivalent Hp(0.07), was related to the unit activity of radiopharmaceutical with which the worker came into the contact during the measurement. The exposure of the hands of workers handling 18F-labelled radiopharmaceuticals showed significant inhomogeneity. Out of 15 workers, in 53 % of cases, the maximum skin exposure was observed on the tip of their index finger. It was estimated that in about 60 % of the cases (during the preparation and administration of radiopharmaceuticals), the exposure may exceed the 3/10 of the annual dose limit. Moreover, in 40 % of all cases, the exposure may even be higher than this dose limit. The established relevant correction factors reached the values up to 8 (as for preparations) and 13 (as for administrations). The study resulted in the establishment of the appropriate correction factors and in the recommendations of procedures aimed at the further reduction of the exposure of extremities (Tab. 3, Fig. 2, Ref. 17).

Radiation-synthesized protein-based drug carriers: Size-controlled BSA nanoparticles

Nanotechnology has broadened the options for the delivery of agents of biotechnological and clinical relevance. Currently, attention has been driven towards the development of protein-based nanocarriers due to high the biocompatibility and site-specific delivery. In this work we report radiation-synthesized bovine serum albumin nanoparticles as an attempt to overcome limitations of available albumin particles, as a novel route for the development of crosslinked protein nanocarriers for the administration of chemotherapic agents or radiopharmaceuticals. Albumin containing phosphate buffer solutions were irradiated using γ-irradiation at distinct cosolvent concentrations—ethanol or methanol. Nanoparticle size was followed by DLS and bityrosine crosslinking formation using fluorescence measurements and SDS-PAGE. In addition, computational experiments were performed to elucidate the mechanism and pathways for the nanoparticle formation. The synthesis of BSA nanoparticles using γ-irradiation in the presence of a cosolvent allowed the formation of the nanoparticles from 7 to 70nm without the use of any chemical crosslinker as confirmed by SDS-PAGE and DLS analysis. The combination of cosolvent and γ-irradiation allowed a fine tuning with regard to protein size.