Patient-Reported Adverse Events of Radiopharmaceuticals:A Prospective Study of 1002 Patients

Introduction Adverse events of radiopharmaceuticals may be underreported or remain undetected. Patients can provide information about these adverse events to enable healthcare professionals to detect, understand, and manage them more efficiently. Objective In this study, we aimed to (a) determine the type, causality, and frequency of patient-reported adverse events of radiopharmaceuticals and to (b) assess the onset, outcome, and follow-up of these adverse events from the patient's perspective. Methods We performed a prospective cohort study of 1002 patients who underwent a nuclear medicine examination. Using a validated questionnaire, we collected patient-reported information on adverse events that occurred immediately after administration of the radiopharmaceutical as well as those that occurred later. Adverse events were analysed, coded and assessed for causality by two independent researchers. Results A total of 187 (18.7%) patients reported 379 adverse events. Most patient-reported adverse events of radiopharmaceuticals belonged to the 'general disorder and administration site conditions' (42.0%) and 'nervous system disorders' (16.9%) system organ classes. Of the patient-reported adverse events, 43.0% were possibly or probably causally related to radiopharmaceuticals. We found the frequency of patient-reported adverse drug reactions to diagnostic radiopharmaceuticals to be 2.8%. No important medical events were related to the administrations of diagnostic radiopharmaceuticals. Most adverse events (80.0%) occurred shortly after administration of the radiopharmaceutical and were resolved within a few hours. Some events (20.0%) emerged after patients had left the nuclear medicine department, took longer to resolve, and sometimes prompted the patient to consult a healthcare professional. Conclusion Adverse reactions to diagnostic radiopharmaceuticals can occur, and the frequency reported by patients was found to be 2.8%, which is higher than reported in the existing literature. We hope that the results of this study increase awareness of these adverse reactions among patients and healthcare professionals

Safe use of radiopharmaceuticals in patients with chronic kidney disease:A systematic review

BACKGROUND: Patients with chronic kidney disease (CKD) may need to have their radiopharmaceutical dosage adjusted to prevent adverse effects and poor outcomes, but there are few recommendations on radiopharmaceutical dosing for this group of patients. The aim of this study is to provide an overview of the available information on radiopharmaceutical dose recommendations for patients with CKD. METHODS: We performed a systematic literature review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We conducted a literature search in the MEDLINE (PubMed) and Embase databases and screened potentially relevant studies using inclusion and exclusion criteria. We independently assessed the included observational studies’ methodologies and extracted relevant data. RESULTS: Of the 5795 studies first identified, 34 were included in this systematic review. These studies described three radiopharmaceuticals: [(131)I]sodium iodine, [(18)F]fludeoxyglucose, and [(131)I]iobenguane. Twenty-nine studies (85.3%) reported data on patients with CKD stage 5, while only three studies mentioned CKD patients in other stages (8.8%). CONCLUSION: We found no consistent recommendations for radiopharmaceutical dosing in patients with CKD. Although some studies do mention dosing difficulties in patients with CKD, information is available for only a few radiopharmaceuticals, and recommendations are sometimes contradictory. Further research on radiopharmaceutical dosing in patients with CKD is needed to determine whether these patients require specific dosing, especially for therapeutic radiopharmaceuticals where a non-optimised dose may lead to an increased risk of toxicity for non-targeted organs. Including patients with CKD in studies and providing specific information about dosing in these patients should be a priority for the radiopharmaceutical community

Current generation time-of-flight 18F-FDG PET/CT provides higher SUVs for normal adrenal glands, while maintaining an accurate characterization of benign and malignant glands

OBJECTIVE: Modern PET/CT scanners have significantly improved detectors and fast time-of-flight (TOF) performance and this may improve clinical performance. The aim of this study was to analyze the impact of a current generation TOF PET/CT scanner on standardized uptake values (SUV), lesion-background contrast and characterization of the adrenal glands in patients with suspected lung cancer, in comparison with literature data and commonly used SUV cut-off levels. METHODS: We included 149 adrenal glands from 88 patients with suspected lung cancer, who underwent (18)F-FDG PET/CT. We measured the SUV(max) in the adrenal gland and compared this with liver SUV(mean) to calculate the adrenal-to-liver ratio (AL ratio). Results were compared with literature derived with older scanners, with SUV(max) values of 1.0 and 1.8 for normal glands [1, 2]. Final diagnosis was based on histological proof or follow-up imaging. We proposed cut-off values for optimal separation of benign from malignant glands. RESULTS: In 127 benign and 22 malignant adrenal glands, SUV(max) values were 2.3 ± 0.7 (mean ± SD) and 7.8 ± 3.2 respectively (p < 0.01). Corresponding AL ratios were 1.0 ± 0.3 and 3.5 ± 1.4 respectively (p < 0.01). With a SUV(max) cut-off value of 3.7, 96 % sensitivity and 96 % specificity was reached. An AL ratio cut-off value of 1.8 resulted in 91 % sensitivity and 97 % specificity. The ability of both SUV(max) and AL ratio to separate benign from malignant glands was similar (AUC 0.989 vs. 0.993, p = 0.22). CONCLUSIONS: Compared with literature based on the previous generation of PET scanners, current generation TOF (18)F-FDG PET/CT imaging provides higher SUVs for benign adrenal glands, while it maintains a highly accurate distinction between benign and malignant glands. Clinical implementation of current generation TOF PET/CT requires not only the use of higher cut-off levels but also visual adaptation by PET readers

Discontinuation of metformin to prevent metformin-induced high colonic FDG uptake:is 48 h sufficient?

Objective: In this retrospective, single-center observational study, we investigated whether discontinuing metformin for at least 48 h prevents metformin-induced [18F]fluorodeoxyglucose (FDG) uptake in all segments of the colon. Methods: Patients with type 2 diabetes who were using metformin before undergoing an FDG PET/CT scan were included. Two groups were created: patients who discontinued metformin for less than 48 h (< 48 h group) and patients who discontinued metformin for between 48 and 72 h (≥ 48 h group). A control group comprised non-diabetic patients who were not using metformin before undergoing an FDG PET/CT. We visually scored the uptake of FDG in four segments of the colon—the ascendens, transversum, descendens, and rectosigmoid—using a four-point scale (1–4) and considered scores of 3 or 4 to be clinically significant. Results: Colonic FDG uptake in the ≥ 48 h group (n = 23) was higher than uptake in the control group (n = 96) in the colon descendens [odds ratio (OR) 14.0; 95% confidence interval (CI) 4.8–40.9; p value: 0.001] and rectosigmoid (OR 11.3; 95% CI 4.0–31.9; p value: 0.001), and there was no difference in the colon ascendens and transversum. Colonic FDG uptake in the < 48 h group (n = 25) was higher than uptake in the ≥ 48 h group (n = 23) in the colon transversum (OR 4.8; 95% CI 1.3–18.5; p value: 0.022) and rectosigmoid (p value: 0.023), and there was no difference in the colon ascendens and descendens. Conclusions: Discontinuing metformin for 48 h before undergoing an FDG PET/CT still gives a high uptake in the distal parts of the colon when compared with non-diabetic patients who are not using metformin. Discontinuing metformin for 48 h seems to be useful for scanning the more proximal segments of the colon

Patient-Reported Adverse Events of Radiopharmaceuticals:Development and Validation of a Questionnaire

Introduction Radiopharmaceuticals may cause adverse events. Knowledge about adverse events from a patient's perspective could help healthcare professionals to detect, understand, and manage adverse events more efficiently when using radiopharmaceuticals. Researchers need a validated questionnaire that can be used in patients to assess adverse events with radiopharmaceuticals. Objective The aim of this study was to develop, validate the content of, and perform initial testing of a questionnaire assessing patient-reported adverse events of radiopharmaceuticals. Methods Based on existing literature, six professionals drafted and evaluated a first version of the questionnaire. Further content validation was performed using cognitive interviews with six patients undergoing a nuclear medicine examination. After adaptations, the questionnaire was developed into a web-based questionnaire. One hundred patients undergoing nuclear examination tested this version, and the results were used to assess its acceptability and evaluate reported adverse events. Results Questions and answer options were revised in the initial questionnaire to improve clarity. In addition, some questions were removed. The final version consisted of 18 questions. In the test phase, the acceptability of the questionnaire was demonstrated (e.g. 79% of the patients who received the questionnaire completed it, and the median time to complete the questionnaire was 12 min for patients who reported an adverse event). Of the 100 patients (53% men, median age 64 years), 12 reported a total of 22 adverse events. One of these adverse events had a high causal association. Conclusion After validation and testing, the developed questionnaire to study patient-reported adverse events of radiopharmaceuticals is a suitable and valid instrument which can be used in future research

Impact of new X-ray technology on patient dose in pacemaker and implantable cardioverter defibrillator (ICD) implantations

PURPOSE: New X-ray technology providing new image processing techniques may reduce radiation exposure. The aim of this study was to quantify this radiation exposure reduction for patients during pacemaker and implantable cardioverter defibrillator (ICD) implantation. METHODS: In this retrospective study, 1185 consecutive patients who had undergone de novo pacemaker or ICD implantation during a 2-year period were included. All implantations in the first year were performed using the reference technology (Allura Xper), whereas in the second year, the new X-ray technology (AlluraClarity) was used. Radiation exposure, expressed as the dose area product (DAP), was compared between the two time periods to determine the radiation exposure reduction for pacemaker and ICD implantations without cardiac resynchronization therapy (CRT) and with CRT. Procedure duration and contrast volume were used as measures to compare complexity and image quality. RESULTS: The study population consisted of 591 patients who had undergone an implantation using the reference technology, and 594 patients with the new X-ray technology. The two groups did not differ in age, gender, or body mass index. The DAP decreased with 69 % from 16.4 ± 18.5 to 5.2 ± 6.6 Gy cm(2) for the non-CRT implantations (p < 0.001). The DAP decreased with 75 % from 72.1 ± 60.0 to 17.8 ± 17.4 Gy cm(2) for the CRT implantations (p < 0.001). Nevertheless, procedure duration and contrast volume did not differ when using the new technology (p = 0.09 and p = 0.20, respectively). CONCLUSIONS: Introduction of new X-ray technology resulted in a radiation exposure reduction of more than 69 % for patients during pacemaker and ICD implantation while image quality was unaffected

Non-adherence to consensus guidelines on preoperative imaging in surgery for primary hyperparathyroidism

Objective: The aim of this study was to determine the adherence to consensus guidelines on preoperative imaging of patients with primary hyperparathyroidism (pHPT) in real local practice. Methods: This was a retrospective multicenter cohort study of 411 patients undergoing parathyroidectomy for pHPT from 2007 to 2017 in three referral centers. Results: In 286/411 patients (69%) the preoperative imaging workup adhered to guidelines (utilizing ultrasound and parathyroid scintigraphy). In patients in whom guidelines were followed 63% were discharged within one day versus 37% in whom guidelines were not followed (P< .0005). The use of a bimodality imaging workup, starting with ultrasound and parathyroid scintigraphy followed by imaging upscaling aiming for anatomical and functional concordance, was a predictor for the performance of a minimally invasive parathyroidectomy (OR 4.098, 95% CI 2.296-7.315,P< .0005). Conclusion: The level of compliance to preoperative imaging guidelines is suboptimal in this population. Patients in whom adherence was achieved showed a shorter length of stay. More education of physicians is required regarding the appropriate preoperative imaging workup in pHPT

Selectivity of F-18-FLT and F-18-FDG for differentiating tumor from inflammation in a rodent model

Increased glucose metabolism of inflammatory tissues is the main source of false-positive F-18-FDG PET findings in oncology. It has been suggested that radiolabeled nucleosides might be more tumor specific. Methods: To test this hypothesis, we compared the biodistribution of 3'-deoxy-3'-F-18-fluorothymidine (FLT) and F-18-FDG in Wistar rats that bore tumors (C6 rat glioma in the right shoulder) and also had sterile inflammation in the left calf muscle (induced by injection of 0.1 mL of turpentine). Twenty-four hours after turpentine injection, the rats received an intravenous bolus (30 MBq) of either F-18-FLT (n = 5) or F-18-FDG (n = 5). Pretreatment of the animals with thymidine phosphorylase (>1,000 U/kg, intravenously) before injection of F-18-FLT proved to be necessary to reduce the serum levels of endogenous thymidine and achieve satisfactory tumor uptake of radioactivity. Results: Tumor-to-muscle ratios of F-18-FDG at 2 h after injection (13.2 +/- 3.0) were higher than those of F-18-FLT (3.8 +/- 1.3). F-18-FDG showed high physiologic uptake in brain and heart, whereas F-18-FLT was avidly taken up by bone marrow. F-18-FDG accumulated in the inflamed muscle, with 4.8 +/- 1.2 times higher uptake in the affected thigh than in the contralateral healthy thigh, in contrast to F-18-FLT, for which this ratio was not significantly different from unity (1.3 +/- 0.4). Conclusion; In F-18-FDG PET images, both tumor and inflammation were visible, but F-18-FLT PET showed only the tumor. Thus, the hypothesis that F-18-FLT has a higher tumor specificity was confirmed in our animal model

Selectivity of F-18-FLT and F-18-FDG for differentiating tumor from inflammation in a rodent model

Increased glucose metabolism of inflammatory tissues is the main source of false-positive F-18-FDG PET findings in oncology. It has been suggested that radiolabeled nucleosides might be more tumor specific. Methods: To test this hypothesis, we compared the biodistribution of 3'-deoxy-3'-F-18-fluorothymidine (FLT) and F-18-FDG in Wistar rats that bore tumors (C6 rat glioma in the right shoulder) and also had sterile inflammation in the left calf muscle (induced by injection of 0.1 mL of turpentine). Twenty-four hours after turpentine injection, the rats received an intravenous bolus (30 MBq) of either F-18-FLT (n = 5) or F-18-FDG (n = 5). Pretreatment of the animals with thymidine phosphorylase (>1,000 U/kg, intravenously) before injection of F-18-FLT proved to be necessary to reduce the serum levels of endogenous thymidine and achieve satisfactory tumor uptake of radioactivity. Results: Tumor-to-muscle ratios of F-18-FDG at 2 h after injection (13.2 +/- 3.0) were higher than those of F-18-FLT (3.8 +/- 1.3). F-18-FDG showed high physiologic uptake in brain and heart, whereas F-18-FLT was avidly taken up by bone marrow. F-18-FDG accumulated in the inflamed muscle, with 4.8 +/- 1.2 times higher uptake in the affected thigh than in the contralateral healthy thigh, in contrast to F-18-FLT, for which this ratio was not significantly different from unity (1.3 +/- 0.4). Conclusion; In F-18-FDG PET images, both tumor and inflammation were visible, but F-18-FLT PET showed only the tumor. Thus, the hypothesis that F-18-FLT has a higher tumor specificity was confirmed in our animal model