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: [131I]sodium iodine, [18F]fludeoxyglucose, and [131I]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.

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.

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.

Adverse Events of Diagnostic Radiopharmaceuticals: A Systematic Review.

Diagnostic radiopharmaceuticals used in nuclear medicine can cause adverse events. Information on these adverse events is available in case reports and databases but may not be readily accessible to healthcare professionals. This systematic review provides an overview of adverse events of diagnostical radiopharmaceuticals and their characteristics. A median frequency for adverse events in diagnostical radiopharmaceuticals of 1.63 (interquartile range: 1.09-2.29) per 100,000 is reported. Most common are skin and subcutaneous tissue disorders, and general disorders and administration site conditions. Many adverse events reported are minor in severity, although 6.7% can be classified as important. In rare cases, adverse events are serious and potentially life-threatening. With the introduction of new radiopharmaceuticals and the increasing use of positron emission tomography-computed tomography, previously unknown adverse events may be detected in daily practice. Future work should cover the experience of the patient with adverse events from diagnostic radiopharmaceuticals.

Anaphylactic Reaction to Tc-99m Macrosalb.

A 49-year-old woman developed an anaphylactic reaction to Tc-99m macrosalb used for pulmonary scintigraphy. The patient received an intravenous injection of Tc-99m macrosalb 120 MBq, containing macroaggregates of human albumin 0.14 mg. Within 1 min she developed itching all over her body, an itching throat and dyspnoea. This was followed by urticaria and facial oedema. She was diagnosed with an anaphylactic shock. The patient received clemastine and prednisone, and fully recovered after release from the hospital. According to the Naranjo assessment algorithm, the relationship between the allergic reaction and the administration of Tc-99m macrosalb should be considered as 'probable'.

Radiopharmaceuticals in Acute Porphyria.

PURPOSE: The acute porphyrias are a group of rare metabolic disorders of the heme biosynthetic pathway. Carriers of the acute porphyria gene are prone to potentially fatal acute attacks, which can be precipitated by drug exposure. It is therefore important to know whether a drug is safe for carriers of the acute porphyria gene. In this study, radiopharmaceuticals were assessed on their porphyrogenicity (ie, the potential of a drug to induce an attack). METHODS: The assessment was conducted by classifying the drugs according to the Thunell model. FINDINGS: From 41 radiopharmaceuticals assessed, I-131 norcholesterol, Tc-99m mebrofenin, Tc-99m phytate, Tc-99m sestamibi, and Tl-201 chloride were classified as possibly porphyrogenic. IMPLICATIONS: I-131 norcholesterol, Tc-99m mebrofenin, Tc-99m phytate, Tc-99m sestamibi, and Tl-201 chloride should not be prescribed for patients experiencing acute porphyria unless an urgent indication is present and no safer alternative is available. In such cases, potential users should seek advice from a porphyria expert. Preventive measures may also be required.

Influence of proton-pump inhibitors on stomach wall uptake of 99mTc-tetrofosmin in cadmium-zinc-telluride SPECT myocardial perfusion imaging.

BACKGROUND: Proton-pump inhibitors (PPIs) induce potentially interfering stomach wall activity in single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) with technetium-99m ((99m)Tc)-sestamibi. However, no data are available for (99m)Tc-tetrofosmin. We assessed the influence of prolonged (>2 weeks) PPI use on the stomach wall uptake of (99m)Tc-tetrofosmin in patients referred for stress MPI with a cadmium-zinc-telluride-based SPECT camera and its relation with dyspepsia symptoms. METHODS AND RESULTS: Consecutive patients (n=127) underwent a 1-day adenosine stress-first SPECT-MPI with (99m)Tc-tetrofosmin, of whom 54 (43%) patients had been on PPIs for more than 2 weeks. Stomach wall activity was identified on stress SPECT using computed tomographic attenuation maps and was scored using a four-point grading scale into clinically relevant (scores 2 or 3) or nonrelevant (scores 0 or 1).Patients on PPIs had stomach wall uptake more frequently as compared with patients not using PPIs (22 vs. 7%, P=0.017). Dyspepsia was similar in both groups. CONCLUSION: Prolonged use of PPIs is associated with stomach wall uptake of (99m)Tc-tetrofosmin in stress cadmium-zinc-telluride-SPECT images. Gastric symptoms were not associated with stomach wall uptake.