Biokinetics and dosimetry of commonly used radiopharmaceuticals in diagnostic nuclear medicine – a review

Purpose The impact on patients’ health of radiopharmaceuticals in nuclear medicine diagnostics has not until now been evaluated systematically in a European context. Therefore, as part of the EU-funded Project PEDDOSE. NET (www.peddose.net), we review and summarize the current knowledge on biokinetics and dosimetry of commonly used diagnostic radiopharmaceuticals. Methods A detailed literature search on published biokinetic and dosimetric data was performed mostly via PubMed (www.ncbi.nlm.nih.gov/pubmed). In principle the criteria for inclusion of data followed the EANM Dosimetry Committee guidance document on good clinical reporting. Results Data on dosimetry and biokinetics can be difficult to find, are scattered in various journals and, especially in paediatric nuclear medicine, are very scarce. The data collection and calculation methods vary with respect to the time-points, bladder voiding, dose assessment after the last data point and the way the effective dose was calculated. In many studies the number of subjects included for obtaining biokinetic and dosimetry data was fewer than ten, and some of the biokinetic data were acquired more than 20 years ago. Conclusion It would be of interest to generate new data on biokinetics and dosimetry in diagnostic nuclear medicine using state-of-the-art equipment and more uniform dosimetry protocols. For easier public access to dosimetry data for diagnostic radiopharmaceuticals, a database containing these data should be created and maintained

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

High intratumoural accumulation of stealth® liposomal doxorubicin (Caelyx®) in glioblastomas and in metastatic brain tumours

The blood-brain barrier is a major obstacle for the chemotherapeutic drugs to effectively reach primary or secondary brain tumours, Stealth® liposomal drugs are highly accumulated in tumoural tissues. In the present study we investigated the relative accumulation of 99mTc-DTPA radiolabelled stealth® liposomal doxorubicin (Caelyx®) in 10 patients with metastatic brain tumours and five patients with brain glioblastoma undergoing radiotherapy. Patients with metastatic brain lesions were treated with 10 consecutive fractions of radiotherapy (whole brain, 3 Gy/fraction, day 1-12) followed by a booster dose of 9 Gy (3 Gy/fraction, day 21-23), Caelyx®, at a dose of 25 mg mg -2 was given on day 1 and on day 21. Radiolabelled Caelyx® accumulation was 13-19 times higher in the glioblastomas and 7-13 times higher in the metastatic lesions, as compared to the normal brain. The drug accumulation in the tumoural areas was 40-60% of the accumulation in the bone marrow of the skull bones. The normal brain radioactivity was &lt;4% of the bone marrow, confirming an important shielding effect of the blood-brain barrier in the normal but not in the tumoural tissue. Four of 10 patients with metastatic lesions showed a complete response in CT-scan performed 2 months following therapy. There was no severe toxicity related to radiotherapy or to chemotherapy noted. It is concluded that stealth® liposomal drugs selectively overcome the blood-brain barrier in the tumoural areas. The clinical importance of this observation is now under investigation. (C) 2000 Cancer Research Campaign

Role of scintigraphy in inflammatory bowel disease

The diagnosis of inflammatory bowel disease (IBD) depends on direct endoscopic visualization of the colonic and ileal mucosa and the histological study of the obtained samples. Radiological and scintigraphic methods are mainly used as an adjunct to endoscopy. In this review, we focus on the diagnostic potential of nuclear medicine procedures. The value of all radiotracers is described with special reference to those with greater experience and more satisfactory results. Tc-99m hexamethylpropylene amine oxime white blood cells remain a widely acceptable scintigraphic method for the diagnosis of IBD, as well as for the evaluation of disease extension and severity. Recently, pentavalent Tc-99m dimercaptosuccinic acid has been recommended as an accurate variant and a complementary technique to endoscopy for the follow-up and assessment of disease activity. Positron emission tomography alone or with computed tomography using fluorine-18 fluorodeoxyglucose appears to be a promising method of measuring inflammation in IBD patients

Is 99mTc-LeucoScan scintigraphy useful in the assessment of location in Crohn's disease?

Background/Aims: Scintigraphy with 99mTechnetium HMPAO labelled whitw blood cells (99mTC HMPAO-WBC) is routinely used for the assessment of inflammatory bowel disease (IBD). The main disadvantages of this diagnostic test, are the time consuming in vitro cell labelling and the handling of blood Itself. To overcome these problem, new, equally effective agents are under development. To assess the value of a new easily prepared agen, the 99mTc-Leucoscan, in IBD, we performed a pilot scintigraphic study in patients with active Crohn's disease (CD). In the event of negaative results, it was envisaged, that another agent 99mTc (V) dimercaptosuccinic acid (DMSA) would be tested. Patients - Method: We performed 99mTc-Leucoscan scintigraphy in 7 patients with clinically active CD and in 3 of them an additional scintigraphy, th 99mTc (V) DMSA. Two of the 7 patients were males and 5 females; aged 26-70 years (mean age 42 years). Two of them had extra-intestinal manifestations with joint involvement. Results: In one of these patients 99mTc-Leucoscan scintigraphy was considered as indetermenate because of relatively increased uptake in the bowel and in the other 6 it was false negative. In the 2 patients with joint involvement 99mTc-Leucoscan images did show increased uptake in the involved bone areas. Three of all patients subsequently underwent 99mTc (V) DMSA scintigraphy and all 3 were considered true positive. Conclusion: Our study concludes that 99mTc-Leucoscan scintigraphy has no place in the assessment of gastrointestinal inflammation in CD. 99mTc (V) DMSA could be suggested as a reliable tracer that could substitute for 99mTc-HMPAO WBC scintigraphy in IBD patients

miRNA Regulons Associated with Synaptic Function

Differential RNA localization and local protein synthesis regulate synapse function and plasticity in neurons. MicroRNAs are a conserved class of regulatory RNAs that control mRNA stability and translation in tissues. They are abundant in the brain but the extent into which they are involved in synaptic mRNA regulation is poorly known. Herein, a computational analysis of the coding and 3'UTR regions of 242 presynaptic and 304 postsynaptic proteins revealed that 91% of them are predicted to be microRNA targets. Analysis of the longest 3'UTR isoform of synaptic transcripts showed that presynaptic mRNAs have significantly longer 3'UTR than control and postsynaptic mRNAs. In contrast, the shortest 3'UTR isoform of postsynaptic mRNAs is significantly shorter than control and presynaptic mRNAs, indicating they avert microRNA regulation under specific conditions. Examination of microRNA binding site density of synaptic 3'UTRs revealed that they are twice as dense as the rest of protein-coding transcripts and that approximately 50% of synaptic transcripts are predicted to have more than five different microRNA sites. An interaction map exploring the association of microRNAs and their targets revealed that a small set of ten microRNAs is predicted to regulate 77% and 80% of presynaptic and postsynaptic transcripts, respectively. Intriguingly, many of these microRNAs have yet to be identified outside primate mammals, implicating them in cognition differences observed between high-level primates and non-primate mammals. Importantly, the identified miRNAs have been previously associated with psychotic disorders that are characterized by neural circuitry dysfunction, such as schizophrenia. Finally, molecular dissection of their KEGG pathways showed enrichment for neuronal and synaptic processes. Adding on current knowledge, this investigation revealed the extent of miRNA regulation at the synapse and predicted critical microRNAs that would aid future research on the control of neuronal plasticity and etiology of psychiatric diseases