The current role of nuclear medicine in breast cancer

Breast cancer is the most common cancer in females worldwide. Nuclear medicine plays an important role in patient management, not only in initial staging, but also during follow-up. Radiopharmaceuticals to study breast cancer have been used for over 50 years, and several of these are still used in clinical practice, according to the most recent guideline recommendations. In this critical review, an overview of nuclear medicine procedures used during the last decades is presented. Current clinical indications of each of the conventional nuclear medicine and PET/CT examinations are the focus of this review, and are objectively provided. Radionuclide therapies are also referred, mainly summarising the methods to palliate metastatic bone pain. Finally, recent developments and future perspectives in the field of nuclear medicine are discussed. In this context, the promising potential of new radiopharmaceuticals not only for diagnosis, but also for therapy, and the use of quantitative imaging features as potential biomarkers, are addressed. Despite the long way nuclear medicine has gone through, it looks like it will continue to benefit clinical practice, paving the way to improve healthcare provided to patients with breast cancer.</p

Segmenting Critical Factors for Enhancing the use of IT in Humanitarian Supply Chain Management

AbstractThis study intends to explore and segment the critical factors (CFs) to enhance the use of Information Technology (IT) in Humanitarian Supply Chain (HSC), particularly in the Indian context. In this study, ten influencing factors has been identified through an extensive literature review and expert opinion. A structural model and cause–effect relationship diagram was developed using decision-making trial and evaluation laboratory (DEMATEL) method for the identification of CFs. The present study adopt a comprehensive and rigorous procedure to identify six CFs namely, top management support, Government support, feedback mechanism to facilitate learning from prior experiences, transparent and accountable supply chain, strategic planning, and mutual learning with other commercial organizations (COs). The developed framework provides a simple, effective and efficient way to enhance the utilization of IT in HSC and in large to improve the competencies and performance of HSC

Setting-up a training programme for intraoperative molecular imaging and sentinel node mapping: how to teach? How to learn?

BackgroundThe current expansion of image-guided surgery is closely related to the role played by radio-guided surgery in supporting the sentinel node (SN) procedure during more than three decades. The so-called triple approach (lymphoscintigraphy, gamma probe detection and blue dye) was not only essential in the seminal validation of the SN procedure but also a first collective learning effort based on skill transfer and outcome-related evaluation which laid the fundaments to delineate the field of intraoperative molecular imaging (IMI) based on a similar multimodality approach and multidisciplinary practice.MethodsThese elements are also becoming valid in the current incorporation of SPECT/CT and PET/CT to existing and new protocols of IMI procedures and SN mapping concerning other clinical applications. On the other hand, there is a growing tendency to combine novel modern technologies in an allied role with gamma guidance in the operating room following the development of hybrid tracers and multimodal detection approaches. Against this background, learning initiatives are required for professionals working in this area.ResultsThis objective has led to a group of European practitioners with large experience in SN mapping and IMI applications to give shape to a programme made up out of specific learning modules aimed to be used as a conductive thread in peripherical or centralised training instances concerning the topic.ConclusionThe presented work, written as a tutorial review, is placed in an available prior-art context and is primarily aimed at medical and paramedical practitioners as well as at hardware and software developers.Radiolog

The clinical impact of molecular breast imaging in women with proven invasive breast cancer scheduled for breast-conserving surgery

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Stimulation of the beta-2-adrenergic receptor with salbutamol activates human brown adipose tissue

While brown adipose tissue (BAT) is activated by the beta-3-adrenergic receptor (ADRB3) in rodents, in human brown adipocytes, the ADRB2 is dominantly present and responsible for noradrenergic activation. Therefore, we performed a randomized double-blinded crossover trial in young lean men to compare the effects of single intravenous bolus of the ADRB2 agonist salbutamol without and with the ADRB1/2 antago-nist propranolol on glucose uptake by BAT, assessed by dynamic 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography scan (i.e., primary outcome). Salbutamol, compared with salbutamol with propranolol, increases glucose uptake by BAT, without affecting the glucose uptake by skeletal muscle and white adipose tissue. The salbutamol-induced glucose uptake by BAT positively asso-ciates with the increase in energy expenditure. Notably, participants with high salbutamol-induced glucose uptake by BAT have lower body fat mass, waist-hip ratio, and serum LDL-cholesterol concentration. In conclusion, specific ADRB2 agonism activates human BAT, which warrants investigation of ADRB2 activation in long-term studies (EudraCT: 2020-004059-34).NWO091506191007

Clinical impact of molecular breast imaging as adjunct diagnostic modality in evaluation of indeterminate breast abnormalities and unresolved diagnostic concerns

Purpose Improvements in molecular breast imaging (MBI) have increased the use of MBI as adjunct diagnostic modality and alternative to MRI. We aimed to assess the value of MBI in patients with equivocal breast lesions on conventional imaging, especially in terms of its ability to rule out malignancy. Methods We selected patients who underwent MBI in addition to conventional diagnostics due to equivocal breast lesions between 2012 and 2015. All patients underwent digital mammography, target ultrasound and MBI. MBI was performed using a single-head Dilon 6800 gamma camera after administration of 600 MBq 99mTc-sestamibi. Imaging was reported according to BI-RADS classification and compared with pathology or follow-up of ≥6 months. Results Of 226 women included, pathology was obtained in 106 (47%) and (pre)malignant lesions were found in 25 (11%). Median follow-up was 5.4 years (IQR 3.9-7.1). Sensitivity was higher for MBI compared to conventional diagnostics (84% vs. 32%; P = 0.002), identifying malignancy in 21 and 6 patients, respectively, but specificity did not differ (86% vs. 81%; P = 0.161). Positive and negative predictive value were 43% and 98% for MBI and 17% and 91% for conventional diagnostics. MBI was discordant with conventional diagnostics in 68 (30%) patients and correctly changed diagnosis in 46 (20%) patients, identifying 15 malignant lesions. In subgroups with nipple discharge (N = 42) and BI-RADS 3 lesions (N = 113) MBI detected 7 of 8 occult malignancies. Conclusion MBI correctly adjusted treatment in 20% of patients with diagnostic concerns after conventional work-up, and could rule out malignancy with a high negative predictive value of 98%.</p

The impact of using BARCIST 1.0 criteria on quantification of BAT volume and activity in three independent cohorts of adults

Human brown adipose tissue (BAT) is commonly assessed by cold-induced 18F-fluorodeoxyglucose (FDG) PET-CT using several quantification criteria. Uniform criteria for data analysis became available recently (BARCIST 1.0). We compared BAT volume and activity following BARCIST 1.0 criteria against the most commonly used criteria [Hounsfield Units (HU):-250, -50, standardized uptake value (SUV):2.0; HU: Not applied, SUV:2.0 and HU:-180, -10, SUV:1.5] in a prospective study using three independent cohorts of men including young lean adults, young overweight/obese adults and middle-aged overweight/obese adults. BAT volume was the most variable outcome between criteria. While BAT volume calculated using the HU: NA; SUV: 2.0 criteria was up to 207% higher than the BAT volume calculated based on BARCIST 1.0 criteria, it was up to 57% lower using the HU: -250, -50; SUV: 2.0 criteria compared to the BARCIST 1.0. Similarly, BAT activity (expressed as SUVmean) also differed between different thresholds mainly because SUVmean depends on BAT volume. SUVpeak was the most consistent BAT outcome across the four study criteria. Of note, we replicated these findings in three independent cohorts. In conclusion, BAT volume and activity as determined by 18F-FDG-PET/CT highly depend on the quantification criteria used. Future human BAT studies should conduct sensitivity analysis with different thresholds in order to understand whether results are driven by the selected HU and/or SUV thresholds. The design of the present study precludes providing any conclusive threshold, but before more definitive thresholds for HU and SUV are available, we support the use of BARCIST 1.0 criteria to facilitate interpretation of BAT characteristics between research groups

The impact of using BARCIST 1.0 criteria on quantification of BAT volume and activity in three independent cohorts of adults

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

⁸⁹Zr-Trastuzumab PET/CT Imaging of HER2-Positive Breast Cancer for Predicting Pathological Complete Response after Neoadjuvant Systemic Therapy:A Feasibility Study

Background: Approximately 20% of invasive ductal breast malignancies are human epidermal growth factor receptor 2 (HER2)-positive. These patients receive neoadjuvant systemic therapy (NAT) including HER2-targeting therapies. Up to 65% of patients achieve a pathological complete response (pCR). These patients might not have needed surgery. However, accurate preoperative identification of a pCR remains challenging. A radiologic complete response (rCR) on MRI corresponds to a pCR in only 73% of patients. The current feasibility study investigates if HER2-targeted PET/CT-imaging using Zirconium-89 (89Zr)-radiolabeled trastuzumab can be used for more accurate NAT response evaluation. Methods: HER2-positive breast cancer patients scheduled to undergo NAT and subsequent surgery received a 89Zr-trastuzumab PET/CT both before (PET/CT-1) and after (PET/CT-2) NAT. Qualitative and quantitative response evaluation was performed. Results: Six patients were enrolled. All primary tumors could be identified on PET/CT-1. Four patients had a pCR and two a pathological partial response (pPR) in the primary tumor. Qualitative assessment of PET/CT resulted in an accuracy of 66.7%, compared to 83.3% of the standard-of-care MRI. Quantitative assessment showed a difference between the SUVR on PET/CT-1 and PET/CT-2 (ΔSUVR) in patients with a pPR and pCR of −48% and −90% (p = 0.133), respectively. The difference in tumor-to-blood ratio on PET/CT-1 and PET/CT-2 (ΔTBR) in patients with pPR and pCR was −79% and −94% (p = 0.133), respectively. Three patients had metastatic lymph nodes at diagnosis that were all identified on PET/CT-1. All three patients achieved a nodal pCR. Qualitative assessment of the lymph nodes with PET/CT resulted in an accuracy of 66.7%, compared to 50% of the MRI. Conclusions: NAT response evaluation using 89Zr-trastuzumab PET/CT is feasible. In the current study, qualitative assessment of the PET/CT images is not superior to standard-of-care MRI. Our results suggest that quantitative assessment of 89Zr-trastuzumab PET/CT has potential for a more accurate response evaluation of the primary tumor after NAT in HER2-positive breast cancer.</p

Effect of sitagliptin on energy metabolism and brown adipose tissue in overweight individuals with prediabetes:a randomised placebo-controlled trial

Aims/hypothesis: The aim of this study was to evaluate the effect of sitagliptin on glucose tolerance, plasma lipids, energy expenditure and metabolism of brown adipose tissue (BAT), white adipose tissue (WAT) and skeletal muscle in overweight individuals with prediabetes (impaired glucose tolerance and/or impaired fasting glucose). Methods: We performed a randomised, double-blinded, placebo-controlled trial in 30 overweight, Europid men (age 45.9 \xc2\xb1 6.2\xc2\xa0years; BMI 28.8 \xc2\xb1 2.3\xc2\xa0kg/m2) with prediabetes in the Leiden University Medical Center and the Alrijne Hospital between March 2015 and September 2016. Participants were initially randomly allocated to receive sitagliptin (100\xc2\xa0mg/day) (n = 15) or placebo (n = 15) for 12\xc2\xa0weeks, using a randomisation list that was set up by an unblinded pharmacist. All people involved in the study as well as participants were blinded to group assignment. Two participants withdrew from the study prior to completion (both in the sitagliptin group) and were subsequently replaced with two new participants that were allocated to the same treatment. Before and after treatment, fasting venous blood samples and skeletal muscle biopsies were obtained, OGTT was performed and body composition, resting energy expenditure and [18F] fluorodeoxyglucose ([18F]FDG) uptake by metabolic tissues were assessed. The primary study endpoint was the effect of sitagliptin on BAT volume and activity. Results: One participant from the sitagliptin group was excluded from analysis, due to a distribution error, leaving 29 participants for further analysis. Sitagliptin, but not placebo, lowered glucose excursion (\xe2\x88\x9240%; p < 0.003) during OGTT, accompanied by an improved insulinogenic index (+38%; p < 0.003) and oral disposition index (+44%; p < 0.003). In addition, sitagliptin lowered serum concentrations of triacylglycerol (\xe2\x88\x9229%) and very large (\xe2\x88\x9246%), large (\xe2\x88\x9235%) and medium-sized (\xe2\x88\x9224%) VLDL particles (all p < 0.05). Body weight, body composition and energy expenditure did not change. In skeletal muscle, sitagliptin increased mRNA expression of PGC1\xce\xb2 (also known as PPARGC1B) (+117%; p < 0.05), a main controller of mitochondrial oxidative energy metabolism. Although the primary endpoint of change in BAT volume and activity was not met, sitagliptin increased [18F] FDG uptake in subcutaneous WAT (sWAT; +53%; p < 0.05). Reported side effects were mild and transient and not necessarily related to the treatment. Conclusions/interpretation: Twelve weeks of sitagliptin in overweight, Europid men with prediabetes improves glucose tolerance and lipid metabolism, as related to increased [18F] FDG uptake by sWAT, rather than BAT, and upregulation of the mitochondrial gene PGC1\xce\xb2 in skeletal muscle. Studies on the effect of sitagliptin on preventing or delaying the progression of prediabetes into type 2 diabetes are warranted. Trial registration: ClinicalTrials.gov NCT02294084. Funding: This study was funded by Merck Sharp & Dohme Corp, Dutch Heart Foundation, Dutch Diabetes Research Foundation, Ministry of Economic Affairs and the University of Granada