124I-L19-SIP for immuno-PET imaging of tumour vasculature and guidance of 131I-L19-SIP radioimmunotherapy

Purpose: The human monoclonal antibody (MAb) fragment L19-SIP is directed against extra domain B (ED-B) of fibronectin, a marker of tumour angiogenesis. A clinical radioimmunotherapy (RIT) trial with 131 I-L19-SIP was recently started. In the present study, after GMP production of 124 I and efficient production of 124 I-L19-SIP, we aimed to demonstrate the suitability of 124 I-L19-SIP immuno-PET for imaging of angiogenesis at early-stage tumour development and as a scouting procedure prior to clinical 131 I-L19-SIP RIT. Methods: 124 I was produced in a GMP compliant way via 124 Te(p,n) 124 I reaction and using a TERIMO™ module for radioiodine separation. L19-SIP was radioiodinated by using a modified version of the IODO-GEN method. The biodistribution of coinjected 124 I- and 131 I-L19-SIP was compared in FaDu xenograft-bearing nude mice, while 124 I PET images were obtained from mice with tumours of 90%, respectively. Tumour uptake was 7.3±2.1, 10.8±1.5, 7.8±1.4, 5.3±0.6 and 3.1±0.4%ID/g at 3, 6, 24, 48 and 72 h p.i., resulting in increased tumour to blood ratios ranging from 6.0 at 24 h to 45.9 at 72 h p.i.. Fully concordant labelling and biodistribu- tion results were obtained with 124 I- and 131 I-L19-SIP. Immuno-PET with 124 I-L19-SIP using a high-resolution research tomograph PET scanner revealed clear delineation of the tumours as small as 50 mm3 and no adverse uptake in other organs. Conclusions: 124 I-MAb conjugates for clinical immuno-PET can be efficiently produced. Immuno-PET with 124 I-L19-SIP appeared qualified for sensitive imaging of tumour neo- vasculature and for predicting 131 I-L19-SIP biodistribution.ISSN:1619-7070ISSN:1619-708

Role of endoscopic ultrasonography in the diagnostic work-up of idiopathic acute pancreatitis (PICUS):study protocol for a nationwide prospective cohort study

INTRODUCTION: Idiopathic acute pancreatitis (IAP) remains a dilemma for physicians as it is uncertain whether patients with IAP may actually have an occult aetiology. It is unclear to what extent additional diagnostic modalities such as endoscopic ultrasonography (EUS) are warranted after a first episode of IAP in order to uncover this aetiology. Failure to timely determine treatable aetiologies delays appropriate treatment and might subsequently cause recurrence of acute pancreatitis. Therefore, the aim of the Pancreatitis of Idiopathic origin: Clinical added value of endoscopic UltraSonography (PICUS) Study is to determine the value of routine EUS in determining the aetiology of pancreatitis in patients with a first episode of IAP. METHODS AND ANALYSIS: PICUS is designed as a multicentre prospective cohort study of 106 patients with a first episode of IAP after complete standard diagnostic work-up, in whom a diagnostic EUS will be performed. Standard diagnostic work-up will include a complete personal and family history, laboratory tests including serum alanine aminotransferase, calcium and triglyceride levels and imaging by transabdominal ultrasound, magnetic resonance imaging or magnetic resonance cholangiopancreaticography after clinical recovery from the acute pancreatitis episode. The primary outcome measure is detection of aetiology by EUS. Secondary outcome measures include pancreatitis recurrence rate, severity of recurrent pancreatitis, readmission, additional interventions, complications, length of hospital stay, quality of life, mortality and costs, during a follow-up period of 12 months. ETHICS AND DISSEMINATION: PICUS is conducted according to the Declaration of Helsinki and Guideline for Good Clinical Practice. Five medical ethics review committees assessed PICUS (Medical Ethics Review Committee of Academic Medical Center, University Medical Center Utrecht, Radboud University Medical Center, Erasmus Medical Center and Maastricht University Medical Center). The results will be submitted for publication in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: Netherlands Trial Registry (NL7066). Prospectively registered

Acute Clinical Manifestation of Mesenteric Heterotopic Pancreatitis: A Pre- and Postoperative Confirmed Case

Heterotopic pancreas is a relatively uncommon congenital anomaly, defined as pancreatic tissue in ectopic sites without an anatomic and vascular continuity with the main body of the pancreas. We report the case of a 58-year-old woman who was admitted to the hospital with the clinical suspicion of a mild, acute pancreatitis. Computed tomography, magnetic resonance imaging, transabdominal ultrasound, and endoscopic ultrasound revealed a normal orthotopic pancreas and the suspicion of a large heterotopic pancreas in the small bowel mesentery with signs of acute inflammation. The diagnosis of mesenteric heterotopic pancreatitis was preoperatively confirmed by endoscopic ultrasound-guided fine-needle aspiration and consequently histologically established after surgical resection

Managing patients with prediabetes and type 2 diabetes after coronary events: individual tailoring needed - a cross-sectional study

Background Understanding the determinants associated with prediabetes and type 2 diabetes in coronary patients may help to individualize treatment and modelling interventions. We sought to identify sociodemographic, medical and psychosocial factors associated with normal blood glucose (HbA1c < 5.7%), prediabetes (HbA1c 5.7–6.4%), and type 2 diabetes. Methods A cross-sectional explorative study applied regression analyses to investigate the factors associated with glycaemic status and control (HbA1c level) in 1083 patients with myocardial infarction and/or a coronary revascularization procedure. Data were collected from hospital records at the index event and from a self-report questionnaire and clinical examination with blood samples at 2–36 months follow-up. Results In all, 23% had type 2 diabetes, 44% had prediabetes, and 33% had normal blood glucose at follow-up. In adjusted analyses, type 2 diabetes was associated with larger waist circumference (Odds Ratio 1.03 per 1.0 cm, p = 0.001), hypertension (Odds Ratio 2.7, p < 0.001), lower high-density lipoprotein cholesterol (Odds Ratio 0.3 per1.0 mmol/L, p = 0.002) and insomnia (Odds Ratio 2.0, p = 0.002). In adjusted analyses, prediabetes was associated with smoking (Odds Ratio 3.3, p = 0.001), hypertension (Odds Ratio 1.5, p = 0.03), and non-participation in cardiac rehabilitation (Odds Ratio 1.7, p = 0.003). In patients with type 2 diabetes, a higher HbA1c level was associated with ethnic minority background (standardized beta [β] 0.19, p = 0.005) and low drug adherence (β 0.17, p = 0.01). In patients with prediabetes or normal blood glucose, a higher HbA1c was associated with larger waist circumference (β 0.13, p < 0.001), smoking (β 0.18, p < 0.001), hypertension (β 0.08, p = 0.04), older age (β 0.16, p < 0.001), and non-participation in cardiac rehabilitation (β 0.11, p = 0.005). Conclusions Along with obesity and hypertension, insomnia and low drug adherence were the major modifiable factors associated with type 2 diabetes, whereas smoking and non-participation in cardiac rehabilitation were the factors associated with prediabetes. Further research on the effect of individual tailoring, addressing the reported significant predictors of failure, is needed to improve glycaemic control. Trial registration Retrospectively registered at ClinicalTrials.gov: NCT02309255, December 5th 2014

Immuno-PET:A navigator in monoclonal antibody development and applications

Monoclonal antibodies (mAbs) have been approved for use as diagnostics and therapeutics in a broad range of medical indications, but especially in oncology. In addition, hundreds of new mAbs, engineered mAb fragments, and nontraditional antibody-like scaffolds directed against either validated or novel tumor targets are under development. Immuno positron emission tomography (PET), the tracking and quantification of mAbs with PET in vivo, is an exciting novel option to improve diagnostic imaging and to guide mAb-based therapy. In this review, recent technical advances leading to a jump ahead in mAb imaging are discussed. The availability of proper positron emitters, sophisticated radiochemistry, and advanced PET and PET-computed tomography scanners is crucial in these developments. Immuno-PET might play an important future role in cancer staging, in the improvement and tailoring of therapy with existing mAbs, and in the efficient development of novel mAbs. An overview of the preclinical and first clinical immuno-PET studies is provided