Publications by authors named "Wolfgang Mohnike"

9 Publications

  • Page 1 of 1

Novel Radiolabeled Bisphosphonates for PET Diagnosis and Endoradiotherapy of Bone Metastases.

Pharmaceuticals (Basel) 2017 May 18;10(2). Epub 2017 May 18.

Institute of Nuclear Chemistry, Johannes Gutenberg University Mainz, Fritz-Strassmann-Weg 2, 55128 Mainz, Germany.

Bone metastases, often a consequence of breast, prostate, and lung carcinomas, are characterized by an increased bone turnover, which can be visualized by positron emission tomography (PET), as well as single-photon emission computed tomography (SPECT). Bisphosphonate complexes of Tc are predominantly used as SPECT tracers. In contrast to SPECT, PET offers a higher spatial resolution and, owing to the Ge/Ga generator, an analog to the established Tc generator exists. Complexation of Ga(III) requires the use of chelators. Therefore, DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), NOTA (1,4,7-triazacyclododecane-1,4,7-triacetic acid), and their derivatives, are often used. The combination of these macrocyclic chelators and bisphosphonates is currently studied worldwide. The use of DOTA offers the possibility of a therapeutic application by complexing the β-emitter Lu. This overview describes the possibility of diagnosing bone metastases using [Ga]Ga-BPAMD (Ga-labeled (4-{[bis-(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl)acetic acid) as well as the successful application of [Lu]Lu-BPAMD for therapy and the development of new diagnostic and therapeutic tools based on this structure. Improvements concerning both the chelator and the bisphosphonate structure are illustrated providing new Ga- and Lu-labeled bisphosphonates offering improved pharmacological properties.
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http://dx.doi.org/10.3390/ph10020045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490402PMC
May 2017

Surgery in Focal Congenital Hyperinsulinism (CHI) - The "Hyperinsulinism Germany International" Experience in 30 Children.

Pediatr Endocrinol Rev 2016 Dec;14(2):129-137

Otto-von-Guericke-University, Pediatrics, Magdeburg, Germany.

Objectives: Results of surgery for focal CHI in 30 children PATIENTS AND METHODS: All showed an ABCC8 or KCNJ11 mutation. After PET/CT in 29 children and PET/MRT in 1 case, frozen-section guided resection was performed, in left-sided cases by laparoscopy. Mean age at surgery was 11.7 months (2-49).

Results: In 28/30 children, the PET/CT or MRT correlated with histopathology. In two cases, a focal lesion was undectable; one of these was cured, one not. In total, 24 children showed lesions with sizes of 5-12 mm. All were cured instantly. In four children with huge lesions in the pancreatic head, pathological cells remained at the resection margins. One child was cured instantly, two children after a 2nd surgery, and one child was not cured, even after three surgeries. The overall cure rate was 93%.

Conclusions: Imaging, surgical findings, histopathology and clinical outcome in surgery for focal CHI match in most, but not all cases.
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http://dx.doi.org/10.17458/PER.2016.BVE.SurgeryinfocalDOI Listing
December 2016

Occurrence of giant focal forms of congenital hyperinsulinism with incorrect visualization by (18) F DOPA-PET/CT scanning.

Clin Endocrinol (Oxf) 2014 Dec 19;81(6):847-54. Epub 2014 May 19.

Institut für experimentelle pädiatrische Endokrinologie, Charité Universitätsmedizin, Berlin, Germany.

Context: Congenital hyperinsulinism (CHI) is a rare disease characterized by severe hypoglycaemic episodes due to pathologically increased insulin secretion from the pancreatic beta cells. When untreated, CHI might result in irreversible brain damage and death. Currently, two major subtypes of CHI are known: a focal form, associated with local distribution of affected beta cells and a nonfocal form, affecting every single beta cell. The identification of focal forms is important, as the patients can be cured by limited surgery. (18) F DOPA-PET/CT is an established non-invasive approach to differentiate focal from nonfocal CHI.

Objective: The purpose of this study was to identify possible limitations of (18) F DOPA-PET/CT scan in patients with focal forms nonfocal CHI.

Design: A retrospective chart review of 32 patients (from 2008 through 2013) who underwent (18) F DOPA-PET/CT and partial pancreatectomy for focal CHI at the reference centres in Berlin, Germany and London, UK.

Results: In most cases (n = 29, 90·7%), (18) F DOPA-PET/CT was sufficient to localize the complete focal lesion. However, in some patients (n = 3, 9·3%), (18) F DOPA-PET/CT wrongly visualized only a small portion of the focal lesion. In this group of patients, a so-called 'giant focus' was detected in histopathological analysis during the surgery.

Conclusions: Our data show that in most patients with focal CHI (18) F DOPA-PET/CT correctly predicts the size and anatomical localisation of the lesion. However, in those patients with a 'giant focal' lesion (18) F DOPA-PET/CT is unreliable for correct identification of 'giant focus' cases.
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http://dx.doi.org/10.1111/cen.12473DOI Listing
December 2014

Clinical and genetic evaluation of patients with KATP channel mutations from the German registry for congenital hyperinsulinism.

Horm Res Paediatr 2014 7;81(3):156-68. Epub 2014 Jan 7.

Department of Pediatrics, Otto von Guericke University Magdeburg, Magdeburg, Germany.

Congenital hyperinsulinism (CHI) causes hypoglycemia due to irregular insulin secretion. In infants, a rapid diagnosis and appropriate management to avoid severe hypoglycemia is mandatory. CHI is a heterogeneous condition at the clinical and genetic level, and disease-causing genes have been identified in about half of the patients. The majority of mutations have been identified in the ABCC8 and KCNJ11 genes encoding subunits of the KATP channel responsible for two distinct histological forms. The diffuse form is caused by autosomal recessive or dominant inherited mutations, whereas the focal form is caused by a paternally transmitted recessive mutation and a second somatic event. We report on an unselected cohort of 136 unrelated patients from the German CHI registry. Mutations in either the ABCC8 or KCNJ11 gene were identified in 61 of these patients (45%). In total, 64 different mutations including 38 novel ones were detected in this cohort. We observed biparental (recessive) inheritance in 34% of mutation-positive patients, dominant inheritance in 11% and paternal transmission of a mutation associated with a focal CHI type in 38%. In addition, we observed inheritance patterns that do not exactly follow the classical recessive or dominant mode, further adding to the genetic complexity of this disease.
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http://dx.doi.org/10.1159/000356905DOI Listing
December 2014

Techniques in pediatric surgery: congenital hyperinsulinism.

Horm Res Paediatr 2011 16;75(4):304-10. Epub 2011 Feb 16.

Clinic for Pediatric Surgery, University Greifswald, Greifswald, Germany.

For surgery in congenital hyperinsulinism (CHI), a distinct surgical strategy and technique is required for focal, diffuse and atypical CHI. In focal CHI, a confined, localized and parenchyma-sparing resection which is guided by the PET-CT is always indicated in order to cure the patient. In diffuse CHI, however, the results of surgical therapy are unpredictable and cure is an exception. Therefore, a strong tendency exists nowadays that medical therapy should be preferred in diffuse CHI. In atypical CHI the situation is more complex: if the focal lesion or the segmental mosaic are not too extensive, cure by resection should be possible. But care must be taken in atypical cases not to resect too much of the gland in order not to induce diabetes.
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http://dx.doi.org/10.1159/000323532DOI Listing
July 2011

Visualization of the focus in congenital hyperinsulinism by intraoperative sonography.

Semin Pediatr Surg 2011 Feb;20(1):28-31

Pediatric Radiology, O. v. Guericke University, Magdeburg, Germany.

In surgery for focal congenital hyperinsulinism (CHI), the identification and complete resection of the focus without collateral damage is of utmost importance. In a pilot study we applied intra-abdominal high-frequency sonography during surgery for focal CHI in 2 infants. The focus could be identified, its relation to the pancreatic and common bile duct could be shown, and the typical octopus-like tentacles could be demonstrated. In one case the resection was successful; in the other it was not. These preliminary results suggest that intraoperative sonography could be a valuable tool in the surgical therapy of focal CHI and warrants further evaluation in a clinical study.
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http://dx.doi.org/10.1053/j.sempedsurg.2010.10.011DOI Listing
February 2011

Positron emission tomography/computed tomography diagnostics by means of fluorine-18-L-dihydroxyphenylalanine in congenital hyperinsulinism.

Semin Pediatr Surg 2011 Feb;20(1):23-7

Diagnostisch Therapeutisches Zentrum, Kadinerstrasse, Berlin, Germany.

The unfavorable prognosis of congenital hyperinsulinism (CHI) can be avoided if the patients are treated with high-dose glucose infusions and timely surgical intervention. Circumscribed foci used to be identified by selective percutaneous pancreatic vein catheterization and determination of the insulin level. Fluorine-18-L-dihydroxyphenylalanine-positron emission tomography (PET) was developed as a milder alternative for diagnostic localization of focal disease. The uptake of fluorine-18-L-dihydroxyphenylalanine is considerably increased in foci with high insulin synthesis rates. In Berlin, diagnosis was achieved by high definition PET/computed tomography with multiphase contrast media protocols that provided all necessary data with one investigation. We have investigated 135 patients with congenital hyperinsulinism, including 45 patients with focal disease (33.3%). All the foci were excised on the basis of PET/computed tomography images. The German data demonstrate that 87% to 91% of the operated patients could be completely healed.
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http://dx.doi.org/10.1053/j.sempedsurg.2010.10.007DOI Listing
February 2011

Techniques in pediatric surgery: congenital hyperinsulinism.

Horm Res Paediatr 2010 24;74(6):438-43. Epub 2010 Nov 24.

Clinic for Pediatric Surgery, University Greifswald, Greifswald, Germany. winfried.barthlen @ uni-greifswald.de

For surgery in congenital hyperinsulinism (CHI), a distinct strategy and technique is required for focal, diffuse and atypical types. In focal CHI, a confined, localized and parenchyma-sparing resection which is guided by the PET-CT is always indicated in order to cure the patient. In diffuse CHI, however, the results of surgical therapy are unpredictable and cure is an exception. Therefore, a strong tendency exists nowadays that medical therapy should be preferred in diffuse CHI. In atypical CHI the situation is more complex: if the focal lesion or the segmental mosaic are not too extensive, cure by resection should be possible. But care must be taken in atypical cases not to resect too much of the gland in order not to induce diabetes.
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http://dx.doi.org/10.1159/000321902DOI Listing
April 2011

Evaluation of [18F]fluoro-L-DOPA positron emission tomography-computed tomography for surgery in focal congenital hyperinsulinism.

J Clin Endocrinol Metab 2008 Mar 11;93(3):869-75. Epub 2007 Dec 11.

Clinic for Pediatric Surgery, Institute for Pathology, Charité University Medicine Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, Mittelallee 8, D-13353 Berlin, Germany.

Context: In congenital hyperinsulinism (CHI), the identification and precise localization of a focal lesion is essential for successful surgery.

Objective: Our objective was to evaluate the predictive value and accuracy of integrated [18F]fluoro-L-DOPA ([18F]FDOPA) positron emission tomography (PET)-computed tomography (CT) for the surgical therapy of CHI.

Design: This was an observational study.

Setting: The study was performed in the Department of Pediatric Surgery at a university hospital.

Patients: From February 2005 to September 2007, 10 children with the clinical signs of CHI and an increased radiotracer uptake in a circumscribed area of the pancreas in the [18F]FDOPA PET-CT were evaluated.

Interventions: Guided by the [18F]FDOPA PET-CT report, all children underwent partial pancreatic resection, in two cases twice.

Main Outcome Measures: Correlation of the anatomical findings at surgery with the report of the [18F]FDOPA PET-CT, and the results of surgery and clinical outcome were determined.

Results: In nine children the intraoperative situation corresponded exactly to the description of the [18F]FDOPA PET-CT. A limited resection of the pancreas was curative in eight cases at the first surgery, in one case at the second intervention. We observed no diabetes mellitus or exocrine insufficiency in the follow up so far. In one child, hypoglycemia persisted even after two partial resections of the pancreatic head. Histological analysis finally revealed an atypical intermediate form of CHI.

Conclusions: The integrated [18F]FDOPA PET-CT is accurate to localize the lesion in focal CHI and is a valuable tool to guide the surgeon in limited pancreatic resection.
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http://dx.doi.org/10.1210/jc.2007-2036DOI Listing
March 2008