111In-pentetreotide scintigraphy: procedure guidelines for tumour imaging.

This document provides general information about somatostatin receptor scintigraphy with (111)In-pentetreotide. This guideline should not be regarded as the only approach to visualise tumours expressing somatostatin receptors or as exclusive of other nuclear medicine procedures useful to obtain comparable results. The aim of this guideline is to assist nuclear medicine physicians in recommending, performing, reporting and interpreting the results of (111)In-pentetreotide scintigraphy.

Highly improved metabolic stability and pharmacokinetics of indium-111-DOTA-gastrin conjugates for targeting of the gastrin receptor

The development of metabolically stable radiolabeled gastrin analogues with suitable pharmacokinetics is a topic of recent research activity. These imaging vectors are of interest because the gastrin/CCK2 receptor is highly overexpressed in different tumors such as medullary thyroid cancer, neuroendocrine tumors, and SCLC. The drawback of current targeting agents is either their metabolic instability or their high kidney uptake. We present the synthesis and in vitro and in vivo evaluation of 11 (111)In-labeled DOTA-conjugated peptides that differ by their spacer between the peptide and the chelate. We introduced uncharged but hydrophilic spacers such as oligoethyleneglycol, serine, and glutamine. The affinity of all radiopeptides was high with IC(50) values between 0.5 and 4.8 nM. The improvement of human serum stability is 500-fold within this series of compounds. In addition the kidney uptake could be lowered distinctly and the tumor-to-kidney ratio improved almost 60-fold if compared with radiotracers having charged spacers such as glutamic acid.

A rare case of a large spinal meningioma with mediastinal extension and malignant behavior classified histologically as benign

AIM To report a rare case of a spinal WHO grade I meningioma extending through intervertebral foramina C7 to D4 with an extensive mediastinal mass and infiltration of the vertebrae, and to discuss the malignant behavior of a tumor classified as benign. METHODS (Clinical Presentation, Histology, and Imaging): A 54-year-old man suffered from increasing lower back pain with gait difficulties, weakness and numbness of the lower extremities, as well as urge incontinence. CT scan of the thorax and MRI scan of the spine revealed a large prevertebral tumor, which extended to the spinal canal and caused compression of the spinal cord at the levels of C7 to D4 leading to myelopathy with hyperintense signal alteration on T2-weighted MRI images. The signal constellation (T1 with and without contrast, T2, TIR) was highly suspicious for infiltration of vertebrae C7 to D5. Somatostatin receptor SPECT/CT with (111)In-DTPA-D: -Phe-1-octreotide detected a somatostatin receptor-positive mediastinal tumor with infiltration of multiple vertebrae, dura, and intervertebral foramina C7-D4, partially with Krenning score >2. Percutaneous biopsies of the mediastinal mass led to histopathological findings of WHO grade I meningioma of meningothelial subtype. RESULTS (Therapy): C7 to D4 laminoplasty was performed, and the intraspinal, extradural part of the tumor was microsurgically removed. Postoperative stereotactic radiation therapy was done using the volumetric modulated arc therapy (VMAT) technique (RapidArc). No PRRNT with (90)Y-DOTA-TOC was done. CONCLUSIONS Due to the rare incidence and complex presentation of this disease not amenable to complete surgical resection, an individualized treatment approach should be worked out interdisciplinarily. The treatment approach should be based not only on histology but also on clinical and imaging findings. Close clinical and radiological follow-up may be mandatory even for benign tumors.

Differential uptake of (68)Ga-DOTATOC and (68)Ga-DOTATATE in PET/CT of gastroenteropancreatic neuroendocrine tumors

PURPOSE Abundant expression of somatostatin receptors (sst) is a characteristic of neuroendocrine tumors (NET). Thus, radiolabeled somatostatin analogs have emerged as important tools for both in vivo diagnosis and therapy of NET. The two compounds most often used in functional imaging with positron emission tomography (PET) are (68)Ga-DOTATATE and (68)Ga-DOTATOC. Both analogs share a quite similar sst binding profile. However, the in vitro affinity of (68)Ga-DOTATATE in binding the sst subtype 2 (sst2) is approximately tenfold higher than that of (68)Ga-DOTATOC. This difference may affect their efficiency in detection of NET lesions, as sst2 is the predominant receptor subtype on gastroenteropancreatic NET. We thus compared the diagnostic value of PET/CT with both radiolabeled somatostatin analogs ((68)Ga-DOTATATE and (68)Ga-DOTATOC) in the same patients with gastroenteropancreatic NET. PATIENTS AND METHODS Twenty-seven patients with metastatic gastroenteropancreatic NET underwent (68)Ga-DOTATOC and (68)Ga-DOTATATE PET/CT as part of the workup before prospective peptide receptor radionuclide therapy (PRRT). The performance of both imaging methods was analyzed and compared for detection of individual lesions per patient and for eight defined body regions. A region was regarded as positive if at least one lesion was detected in that region. In addition, radiopeptide uptake in terms of the maximal standardized uptake value (SUV(max)) was compared for concordant lesions and renal parenchyma. RESULTS Fifty-one regions were found positive with both (68)Ga-DOTATATE and (68)Ga-DOTATOC. Overall, however, significantly fewer lesions were detected with (68)Ga-DOTATATE in comparison with (68)Ga-DOTATOC (174 versus 179, p < 0.05). Mean (68)Ga-DOTATATE SUV(max) across all lesions was significantly lower compared with (68)Ga-DOTATOC (16.9 ± 6.8 versus 22.1 ± 12.0, p < 0.01). Mean SUV(max) for renal parenchyma was not significantly different between (68)Ga-DOTATATE and (68)Ga-DOTATOC (12.6 ± 2.6 versus 12.6 ± 2.7). CONCLUSIONS (68)Ga-DOTATOC and (68)Ga-DOTATATE possess similar diagnostic accuracy for detection of gastroenteropancreatic NET lesions (with a potential advantage of (68)Ga-DOTATOC) despite their evident difference in affinity for sst2. Quite unexpectedly, maximal uptake of (68)Ga-DOTATOC tended to be higher than its (68)Ga-DOTATATE counterpart. However, tumor uptake shows high inter- and intraindividual variance with unpredictable preference of one radiopeptide. Thus, our data encourage the application of different sst ligands to enable personalized imaging and therapy of gastroenteropancreatic NET with optimal targeting of tumor receptors.

Lääkintäneuvos Rikke (Richard) Sotamaa 9/4 1973

Kirje 9.4.1973

Na 1 Nachlass Max Horkheimer, 4 - Korrespondenzen u.a. mit Richard Bach (p. I 2, 131-358)

24 Briefe zwischen Richard Bach und Max Horkheimer, 1938-1940; 2 Briefe zwischen Alfred Chalk und Max Horkheimer, 17.10.1939, 14.11.1939; 3 Briefe von Morduch Lexandrowitsch und der American Consulate General, 1939; 4 Briefe von der American Consulate General und Max Horkheimer, 1938-1939; 1 Brief von Max Horkheimer an das Amtstgericht Berlin, 15.03.1939; 1 Brief von Max Horkheimer an Stiedry, 05.12.1938; 1 Brief von Max Horkheimer an den Collector of Custom, 26.10.1938; 2 Briefe zwischen Josef Maier und Carson Alexandrowitsch, 28.06.1938, 29.06.1938; 1 Brief von Margarete Baruch an Alice Maier, 11.04.1938; 1 Brief von Emanuel List an Carson Alexandrowitsch, 23.02.1938; 1 Abschrift des Briefes von der Metropolitan Opera Association New York an Morduch Lexandrowitsch, 22.02.1938; 1 Brief von Jacques Barzun an Max Horkheimer, 09.07.1947; 4 Briefe zwischen K. Baschwitz und Max Horkheimer, 1938-1946; 2 Briefe zwischen E. Bauer und Max Horkheimer, 08.04.1935, 27.05.1935; 4 Briefe zwischen Fritz Bauer und Max Horkheimer, 1937-1938; 2 Briefe zwischen Lina Bauer und Max Horkheimer, 20.07.1942, 16,08,1942; 4 Briefe zwsichen Rudolf Bauer und Max Horkheimer, 1937; 15 Briefe zwischen Gertrud Bauer und Max Horkheimer, 1938-1941; 1 Brief von Max Horkheimer an den Collector of Customs, 15.03.1940; 2 Briefe zwischen I. Hannah Davidson vom Jewish Community Center San Francisco und Max Horkheimer, 19.09.1938, 29.09.1938; 2 Briefe zwsichen I. Bauer und Max Horkheimer, 25.09.1938, 29.09.1938; 1 Brief von Max Horkheimer an Klopfer, 27.09.1938; 3 Briefe zwischen Y.M.H.A. - Y.W.H.A The Jewish Center of Saint Louis und Max Horkheimer, 19.09.1938, 1938; 1 Brief von Max Horkheimer an Julius Rosenberg, 17.09.1938; 1 Brief von Max Horkheimer an das Jwish Center Salt Lake City, Utah, 07.09.1938; 1 Brief von Max Horkheimer an das Jewish Community Center San Fransisco, 07.09.1938; 3 Briefe zwischen dem New York Section of the National Council of Jewish Women und Max Horkheimer, 07.04.1938, 1938; 2 Briefe zwischen Baum und Max Horkheimer, 12.03.1946, 25.05.1946; 1 Brief von Max Horkheimer an Charles A. Beard , 12.12.1934; 1 Brief von Charles A. Beard an C. A. Beard; 5 Briefe von Friedrich Pollock an Charles A. Beard, 1940-1941; 5 Briefe zwischen Lilo Beck und Max Horkheimer, 1940-1941; 7 Briefe zwischen Maximilian Beck und Max Horkheimer, 1939-1940; 1 Brief von Paul Tillich an Max Horkheimer , 01.10.1940; 1 Brief von dem Emergency Committee in Aid of Displaced Foreign Scholars New York an Max Horkheimer, 19.04.1940; 5 Briefe zwischen Konrad Bekker und Max Horkheimer, 1936-1939; 2 Briefe von Max Horkheimer an Ludwig Bendix, 1921, 1937; 1 Brief von Peter Bendmann an Max Horkheimer; 1 Brief von Max Horkheimer an Ruth Benedict, 30.07.1937; 1 Brief von Eric Russel Bentley an Max Horkheimer, 30.01.1945; 1 Brief von George Berg an Max Horkheimer, 12.07.1945; 2 Briefe zwischen Egon Bergel und Max Horkheimer, 18.08.1938, 22.08.1938; 1 Brief von Marie Jahoda an Max Horkheimer, 14.07.1928; 1 Brief von Theodor W. Adorno an Kurt Bergel, 09.09.1939; 15 Briefe zwischen Klaus Berger und Max Horkheimer, 1936-1943; 1 Brief von Frederick Pollock an Philip M. Hayden von der Columbia University New York, 05.03.1942; 1 Brief von Hans Venedey an Max Horkheimer, 05.03.1938; 1 Brief von Max Horkheimer an Ida Berger-Chevant, 18.02.1939;

Repeated blood pressure measurements in a sample of Swedish twins: heritabilities and associations with polymorphisms in the renin-angiotensin-aldosterone system Iliadou, Anastasia, Lichtenstein, Paul, Morgenstern, Ralf, Forsberg, Lena, Svensson, Richard, de Faire, Ulf, Martin, Nicholas, Pedersen, Nancy

Background Twin and family studies have shown that genetic effects explain a relatively high amount of the phenotypic variation in blood pressure. However, many studies have not been able to replicate findings of association between specific polymorphisms and diastolic and systolic blood pressure. Methods In a structural equation-modelling framework the authors investigated longitudinal changes in repeated measures of blood pressures in a sample of 298 like-sexed twin pairs from the population-based Swedish Twin Registry. Also examined was the association between blood pressure and polymorphisms in the angiotensin-I converting enzyme and the angiotensin 11 receptor type 1 with the 'Fulker' test Both linkage and association were tested simultaneously revealing whether the polymorphism is a Quantitative Trait Locus (QTL) or in linkage disequilibrium with the QTL. Results Genetic influences explained up to 46% of the phenotypic variance in diastolic and 63% of the phenotypic variance in systolic blood pressure. Genetic influences were stable over time and contributed up to 78% of the phenotypic correlation in both diastolic and systolic blood pressure. Non-shared environmental effects were characterised by time specific influences and little transmission from one time point to the next. There was no significant linkage and association between the polymorphisms and blood pressure. Conclusions There is a considerable genetic stability in both diastolic and systolic blood pressure for a 6-year period of time in adult life. Non-shared environmental influences have a small long-term effect Although associations with the polymorphisms could not be replicated, results should be interpreted with caution due to power considerations. (C) 2002 Lippincott Williams Wilkins.