Search PubMed⌕ Search

Biomedical subjects

A Otte

Publications and source records attributed to A Otte.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Yttrium 90 DOTATOC: a new somatostatin analog for cancer therapy of neuroendocrine tumors].

Current concepts for the treatment of somatostatin receptor positive tumours have not been very motivating up to now. A promising alternative could be the new peptidic vector DOTA-D-Phe1-Tyr3-Octreotide (DOTATOC) recently developed in Basel. It may be labelled with the beta-emitter yttrium-90 (90Y) for internal radiotherapy after systemic application. Pilot therapy studies have shown convincing results with this new radiopharmaceutical. These studies are presented with regard to efficacy and possible toxicity. In summary, the new receptor-mediated 90Y-DOTATOC therapy led to tumour response in the majority of patients, and only in some receiving high cumulative doses of > 200 mCi per m2 body surface renal and hematological toxicity due to irradiation occurred. For the reduction of renal accretion, concepts with concomitant amino acid infusions containing L-lysine in a higher concentration are currently under way.

Female↗
PubMed1999

Locoregional regulatory peptide receptor targeting with the diffusible somatostatin analogue 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC): a pilot study in human gliomas.

Human gliomas, especially of low-grade type, have been shown to express high-affinity somatostatin receptor type 2 (J-C. Reubi et al., Am. J. Pathol, 134: 337-344, 1989). We enrolled seven low-grade and four anaplastic glioma patients in a pilot study using the diffusible peptidic vector 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC) for receptor targeting. The radiopharmakon was locoregionally injected into a stereotactically inserted Port-a-cath. DOTATOC competes specifically with somatostatin binding to somatostatin receptor type 2 in the low nanomolar range as shown by a displacement curve of 125I-[Tyr3]-octreotide in tumor tissue sections. Diagnostic (111)In-labeled DOTATOC-scintigraphy following local injection displayed homogeneous to nodular intratumoral vector distribution. The cumulative activity of regionally injected peptide-bound 90Y amounted to 370-3300 MBq, which is equivalent to an effective dose range between 60 +/- 15 and 550 +/- 110 Gy. Activity was injected in one to four fractions according to tumor volumes; 1110 MBq of 90Y-labeled DOTATOC was the maximum activity per single injection. We obtained six disease stabilizations and shrinking of a cystic low-grade astrocytoma component. The only toxicity observed was secondary perifocal edema. The activity:dose ratio (MBq:Gy) represents a measure for the stability of peptide retention in receptor-positive tissue and might predict the clinical course. We conclude that SR-positive human gliomas, especially of low-grade type, can be successfully targeted by intratumoral injection of the metabolically stable small regulatory peptide DOTATOC.

Adult↗
PubMed1999

Yttrium-90 DOTATOC: first clinical results.

In a pilot study, DOTA-d-Phe(1)-Tyr(3)-octreotide (DOTATOC), which can be labelled with the beta-emitting radioisotope yttrium-90, has recently been used for the treatment of patients with advanced somatostatin receptor-positive tumours who had no other treatment option. The aim of the present study was to elucidate the therapeutic potential of (90)Y-DOTATOC in a larger number of patients employing a standardized treatment protocol. Careful attention was paid to any side-effects (renal and/or haematological toxicity). Of 44 patients with advanced somatostatin receptor-positive tumours of different histology, 29 could be included in the study. The 15 patients who were excluded from the study protocol were assigned to our institution for purely compassionate reasons. The 29 patients who were included received four or more single doses of (90)Y-DOTATOC with ascending activity at intervals of approximately 6 weeks (cumulative dose 6120+/-1347 MBq/m(2)) with the aim of performing an intra-patient dose escalation study. In total, 127 single treatments were given. In eight of these 127 single treatments, total doses of > or = 3700 MBq were administered. In an effort to prevent renal toxicity, two patients received Hartmann-Hepa 8% solution during all therapy cycles, while 13 patients did so during some but not all therapy cycles; in 14 patients no solution was administered during the therapy cycles. The treatment was monitored by computed tomography and indium-111 DOTATOC scintigraphy. Blood parameters were controlled weekly, while tumour markers and liver enzymes were controlled 6-weekly. Of the 29 patients, 24 patients showed no severe renal or haematological toxicity (toxicity < or = grade 2 according to the National Cancer Institute grading criteria). These 24 patients received a cumulative dose of < or = 7400 MBq/m(2). Five patients developed renal and/or haematological toxicity. All of these five patients received a cumulative dose of >7400 MBq/m(2) and had received no Hartmann-Hepa 8% solution during the therapy cycles. Four of the five patients developed renal toxicity; two of these patients showed stable renal insufficiency and two require haemodialysis. Two of the five patients exhibited anaemia (both grade 3) and thrombopenia (grade 2 and 4, respectively). To date, 20 of the 29 patients have shown a disease stabilization, two a partial remission, four a reduction of tumour mass <50% and three a progression of tumour growth. (90)Y-DOTATOC could be a powerful and promising new therapeutic agent for anti-cancer treatment - at least in terms of an adjuvant starting point of the disease. However, problems with toxicity have to be solved. Evaluation of the effect of amino acid infusions (e.g. Hartmann-Hepa 8% solution) during (90)Y-DOTATOC treatments with the aim of reducing renal toxicity is ongoing.

Adult↗
PubMed1999

[Marine-Lenhart syndrome: a case observation upon 18 years].

After a hyperthyroidism of Graves' disease with strongly positive antithyroid antibodies treated sufficiently by radioiodine therapy a 46-year old woman developed a consecutive bifocal autonomous nodule within 13 years. This phenomenon is known as Marine-Lenhart-syndrome. In this particular case it seems that autonomous nodules are a consequence of Graves' disease treatment with radioiodine. Our case report is a 18 year follow up. In contrast to most studies known today the simultaneous occurrence of active Graves' disease and active autonomous nodules could be demonstrated by means of serology and suppressive scintigraphy, respectively. In addition, this case shows the possible dependence of an acute beginning of Graves' disease and the occurrence of autonomous nodules.

Female↗
PubMed1998

Crossed cerebellar diaschisis and brain tumor biochemistry studied with positron emission tomography, [18F]fluorodeoxyglucose and [11C]methionine.

Cerebral gliomas may cause a reduction of glucose metabolism in the cerebellum contralateral to the tumor side (crossed cerebellar diaschisis, CCD). We investigated whether CCD is related to tumor localization, histological grade, size and tumor biochemistry. Cerebellar glucose metabolism was measured in 44 glioma patients and 15 healthy subjects using positron emission tomography and [18F]fluorodeoxyglucose (FDG). CCD was determined by calculating an asymmetry index of cerebellar glucose metabolism. Further, the tumor uptake of FDG and [11C]methionine (MET) was also assessed, and was expressed as ratio of normalized tracer uptake in tumor over contralateral cortex (T/C). Frontal lobe tumors were associated with highest CCD values. For these tumors, CCD was higher in malignant (-11.8+/-9.9%) than in low-grade (-4.3+/-4.1%) gliomas (P=0.010). In addition, frontal lobe tumors showed increasing CCD values with increasing size. In tumors of the parietal or temporal lobe, CCD was less marked or absent. T/C ratios of tumor tracer uptake were higher in malignant than in low-grade gliomas, but were not correlated with CCD. Our data indicate that the magnitude of CCD is mainly determined by tumor localization and size, the latter being associated with tumor grade. These findings raise the question whether CCD provides a measure of expansion or progression particularly in low-grade tumors of the frontal lobe.

Adult↗
PubMed1998

Combined FDG and [F-18]fluoride whole-body PET: a feasible two-in-one approach to cancer imaging?

PURPOSE: To evaluate the diagnostic usefulness of the combined application of 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG; for the evaluation of soft tissue) and [F-18]fluoride (for the evaluation of the skeleton) in positron emission tomography (PET) of cancer. MATERIALS AND METHODS: Sixty consecutive patients (23 women, 37 men; mean age +/- SD, 51 years +/- 14; age range, 13-76 years) were entered into this prospective study. Thirty patients underwent only FDG PET. Thirty patients underwent combined FDG and fluoride PET. The PET findings were correlated with the findings of other imaging modalities. Interobserver agreement for the anatomic lesion localization was calculated with the use of the kappa statistic. RESULTS: All 30 combined FDG and fluoride studies yielded high-quality whole-body images. PET findings correlated with other imaging findings in 54 (78%) of 69 lesions in the control group and with 64 (88%) of 73 lesions in the combined group. Interobserver agreement in the control group was 0.74; it was 0.95 in the combined group. CONCLUSION: Combined FDG and fluoride PET is an advanced metabolic imaging approach for the evaluation of cancer.

Adolescent↗
PubMed1998

Neuropsychiatric systemic lupus erythematosus before and after immunosuppressive treatment: a FDG PET study.

At its inception, morphological imaging, like magnetic resonance imaging (MRI), is often not useful in neuropsychiatric systemic lupus erythematosus (NPSLE), although the disease clinically shows cerebral symptoms. Functional imaging, like positron emission tomography (PET), may be a method that offers some advantages. We report a 53-year-old white man with decreased memory and visual disturbances who met four of the American Rheumatism Association (ARA) criteria for the classification of SLE. He was investigated before and after 3 months of therapy using PET and F-18-fluoro-2-deoxy-D-glucose (FDG). Treatment consisted of prednisone (25 mg/day, tapered to 10 mg/day) and cyclophosphamide (daily 100 mg for 3 weeks followed by a drug-free interval of 1 week). For the control group, 15 clinically and neurologically healthy volunteers (5 male, 10 female, aged 48 +/- 7 years) were investigated. All study participants additionally had a cranial MRI. In both controls and the SLE patient, cranial MRI was negative. However, the patient showed a significant hypometabolism in the region parieto-occipital on both sides and the parietal region on the right side before treatment. After treatment metabolism in these regions was within normal limits. Hence, FDG-PET could help to verify brain-onset of SLE earlier and may be a powerful tool for controlling SLE treatment.

Adult↗
PubMed1997

Identification of Bmi1-interacting proteins as constituents of a multimeric mammalian polycomb complex.

The Bmi1 gene has been identified as a mouse Polycomb group (Pc-G) gene implicated in the regulation of Hox gene expression. Here we describe the characterization of a Bmi binding protein Mph1, which shares similarity to Drosophila polyhomeotic. Coimmunoprecipitation experiments indicate that Bmi1 and Mph1, as well as the Mel18 and M33 proteins described previously, are constituents of a multimeric protein complex in mouse embryos and human cells. A central domain of Bmi1 interacts with the carboxyl terminus of Mph1, whereas a conserved alpha-helical domain in the Mph1 protein is required for its homodimerization. Transgenic mice overexpressing various mutant Bmi1 proteins demonstrate that the central domain of Bmil is required for the induction of anterior transformations of the axial skeleton. Bmi1, M33, and Mph1 show an overlapping speckled distribution in interphase nuclei. These data provide molecular evidence for the existence of a mammalian Polycomb complex.

Amino Acid Sequence↗
PubMed1997

Brain glucose utilization in systemic lupus erythematosus with neuropsychiatric symptoms: a controlled positron emission tomography study.

In contrast to morphological imaging [such as magnetic resonance imaging (MRI) or computed tomography], functional imaging may be of advantage in the detection of brain abnormalities in cases of neuropsychiatric systemic lupus erythematosus (SLE). Therefore, we studied 13 patients (aged 40+/-14 years, 11 female, 2 male) with neuropsychiatric SLE who met four of the American Rheumatism Association criteria for the classification of SLE. Ten clinically and neurologically healthy volunteers served as controls (aged 40+/-12 years, 5 female, 5 male). Both groups were investigated using fluorine-18-labelled fluorodeoxyglucose brain positron emission tomography (PET) and cranial MRI. The normal controls and 11 of the 13 patients showed normal MRI scans. However, PET scan was abnormal in all 13 SLE patients. Significant group-to-group differences in the glucose metabolic index (GMI=region of interest uptake/global uptake at the level of the basal ganglia and thalamus) were found in the parieto-occipital region on both sides: the GMI of the parieto-occipital region on the right side was 0.922+/-0.045 in patients and 1.066+/-0.081 in controls (P<<0.0001, Mann Whitney U test), while on the left side it was 0.892+/-0.060 in patients and 1. 034+/-0.051 in controls (P=0.0002). Parieto-occipital hypometabolism is a conspicuous finding in mainly MRI-negative neuropsychiatric SLE. As the parieto-occipital region is located at the boundary of blood supply of all three major arteries, it could be the most vulnerable zone of the cerebrum and may be affected at an early stage of the cerebrovascular disease.

Adult↗
PubMed1997

DOTATOC: a powerful new tool for receptor-mediated radionuclide therapy.

This study presents the first successful use of a peptidic vector, DOTATOC, labelled with the beta-emitting radioisotope yttrium-90, for the treatment of a patient with somatostatin receptor-positive abdominal metastases of a neuroendocrine carcinoma of unknown localization. Tumour response and symptomatic relief were achieved. In addition, the new substance DOTATOC was labelled with the diagnostic chemical analogue indium-111 and studied in three patients with histopathologically verified neuroendocrine abdominal tumours for its diagnostic sensitivity and compared with the commercially available OctreoScan. In all patients the kidney-to-tumour uptake ratio (in counts per pixel) was on average 1. 9-fold lower with 111In-DOTATOC than with OctreoScan. DOTATOC could be a potential new diagnostic and therapeutic agent in the management of neuroendocrine tumours.

Abdominal Neoplasms↗
PubMed1997

[Indications for nuclear medicine diagnosis in trauma surgery].

Skeletal scintigraphy is the most frequently utilized nuclear medicine imaging procedure in traumatology. Concerning any skeletal abnormality associated with changes in local perfusion, exudation and metabolism, it is a sensitive functional imaging procedure to detect bony disease. However, because of the varying causes of bony disease, it is characterized by a low specificity. Further, specificity may be enhanced, when patient history, clinical and lab results as well as results obtained from other diagnostic imaging procedures are combined with the result of skeletal scintigraphy. On the other hand, it is known that metabolic abnormalities of the skeleton depicted by radionuclide imaging occur much earlier than structural changes visible on X-ray imaging. Beside skeletal scintigraphy, antigranulocyte antibody or labelled leucocyte imaging may greatly assist in the detection of inflammation or infection following joint replacement surgery, respectively. Ultimatively, a combination of clinical, lab and imaging results including radionuclide imaging may represent the best approach to answer some questions asked by surgical traumatologists.

Bone and Bones↗
PubMed1997

Incidental appendix carcinoid. Value of somatostatin receptor imaging.

PURPOSE: Somatostatin receptor scintigraphy is used to diagnose carcinoid of the gastrointestinal tract. Its sensitivity ranges from approximately 75%-100%. Therefore, it was hypothesized that it can be used in the postsurgical follow-up to detect residual carcinoid, recurrence, and metastatic disease. RESULTS: This article is concerned with the findings of somatostatin receptor imaging performed on a 12-year-old girl 8 weeks after appendectomy. Histologic examination showed an incidental appendix carcinoid. Somatostatin receptor scintigraphy performed for detection of lymph node metastatic spread of the carcinoid showed focal tracer accumulation at the former operative site; subsequently, a right hemicolectomy was performed. However, histologic examination of the surgical tissue showed no evidence for carcinoid. CONCLUSION: It is concluded that there are some potential pitfalls for somatostatin receptor imaging at least soon after surgery. Therefore, it should not be used to aid in reoperation.

Appendiceal Neoplasms↗