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Biomedical subjects

M Friebe

Publications and source records attributed to M Friebe.

10 recordsLinked to original sources
PubMed2001

[99mTc]oxotechnetium(V) complexes amine-amide-dithiol chelates with dialkylaminoalkyl substituents as potential diagnostic probes for malignant melanoma.

[99mTc]oxotechnetium(V) complexes of amine-amide-dithiol (AADT) chelates containing tertiary amine substituents were synthesized and shown to have affinity for melanoma. For complexation the AADT-CH2[CH2]nNR2 (n = 1, 2; R = Et, n-Bu) ligand was mixed with a [99mTc]oxotechnetium(V)-glucoheptonate precursor to make the AADT-[99mTc]oxotechnetium(V) complexes in nearly quantitative yield. Structurally analogous nonradioactive oxorhenium(V) complexes were also synthesized and characterized. In vitro sigma-receptor affinity measurements indicate these complexes to possess sigma-affinity in the low micromolar range with K(i) values in the 7.8-26.1 and 0.18-2.3 microM range for the sigma1- and sigma2-receptors, respectively. In vitro cell uptake of the 99mTc complexes in intact B16 murine melanoma cells at 37 degrees C after a 60-min incubation ranged from 12% for complex 2 (n = 1, R = n-Bu) to 68% for complex 4 (n = 2, R = n-Bu). In vivo evaluation of complexes 1-Tc-4-Tc in the C57Bl/B16 mouse melanoma model demonstrated significant tumor localization. Complex 1-Tc (n = 1, R = Et) displayed an in vivo tumor uptake of 7.6% ID/g at 1 h after administration with initial melanoma/blood (M/B), melanoma/spleen (M/S), and melanoma/lung (M/L) ratios >4; these ratios increased to 10.8, 10.1, and 7.3, respectively, at 6 h. While complex 3-Tc (n = 3, R = Et) had an initial tumor uptake of 3.7% ID/g 1 h after administration with M/B, M/S, and M/L ratios >2, a greater tumor retention and slightly faster clearance from nontumor-containing organs resulted in M/B, M/S, and M/L ratios of 19.1, 19.1, and 12.7, respectively, at 6 h. The high tumor uptake and significant tumor/nontumor ratios indicate that such small technetium-99m-based molecular probes can be developed as in vivo diagnostic agents for melanoma and its metastases.

Animals↗
PubMed2001

[Acute gastrointestinal bleeding caused by distinct small intestinal diverticulosis].

HISTORY AND CLINICAL FINDINGS: A 58-year-old man was admitted to our hospital after an acute onset of rectal bleeding. He was known to have had recurrent duodenal ulcerative disease, once with upper gastrointestinal haemorrhage. Clinical examination was remarkable only for rectal bleeding. INVESTIGATIONS: After application of a nasogastric tube cherry-red blood was evacuated. Upper endoscopy showed only very small mucosal erosion in the stomach and coloscopy demonstrated several non-bleeding diverticula. Small bowel enteroclysis showed severe diverticulosis of the duodenum and jejunum. DIAGNOSIS, TREATMENT AND COURSE: We assumed that the extensive duodenojejunal diverticulosis was the most probable cause of this episode of gastrointestinal bleeding because of simultaneous signs of upper and lower gastrointestinal haemorrhage. Because this was the first such episode we preferred a conservative approach. At nineteen months follow-up there was no recurrence of bleeding. CONCLUSION: Gastrointestinal hemorrhage is a common cause of hospitalization. After exclusion of the more common bleeding sources small bowel diverticula should be considered as a possible rare cause. Surgical resection of the bleeding bowel part is the procedure of choice, but one of the major problems in such cases is to locate exactly the bleeding site. If the location is uncertain, a more conservative approach may be preferable, especially in haemodynamically stable patients with first-time diverticular bleeding.

Diverticulum↗
PubMed2000

'3+1' mixed-ligand oxotechnetium(V) complexes with affinity for melanoma: synthesis and evaluation in vitro and in vivo.

'3+1' Mixed-ligand [(99m)Tc]oxotechnetium complexes with affinity for melanoma were synthesized in a one-pot reaction. Complexation of technetium-99m with a mixture of N-R(3-azapentane-1,5-dithiol) [R = Me, Pr, Bn, Et(2)N(CH(2))(2)] and N-(2-dialkylamino)ethanethiol [alkyl = X = Et, Bu, morpholinyl] using Sn(2+) as the reducing agent resulted in the formation of '3+1' mixed-ligand technetium-99m complexes [TcO(SN(R)S)(SNX(2))] in high radiochemical yield (60-98%). In vitro uptake studies in B16 murine melanoma cells indicated a moderate tumor-cell accumulation (40%) of compound 1 [R = Me, X = Et] and a higher accumulation (69%) of compound 2 [R = Me, X = Bu] after a 60-min incubation. In vivo evaluation of compounds 1-6 in the C57Bl6/B16 mouse melanoma model demonstrated tumor localization. Compound 2 displayed the highest accumulation with up to 5% ID/g at 60 min after injection. In vivo, 2 also showed a low blood-pool activity and high melanoma/spleen (4.3) and melanoma/lung (1.9) ratios at 1 h. These results suggest that small technetium-99m complexes could be useful as potential melanoma-imaging agents.

Animals↗
PubMed2000

Permeation studies in vitro and in vivo of potential radiopharmaceuticals with affinity to neuro receptors.

PURPOSE: To check the influence of structural characteristics on their permeation through the blood-brain barrier (BBB), a set of radioactive [99mTc]chelates bearing amine groups was synthesized and tested in vitro as well as in vivo. METHODS: Compounds with different log P and pKa values were obtained by complex forming reactions of [99mTc]pertechnetate with varying substituents. Transport was studied in rats and mice, as well as in an ECV304 cell culture model. RESULTS: In vitro higher permeation was found for compounds with electron attracting substituents in beta-position to the amine group (pKa values 7.4 to 8.3) than for those with more basic amine groups (pKa values > 8.9) even for similar log DH 7.4. In vivo brain uptake between 0.8 and 4.8% of the injected dose (ID) per organ was found for the former, whereas <0.4% ID were present for the latter. CONCLUSIONS: Three structurally diverse classes of [99mTc]chelates showed distinct patterns with regard to brain uptake in vivo and BBB permeability in vitro which could not be predicted by their lipophilicity alone. The close correlation between the data from rats and mice and those obtained with cell cultures render the ECV304 cells an attractive model for the screening of new compounds.

Animals↗
PubMed1999

Determination of dissociation constants of 99mTechnetium radiopharmaceuticals by capillary electrophoresis.

Capillary electrophoresis was applied to investigate pKa values of 99mTc radiotracers used in nuclear medicine. Therefore, the protonation equilibria of the carboxyl groups of 99mTc-mercaptoacetylglycylglycylglycine (99mTc-MAG3) and 99mTc-ethylenecysteine dimer (99mTc-EC) were studied by pH-dependent determination of electrophoretical velocities. 99mTc-ethylenecysteine dimer diethyl ester (99mTc-ECD) was used as a non-protonable standard. The capillary electrophoresis system was equipped with a radioactivity detector. Measurements were performed using a pressure-driven capillary zone electrophoresis which allowed runs even in the low pH range. For the determination of pKa values, the electrophoretical velocities of the analytes were referred to the electrophoretical velocities of tetraphenyle arsonium chloride as a positively charged marker. Calculation of pKa values was accomplished by non-linear curve fitting of both structure-based equilibria equations and sigmoidal decay functions to the experimental data. 99mTc-MAG3 was shown to have a carboxyl group pKa value of 4.22. The value for the carboxyl groups of 99mTc-EC is 2.90 (determined by structure-based equilibria equations), which represents a common value for both carboxyl groups. By the use of sigmoidal functions, similar values were elucidated. As expected, 99mTc-ECD shows no protonation step.

Electrophoresis, Capillary↗
PubMed1998

[Acute liver failure].

Explore the source record for details and available documents.

Chemical and Drug Induced Liver Injury↗
PubMed1995

The ups and downs for children with chronic illnesses.

Children with chronic illnesses have the same basic need for preventive care as their healthy peers. In Michigan a Medicaid Physician Sponsor Plan was established to provide that care for this special population. Incentives and barriers for both physicians and families were identified as well as the advantages to providing care in a managed care delivery system.

Child↗