| [99mTc]oxotechnetium(V) complexes amine-amide-dithiol chelates with dialkylaminoalkyl substituents as potential diagnostic probes for malignant melanoma. | |
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MedLine Citation:
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PMID: 11543682 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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[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. |
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Authors:
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M Friebe; A Mahmood; C Bolzati; A Drews; B Johannsen; M Eisenhut; D Kraemer; A Davison; A G Jones |
Publication Detail:
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Type: In Vitro; Journal Article |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 44 ISSN: 0022-2623 ISO Abbreviation: J. Med. Chem. Publication Date: 2001 Sep |
Date Detail:
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Created Date: 2001-09-06 Completed Date: 2001-10-11 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: United States |
Other Details:
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Languages: eng Pagination: 3132-40 Citation Subset: IM |
Affiliation:
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Department of Radiology, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Binding, Competitive Brain / metabolism Chelating Agents / chemical synthesis*, chemistry Crystallography, X-Ray Guinea Pigs Humans Melanoma, Experimental / metabolism* Mice Mice, Inbred C57BL Neoplasm Transplantation Organotechnetium Compounds / chemical synthesis*, chemistry, pharmacokinetics Radioligand Assay Receptors, sigma / metabolism Stereoisomerism Structure-Activity Relationship Sulfhydryl Compounds / chemical synthesis*, chemistry Tissue Distribution Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/Chelating Agents; 0/Organotechnetium Compounds; 0/Receptors, sigma; 0/Sulfhydryl Compounds |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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