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Design, synthesis and biological evaluation of negatively charged ¹¹¹In-DTPA-octreotide derivatives

, : Design, synthesis and biological evaluation of negatively charged ¹¹¹In-DTPA-octreotide derivatives. Bioorganic & Medicinal Chemistry 22(4): 1377-1382

Our previous studies indicated that (111)In-diethylenetriaminepentaacetic acid ((111)In-DTPA)-octreotide derivatives with an additional negative charge by replacing N-terminal d-phenylalanine (d-Phe) with an acidic amino acid such as l-aspartic acid (Asp) or its derivative exhibited low renal radioactivity levels when compared with (111)In-DTPA-D-Phe(1)-octreotide. On the basis of the findings, we designed, synthesized and evaluated two Asp-modified (111)In-DTPA-conjugated octreotide derivatives, (111)In-DTPA-Asp(1)-octreotide and (111)In-DTPA-Asp(0)-D-Phe(1)-octreotide. While (111)In-DTPA-Asp(1)-octreotide showed negligible AR42J cell uptake, (111)In-DTPA-Asp(0)-D-Phe(1)-octreotide exhibited AR42J cell uptake similar to that of (111)In-DTPA-D-Phe(1)-octreotide. When administered to AR42J tumor-bearing mice, (111)In-DTPA-Asp(0)-D-Phe(1)-octreotide exhibited renal radioactivity levels significantly lower than did (111)In-DTPA-D-Phe(1)-octreotide at 1 and 3 h post-injection. No significant differences were observed in tumor accumulation between (111)In-DTPA-Asp(0)-D-Phe(1)-octreotide and (111)In-DTPA-D-Phe(1)-octreotide after 1 and 3h injection. The findings in this study suggested that an interposition of an Asp at an appropriate position in (111)In-DTPA-D-Phe(1)-octreotide would constitute a useful strategy to develop (111)In-DTPA-D-Phe(1)-octreotide derivatives of low renal radioactivity levels while preserving tumor accumulation.


PMID: 24457092

DOI: 10.1016/j.bmc.2013.12.063

Other references

Porter, C., 1949: Food and drink infections. Medical Officer 81(12): 125-127

Carvalho, C.Sofia.; Vlachakis, D.; Tsiliki, G.; Megalooikonomou, V.; Kossida, S., 2013: Protein signatures using electrostatic molecular surfaces in harmonic space. We developed a novel method based on the Fourier analysis of protein molecular surfaces to speed up the analysis of the vast structural data generated in the post-genomic era. This method computes the power spectrum of surfaces of the molecular el...

Tane, S.; Komatsu, A.; Kondo, K., 1983: Ultrasonic diagnosis in ophthalmology. 17. High frequency electronic linear scanning ultrasonic diagnosis equipment for ocular imaging diagnosis. Nippon Ganka Gakkai Zasshi 87(9): 722-728

Saylor, B.J.; Stencil, J.C.; DeVasto, M.A.; Bhattacharyya, P.; Fitz, T., 2011: Whole rock geochemical analyses of sheared granitic rocks from Mountain, Wisconsin. Proceedings and Abstracts - Institute on Lake Superior Geology. Meeting 57, 1

Kaushish, S.K.; Arora, K.L.; Dhanda, O.P., 1973: Studies on reproduction in sheep. II. Time of parturition. Of 72 Nali, 29 Lohi and 31 Nellore X Nali and Mandya X Nali ewes the majority lambed between 03.00 and 06.00 or between 15.00 and 18.00 h. There were significant differences between the breeds in time of lambing.

Kushwaha, Ks, 1971: A new record, Carcellia buitenzorgiensis Bar. (Diptera: Tachinidae) as a parasite of Psalis pennatula Fabr. (Lepidoptera: Lymantriidae). Science and Cult7(5): 243

Drover, D.R.; Angst, M.S.; Valle, M.; Ramaswamy, B.; Naidu, S.; Stanski, D.R.; Verotta, D., 2002: Input characteristics and bioavailability after administration of immediate and a new extended-release formulation of hydromorphone in healthy volunteers. Background: To compare the pharmacokinetics of intravenous, oral immediate-release (IR), and oral extended-release (OROS(R)) formulations of hydromorphone. Methods: In this randomized, six-session, crossover-design study, 12 subjects received hydr...

Arbustini, E.; Grasso, M.; Diegoli, M.; Pucci, A.; Bramerio, M.; Ardissino, D.; Angoli, L.; de Servi, S.; Bramucci, E.; Mussini, A., 1991: Coronary atherosclerotic plaques with and without thrombus in ischemic heart syndromes: a morphologic, immunohistochemical, and biochemical study. We investigated incidence, severity, and distribution of coronary atherosclerosis, acute thrombosis, and plaque fissuring in ischemic heart disease (both unstable-acute syndromes and chronic ischemia) and in nonischemic controls. We also studied t...

Dohgu, S.; Fleegal-DeMotta, M.A.; Banks, W.A., 2012: Lipopolysaccharide-enhanced transcellular transport of HIV-1 across the blood-brain barrier is mediated by luminal microvessel IL-6 and GM-CSF. Elevated levels of cytokines/chemokines contribute to increased neuroinvasion of human immunodeficiency virus type 1 (HIV-1). Previous work showed that lipopolysaccharide (LPS), which is present in the plasma of patients with HIV-1, enhanced trans...

Crombie, L.; Games, D.E.; Haskins, N.J.; Reed, G.F., 1972: Extractives of Mammea americana L. V. The insecticidal compounds. Journal of the Chemical Society. Perkin Transactions 1 18: 2255-2260