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Effects of treatment with (177)Lu-DOTA-Tyr(3)-octreotate on uptake of subsequent injection in carcinoid-bearing nude mice.

Artikel i vetenskaplig tidskrift
Författare Peter Bernhardt
Jenny Oddstig
Lars Kölby
Ola Nilsson
Håkan Ahlman
Eva Forssell-Aronsson
Publicerad i Cancer biotherapy & radiopharmaceuticals
Volym 22
Nummer/häfte 5
Sidor 644-53
ISSN 1084-9785
Publiceringsår 2007
Publicerad vid Institutionen för biomedicin, avdelningen för patologi
Institutionen för kliniska vetenskaper
Sidor 644-53
Språk en
Länkar dx.doi.org/10.1089/cbr.2007.333
Ämnesord Animals, Carcinoid Tumor, metabolism, pathology, radiotherapy, Cell Line, Tumor, Dose-Response Relationship, Radiation, Humans, Indium Radioisotopes, pharmacokinetics, Injections, Intravenous, Lutetium, analysis, pharmacokinetics, Mice, Mice, Nude, Octreotide, administration & dosage, analogs & derivatives, pharmacokinetics, Organometallic Compounds, administration & dosage, pharmacokinetics, Radioisotopes, pharmacokinetics, Time Factors, Tumor Burden, Xenograft Model Antitumor Assays
Ämneskategorier Medicin och Hälsovetenskap

Sammanfattning

PURPOSE: The aim of this study was to analyze the effect therapeutic injections of (177)Lu-DOTA(0)-Tyr(3)]-octreotate (DOTATATE) had on the tumor uptake of a subsequent injection with (111)In-DOTATATE in GOT1-bearing nude mice. METHODS AND MATERIALS: Nude mice, xenografted with the human midgut carcinoid, GOT1, were first intravenously injected with a curative (30 MBq) or a suboptimal (7.5 MBq) amount of (177)Lu-DOTATATE. At various intervals thereafter (4-13 days), a second injection with (111)In-DOTATATE (0.5 MBq) was given. One (1) day after the second injection, the animals were sacrificed, tumor tissues collected, the tumor (111)In and (177)Lu activity concentration determined, and tumor regression/cell density was recorded. RESULTS: In animals given curative amounts, the uptake of (111)In was lower than in untreated animals. On the other hand, a second late injection (3-13 days) after suboptimal amounts resulted in a twofold higher tumor activity concentration versus untreated animals. When the uptake of the curative injection was corrected for tumor cell density, which decreased from 66% to 4% over 2 weeks, an enhanced uptake per tumor cell was observed. The curative and suboptimal amounts resulted in a different uptake and retention of (177)Lu in tumors. The suboptimal amount resulted in a constant activity concentration, while the curative amount resulted in an increased activity concentration over time. CONCLUSIONS: Our results, as presented in this paper, describe how the second injection in a fractionation protocol will be affected by the first therapeutic amount. This new information might be useful in the optimization of radionuclide therapy.

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