| 1. |
- Bernhardt, Peter, 1966, et al.
(författare)
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Effects of treatment with (177)Lu-DOTA-Tyr(3)-octreotate on uptake of subsequent injection in carcinoid-bearing nude mice.
- 2007
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Ingår i: Cancer biotherapy & radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 22:5, s. 644-53
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 2. |
- Oddstig, Jenny, 1978, et al.
(författare)
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A novel photon radiation detector system for in vitro biokinetic measurements.
- 2005
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Ingår i: Cancer biotherapy & radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 20:6, s. 629-38
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: This study evaluates a novel photon radiation detector system for in vitro biokinetic measurements. METHODS: A cell-culture well can be considered to consist of two different compartments: the cells and the medium. By placing the well on a lead-collimated scintillation (NaI(T1)) detector, changes in activity distribution between the compartments will result in changes in count rates owing to the efficiency ratio (ER) between the cells and the medium. The ER depends on differences in detection solid angles for the compartments and differences in attenuation of photons emitted from the compartments. Evaluation of the optimal measuring geometries for the detector system was done by Monte Carlo (MC) simulations. The detector system was tested in two different in vitro situations. RESULTS: The MC simulations showed that the most optimal detector system was obtained by using a lead-collimated well crystal. Both the MC simulations and the experiments have proven the usability of the system. CONCLUSIONS: The detector system was demonstrated to be of value for biokinetic studies. The cellular binding of radiolabeled substances can be determined with high precision, and real-time measurements can be performed on a cell culture without harvesting the cells.
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| 3. |
- Oddstig, Jenny, 1978, et al.
(författare)
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Inhomogeneous activity distribution of (177)Lu-DOTA (0)-Tyr (3)-octreotate and effects on somatostatin receptor expression in human carcinoid GOT1 tumors in nude mice.
- 2012
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Ingår i: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. - : Springer Science and Business Media LLC. - 1423-0380. ; 33:1, s. 229-239
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the activity distribution in neouroendocrine tumors after diagnostic, or therapeutic, amounts of [(177)Lu-DOTA(0)-Tyr(3)]-octreotate and to investigate how the activity distribution influences the absorbed dose. Furthermore, the activity distribution of a second administration of radiolabeled octreotate was studied. Nude mice with subcutaneously grown human midgut carcinoid (GOT1) were injected intravenously with different amounts of (177)Lu-octreotate. At different time points thereafter (4h to 13days), a second injection of [(111)In-DOTA(0)-Tyr(3)]-octreotate was given to estimate the somatostatin receptor (sstr) expression. The activity distribution in the tumors was then determined. Monte Carlo simulations with PENELOPE were performed for dosimetry. Fifty-one out of 58 investigated tumors showed a lower activity concentration in the peripheral part than in the central part of the tumor. The amount of activity injected, or time after administration, did neither influence the relative activity nor the sstr distribution in the tumor. After an initial down-regulation (at 4-24h), there was an up-regulation of sstr (1.5-2 times, at 7-14days). Monte Carlo simulations demonstrated an inhomogeneous absorbed dose distribution in the tumor using (177)Lu, with twice as high absorbed dose centrally than peripherally. The high activity concentration centrally and the up-regulation of sstr demonstrated will facilitate fractionated therapy using radiolabeled somatostatin analogues if similar results will be obtained also in patients. The inhomogeneous activity distribution in the tumor has to be taken into account when the absorbed dose distribution in tumor is calculated.
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| 4. |
- Oddstig, Jenny, 1978, et al.
(författare)
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Radiation-induced up-regulation of somatostatin receptor expression in small cell lung cancer in vitro.
- 2006
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Ingår i: Nuclear medicine and biology. - : Elsevier BV. - 0969-8051. ; 33:7, s. 841-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The internalization of radiolabeled somatostatin analogs into tumor cells is of great importance for radionuclide therapy. It has previously been shown that some radiolabeled somatostatin analogs are internalized through receptor-mediated endocytosis. The development of methods that increase the number of receptors on tumor cells is important to further improve the internalization of radionuclides. The aim of this study was to investigate the possibility of inducing up-regulation of the somatostatin receptor (sstr) expression on tumor cells by external-beam irradiation. METHODS: Human small cell lung cancer (SCLC) cells were irradiated to absorbed doses of 2-8 Gy, and the uptake of 177Lu-DOTA-Tyr3-octreotate was measured 1-7 days after irradiation. The sstr2 mRNA expression was determined by quantitative reverse transcriptase-polymerase chain reaction. RESULTS: The uptake of 177Lu-DOTA-Tyr3-octreotate was 1.5-3 times higher in cells irradiated to 4 Gy than in nonirradiated cells, and the highest uptake occurred 1 and 3-5 days after irradiation. The uptake of 177Lu-DOTA-Tyr3-octreotate was similar for cells irradiated to 2, 4, 6 and 8 Gy. The sstr2 mRNA expression was twice as high in the cells irradiated to 4 Gy than in the nonirradiated cells. CONCLUSIONS: The uptake of 177Lu-DOTA-Tyr3-octreotate increased in SCLC cells after exposure to irradiation, probably due to up-regulation of sstr expression. These results may be important in optimizing the treatment of tumors expressing sstr using radiolabeled somatostatin analogs.
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| 5. |
- Oddstig, Jenny, 1978, et al.
(författare)
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Radiation Induces Up-Regulation of Somatostatin Receptors 1, 2, and 5 in Small Cell Lung Cancer In Vitro Also at Low Absorbed Doses.
- 2011
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Ingår i: Cancer biotherapy & radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1557-8852 .- 1084-9785. ; 26:6
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background: Radiation can be used to up-regulate the expression of the somatostatin receptor (sstr) subtype 2 in small cell lung cancer (SCLC) cells at absorbed doses of 2?8 Gy. Increased sstr expression results in increased binding of radiolabeled somatostatin analogs to the tumor cell, which enhances the efficacy of systemic radionuclide therapy. The aim of this study was to determine if lower absorbed doses could up-regulate sstr2 expression, and possibly influence other sstr subtypes. Methods: Human H69 SCLC cells were irradiated with an absorbed dose of 0.12?6.0 Gy and the sstr mRNA expression 3 days after irradiation was measured by quantitative real-time polymerase chain reaction for sstr1?5. At the same time point was the binding of [(177)Lu]-DOTA(0)-Tyr(3)-octreotate to the cells measured after irradiation to an absorbed dose of 0.12?2.0 Gy and compared to the binding to nonirradiated cells. Results: mRNA expression of sstr1, sstr2, and sstr5 was increased by a factor of 1.5?2 in cells irradiated with absorbed doses?4 Gy and the binding of [(177)Lu]-DOTA(0)-Tyr(3)-octreotate was, accordingly, 2?3 times higher to irradiated cells for all absorbed doses, except 0.25 Gy. Conclusion: The binding of [(177)Lu]-DOTA(0)-Tyr(3)-octreotate was increased after radiation exposure. This increase was observed at low absorbed doses in parallel with up-regulation of sstr1, sstr2, and sstr5 mRNA.
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