| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Dalmo, Johanna, et al.
(författare)
-
Priming increases the anti-tumor effect and therapeutic window of 177Lu-octreotate in nude mice bearing human small intestine neuroendocrine tumor GOT1.
- 2017
-
Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 7:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: 177Lu-[DOTA0, Tyr3]-octreotate (177Lu-octreotate) is used for treatment of patients with somatostatin receptor (SSTR) expressing neuroendocrine tumors. However, complete tumor remission is rarely seen, and optimization of treatment protocols is needed. In vitro studies have shown that irradiation can up-regulate the expression of SSTR1, 2 and 5, and increase 177Lu-octreotate uptake. The aim of the present study was to examine the anti-tumor effect of a 177Lu-octreotate priming dose followed 24 h later by a second injection of 177Lu-octreotate compared to a single administration of 177Lu-octreotate, performed on the human small intestine neuroendocrine tumor cell line, GOT1, transplanted to nude mice. RESULTS: Priming resulted in a 1.9 times higher mean absorbed dose to the tumor tissue per administered activity, together with a reduced mean absorbed dose for kidneys. Priming gave the best overall anti-tumor effects. Magnetic resonance imaging showed no statistically significant difference in tumor response between treatment with and without priming. Gene expression analysis demonstrated effects on cell cycle regulation. Biological processes associated with apoptotic cell death were highly affected in the biodistribution and dosimetry study, via differential regulation of, e.g., APOE, BAX, CDKN1A, and GADD45A. CONCLUSIONS: Priming had the best overall anti-tumor effects and also resulted in an increased therapeutic window. Results indicate that potential biomarkers for tumor regrowth may be found in the p53 or JNK signaling pathways. Priming administration is an interesting optimization strategy for 177Lu-octreotate therapy of neuroendocrine tumors, and further studies should be performed to determine the mechanisms responsible for the reported effects.
|
|
| 15. |
- Druid, Malin, et al.
(författare)
-
Late age- and dose-related effects on the proteome of thyroid tissue in rats after 131I exposure.
- 2024
-
Ingår i: Radiation. - 2673-592X. ; 4:2, s. 149-166
-
Tidskriftsartikel (refereegranskat)abstract
- The physiological process of iodine uptake in the thyroid is used for 131I treatment of thyroid diseases. Children are more sensitive to radiation compared to adults and may react differently to 131I exposure. The aims of this study were to evaluate the effects on thyroid protein expression in young and adult rats one year after 131I injection and identify potential biomarkers related to 131I exposure, absorbed dose, and age. Twelve Sprague Dawley rats (young and adults) were i.v. injected with 50 kBq or 500 kBq 131I and killed twelve months later. Twelve untreated rats were used as age-matched controls. Quantitative proteomics, statistical analysis, and evaluation of biological effects were performed. The effects of irradiation were most prominent in young rats. Protein biomarker candidates were proposed related to age, absorbed dose, thyroid function, and cancer, and a panel was proposed for 131I exposure. In conclusion, the proteome of rat thyroid was differentially regulated twelve months after low-intermediate dose exposure to 131I in both young and adult rats. Several biomarker candidates are proposed for 131I exposure, age, and many of them are known to be related to thyroid function or thyroid cancer. Further research on human samples is needed for validation. Data are avaiable via ProteomeXchange with identifier PXD024786.
|
|
| 16. |
- Elvborn, Mikael, et al.
(författare)
-
Sex-dependence in absorbed dose from I-131 in mice
- 2016
-
Ingår i: Höstmöte med Cancerfondens Planeringsgrupp för Onkologisk Radionuklidterapi, Uppsala, 2016, November 24-25.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)
|
|
| 17. |
|
|
| 18. |
- Elvborn, Mikael, et al.
(författare)
-
The influence of biological sex on the biodistribution of I-131 in mice
- 2016
-
Ingår i: SweRays Workshop, Stockholm, Sweden, Aug 25-26.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: The thyroid is both a risk and target organ in radionuclide therapy. The gland takes up iodine to synthesize thyroidal hormones which are important for various cellular mechanisms throughout the body. 131I is used in nuclear medicine, but hazard exposure can also occur from fallout of nuclear accidents. Physiological differences between the sexes constitute intrinsic variables that are thought to impact the biodistribution of 131I. Aim: The purpose of this study was to assess potential difference between the sexes concerning 131I biodistribution in mice. Methods: In total, 70 C57BL/6N mice (35 males and 35 females) were used in the experiments (n=5/group). Mice were injected intravenously (at 8 am) with 165−175 kBq 131I, prepared in physiological saline, and killed after 1h to 7d following injection. Various tissue samples were collected, weighed, and subjected to gamma counter measurement to determine 131I activity concentration. Results: The results demonstrated clear differences in 131I biodistribution between male and female mice, notably in the kidneys and salivary glands. Statistically significant differences were found for the majority of tissues and time points. Although maximum uptake in the thyroid was similar for both sexes, the decrease of activity concentration after 18h was distinctly slower in females showing statistical significance. Conclusion: Experiments demonstrated that 131I biodistribution differs between the sexes, which would translate to differences in absorbed dose. The extent of difference is tissue-dependent, with markedly different biodistribution in certain tissues. The results advocate that sex should be considered as a variable in biodistribution studies and dose calculations.
|
|
| 19. |
- Elvborn, Mikael, et al.
(författare)
-
The influence of biological sex on thyroid cancer treatment risk assessment
- 2016
-
Ingår i: Swedish Cancer Research Meeting, Gothenburg, 2016, November 7-8.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Researchers are often reluctant towards using females in studies, especially when radiopharmaceuticals and hormonally dependent diseases are concerned. Simultaneously, women are more prone to thyroid-related diseases such as Grave’s disease and Hashimoto’s thyroiditis, with a 7-10 times higher incidence than in men. The thyroid gland synthesizes iodine-containing hormones, which are needed for several cellular processes in the body. I-131 is routinely used in thyroid cancer treatment, and I-131-containing pharmaceuticals are used for treatment of patients with some neuroendocrine tumor types. This study was performed to evaluate possible differences between sexes in tissue uptake of I-131 in mice. Methods: 35 male and 35 female mice (C57BL/6N, n=5/group) were intravenously injected with I-131 at 8 am, and animals were killed 1 h to 7 d after injection. Tissue samples were collected, weighed, and measured to determine I-131 activity concentration. Results: The results indicate differences in I-131 uptake between males and females, especially in the salivary glands and kidneys. In the majority of the tissues and observed time points, statistical significant differences were found. The decrease of activity concentration in thyroid after 18 h was slower for females (statistical significant), though the obtained maximum uptake was similar. Conclusion: The I-131 uptake differs between males and females, which would result in different absorbed doses from exposure to the same amount of I-131. The difference in magnitude is tissue-dependent. The results suggest biological sex to be treated as a variable in dose calculations and risk assessments when treating cancer patients with radiopharmaceuticals containing I-131.
|
|
| 20. |
|
|
