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- Elvborn, Mikael, et al.
(author)
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Hyperfractionated Treatment with177 Lu-Octreotate Increases Tumor Response in Human Small-Intestine Neuroendocrine GOT1 Tumor Model
- 2022
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In: Cancers. - : MDPI AG. - 2072-6694. ; 14:1
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Journal article (peer-reviewed)abstract
- Radionuclide treatment of patients with neuroendocrine tumors has advanced in the last decades with favorable results using177 Lu-octreotate. However, the gap between the high cure rate in animal studies vs. patient studies indicates a potential to increase the curation of patients. The aim of this study was to investigate the tumor response for different fractionation schemes with177 Lu-octreotate. BALB/c mice bearing a human small-intestine neuroendocrine GOT1 tumor were either mock treated with saline or injected intravenously with a total of 30–120 MBq of177 Lu-octreotate: 1 × 30, 2 × 15, 1 × 60, 2 × 30, 1 × 120, 2 × 60, or 3 × 40 MBq. The tumor volume was measured twice per week until the end of the experiment. The mean tumor volume for mice that received 2 × 15 = 30 and 1 × 30 MBq177 Lu-octreotate was reduced by 61% and 52%, respectively. The mean tumor volume was reduced by 91% and 44% for mice that received 2 × 30 = 60 and 1 × 60 MBq177 Lu-octreotate, respectively. After 120 MBq177 Lu-octreotate, given as 1–3 fractions, the mean tumor volume was reduced by 91–97%. Multiple fractions resulted in delayed regrowth and prolonged overall survival by 20–25% for the 120 MBq groups and by 45% for lower total activities, relative to one fraction. The results indicate that fractionation and hyperfractionation of177 Lu-octreotate are beneficial for tumor reduction and prolongs the time to regrowth. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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- Andersson, Charlotte, et al.
(author)
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Biodistribution of I-131 in mice is influenced by circadian variations
- 2020
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- Effects of radiation and biodistribution of radionuclides are often studied in animal models. Circadian rhythm affects many biological functions and may influence the biokinetics of radionuclides and observed responses. The aim of this study was to investigate if the time during the day of I-131 injection affects the biodistribution and absorbed dose to tissues in mice. Biodistribution studies were conducted on male C57BL/6 N mice for three diurnal time-series: the animals were i.v. injected with 160 kBq I-131 at 8 am, 12 pm or 4 pm. The activity concentration in organs and tissues was measured at 1 h to 7 days after administration and absorbed dose at day 7 was determined. Comparison between the three time-series showed statistically significant differences in activity concentration in all investigated tissues and organs. Administration performed at 12 pm resulted in general in higher absorbed dose to the organs than injection performed at 8 am and 4 pm. Time of day of administration affects the biodistribution of I-131 in mice and consequently the absorbed dose to individual organs. These findings advocate that subsequent biodistribution studies and dosimetry calculations should consider time-point of administration as a variable that could influence the results.
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- Andersson, Charlotte, et al.
(author)
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Diurnal variations in biodistribution of the radionuclide I-131 in mice
- 2016
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In: Swedish Cancer Research Meeting, Gothenburg, 2016, November 7-8.
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Conference paper (other academic/artistic)abstract
- Background: Radionuclides are routinely used to diagnose and treat many different types of cancer. I-131 is a well-established radioisotope used in e.g. treatment of thyroid cancer and neuroblastoma. Accurate knowledge of I-131 biodistribution is essential to correctly estimate the absorbed dose to normal organs and determine potential risks from I-131 exposure, which is especially important when treating children. Many biological functions in living organisms follow a circadian rhythm. Nevertheless, little is known about diurnal variations in radionuclide biodistribution. This study investigates if circadian rhythm affects I-131 biodistribution in mice and absorbed dose to organs and tissues. Materials & Methods: The radioactivity concentration in mice tissues was studied at different time-points after administration of I-131, and absorbed doses were calculated. The effect of circadian rhythm was studied by varying the time of administration. Results: Difference in activity concentration between the administration time-points was observed at many time-points after administration for most investigated tissues. For some organs differences were also observed in the absorbed dose. The highest activity concentration and absorbed dose were found in the thyroid regardless of time of administration. Conclusion: The results demonstrate that the biodistribution of I-131 in mice is influenced by the time of day of administration. These findings advocate that circadian rhythm should be considered in biodistribution studies and suggests that time-point of administration of radiopharmaceuticals containing I-131 for therapy can be further optimized. An optimized time-point could result in higher absorbed dose to the tumor and/or lower absorbed dose to normal tissues.
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| 9. |
- Andersson, Charlotte, et al.
(author)
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The influence of circadian rhythm on the biodistribution of I-131
- 2016
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In: Swedish Radiation Research Association for Young Scientists Workshop, Stockholm, 2016, August 25-26.
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Conference paper (other academic/artistic)abstract
- Background: I-131 is well-established in nuclear medicine. The thyroid is a target organ when treating thyroid cancer with unbound I-131, but also a risk organ in I-131-based radionuclide therapy. Exposure to I-131 can also occur from the environment at nuclear accidents. Accurate knowledge of I-131 biodistribution is essential to correctly estimate the absorbed dose to organs and determine potential risks from both medical and hazard exposure. Many biological functions follow a circadian rhythm. Nevertheless, circadian rhythm remains an unknown factor in radionuclide biodistribution. Aim: The purpose of this study was to investigate if circadian rhythm affects I-131 biodistribution in mice and hence absorbed dose to mouse tissues. Methods: The radioactivity concentration in various tissues was studied at different time points after administration of I-131 and absorbed doses were calculated according to the MIRD formalism. The effect of circadian rhythm was studied by varying the time of administration. Male C57BL/6N mice were i.v. injected with I-131 at 8 am, 12 pm or 4 pm and killed after 1h to 7d. Results: Statistically significant difference in activity concentration and absorbed dose between the three injection series was observed for at least one time point after injection for many tissues. Highest activity concentration and absorbed dose were found in the thyroid. Conclusion: The results demonstrated that the biodistribution of I-131 in mice is influenced by the time of day of administration to a certain extent. These findings advocate that circadian rhythm should be considered in biodistribution studies and dose calculations.
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