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| 2. |
- Alattar, Abdul Ghani, et al.
(författare)
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Recombinant alpha(1)-Microglobulin (rA1M) Protects against Hematopoietic and Renal Toxicity, Alone and in Combination with Amino Acids, in a Lu-177-DOTATATE Mouse Radiation Model
- 2023
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Ingår i: Biomolecules. - 2218-273X. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Lu-177-DOTATATE peptide receptor radionuclide therapy (PRRT) is used clinically to treat metastasized or unresectable neuroendocrine tumors (NETs). Although Lu-177-DOTATATE is mostly well tolerated in patients, bone marrow suppression and long-term renal toxicity are still side effects that should be considered. Amino acids are often used to minimize renal radiotoxicity, however, they are associated with nausea and vomiting in patients. alpha (1)-microglobulin (A1M) is an antioxidant with heme- and radical-scavenging abilities. A recombinant form (rA1M) has previously been shown to be renoprotective in preclinical models, including in PRRT-induced kidney damage. Here, we further investigated rA1M's renal protective effect in a mouse Lu-177-DOTATATE model in terms of administration route and dosing regimen and as a combined therapy with amino acids (Vamin). Moreover, we investigated the protective effect of rA1M on peripheral blood and bone marrow cells, as well as circulatory biomarkers. Intravenous (i.v.) administration of rA1M reduced albuminuria levels and circulatory levels of the oxidative stress-related protein fibroblast growth factor-21 (FGF-21). Dual injections of rA1M (i.e., at 0 and 24 h post-Lu-177-DOTATATE administration) preserved bone marrow cellularity and peripheral blood reticulocytes. Administration of Vamin, alone or in combination with rA1M, did not show any protection of bone marrow cellularity or peripheral reticulocytes. In conclusion, this study suggests that rA1M, administered i.v. for two consecutive days in conjunction with Lu-177-DOTATATE, may reduce hematopoietic and kidney toxicity during PRRT with Lu-177-DOTATATE.
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| 4. |
- Piñero-García, Francisco, et al.
(författare)
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Biodistribution of 210Po in seafood and risk assessment for consumers in Sweden
- 2023
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Ingår i: Food Control. - 0956-7135. ; 151
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Tidskriftsartikel (refereegranskat)abstract
- Seafood consumption per capita, in Sweden, is larger than World and European average. Although, 36% of Swedes consume seafood meals at least two times per week, the Swedish National Food Agency advises the necessity to increase this ratio. Seafood is one of the main entrances of 210Po in the human food chain. Due to the high radiotoxicity, the intake of 210Po plays an important role in the human health, even in extremely small quantities. In this study, 114 seafood samples representing 52 different marine species were analyzed. The biodistribution of 210Po in seafood species were not uniformly distributed being higher in digestive system and gonads, and lower in seafood muscle. The activity concentration of 210Po in fish ranged between 0.01 and 26 Bq/kg with an average value of 4 Bq/kg, whereas in shellfish fluctuated between 0.1 and 239 Bq/kg, with a mean concentration of 18 Bq/kg. In general, the activity concentration of 210Po in processed products were lower than fresh samples due to the decay of 210Po from seafood capture to purchase. However, in boiled seafood such as Norway Lobster, with short elapsed time from collection to purchase, the boil samples presented higher activity concentration of 210Po than fresh products. The results of the study showed that the annual intake of 210Po via seafood consumption in Sweden exponentially increased by age and it was slightly higher in males than females. As a result, the annual committed dose ranged from 60 to 154 μSv, with an average value of 103 ± 31 μSv, being controlled by fish consumption below 14 years old and by seafood consumption above 14 years old. Finally, the committed effective dose could increase up to 479 μSv/y for population group with higher seafood consumption.
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| 5. |
- Piñero-García, Francisco, et al.
(författare)
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Biodistribution of naturally occurring radionuclides and radiocesium in wild European perch (Perca fluviatilis).
- 2023
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Ingår i: Ecotoxicology and environmental safety. - 1090-2414. ; 260
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Tidskriftsartikel (refereegranskat)abstract
- Wild European perch (Perca fluviatilis) is one of the most important freshwater fish species, in Sweden, due to its widespread and his value for recreational fishing. Little it is known regarding the biodistribution of naturally occurring radionuclides such as 238U, 234U, 226Ra, 210Po in perch. Therefore, in this study, perches from five lakes located in different counties in Sweden were collected to investigate the biodistribution of 238U, 234U, 226Ra, 210Po and 137Cs in organs and tissues of perch as well as their radiological impact. The results showed that uranium radionuclides ranged between 0.1 and 6 Bq/kg with an average value of 1.1 ± 1.5 Bq/kg. 226Ra varied from 0.4 to 8 Bq/kg with a mean concentration of 1.7 ± 1.9 Bq/kg. The ranged of 210Po was 0.5 - 250 Bq/kg, with an average value of 24 ± 52 Bq/kg. On the other hand, the highest activity concentration of 137Cs, 151 ± 1 Bq/kg, was detected in muscle samples of perch from Redsjösjön lake. For uranium radionuclides and 226Ra uptake from water is the main source whereas for 210Po and 137Cs the uptake is controlled by the perch diet. Regarding naturally occurring radionuclides, the perch tended to accumulated uranium radionuclides in fins, gills, and skin; 226Ra in bones, fins and skin and 210Po in the organs linked to digestive system. Finally, in case of consumption, it is advised the consumption of skinned fillets of perch due to the higher bioaccumulation of the radionuclides investigated in the skin and scales.
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| 6. |
- Rassol, Nishte, et al.
(författare)
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Co-administration with A1M does not influence apoptotic response of 177Lu-octreotate in GOT1 neuroendocrine tumors
- 2023
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Ingår i: Scientific Reports. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Recombinant α1-microglobulin (A1M) is a proposed radioprotector during 177Lu-octreotate therapy of neuroendocrine tumors (NETs). To ensure a maintained therapeutic effect, we previously demonstrated that A1M does not affect the 177Lu-octreotate induced decrease in GOT1 tumor volume. However, the underlying biological events of these findings are still unknown. The aim of this work was to examine the regulation of apoptosis-related genes in GOT1 tumors short-time after i.v. administration of 177Lu-octreotate with and without A1M or A1M alone. Human GOT1 tumor-bearing mice received 30 MBq 177Lu-octreotate or 5 mg/kg A1M or co-treatment with both. Animals were sacrificed after 1 or 7 days. Gene expression analysis of apoptosis-related genes in GOT1 tissue was performed with RT-PCR. In general, similar expression patterns of pro- and anti-apoptotic genes were found after 177Lu-octreotate exposure with or without co-administration of A1M. The highest regulated genes in both irradiated groups compared to untreated controls were FAS and TNFSFRS10B. Administration of A1M alone only resulted in significantly regulated genes after 7 days. Co-administration of A1M did not negatively affect the transcriptional apoptotic response of 177Lu-octreotate in GOT1 tumors.
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| 7. |
- Thomas, Rimon, et al.
(författare)
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Analysis of radioactivity in commercially available products aiming to improve health and wellness
- 2023
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Ingår i: Radiation Protection Dosimetry. - 0144-8420 .- 1742-3406. ; 199:13
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Tidskriftsartikel (refereegranskat)abstract
- There are products available on the online market that claim to contain unique ‘energies’ that can improve health and wellness by eliminating toxins and pains and energising food and drinking water. We investigated these products by alpha and gamma spectrometry, and the analysis showed that they contained a few to hundreds of kilobecquerels per kilogram of naturally occurring radionuclides from the 232Th and 238U series. The committed effective dose for an adult drinking water that had been in contact with these products just once was estimated to 12 nSv. Considering a worst-case scenario for the workers inhaling the radioactive substance, 1 d of work would result in an effective dose of 0.39 mSv. The product descriptions do not mention the radionuclide content, and concerns are raised for the consumers and workers exposed to these products with no knowledge of the radioactive content.
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| 8. |
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| 9. |
- Elvborn, Mikael, et al.
(författare)
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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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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:1
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Tidskriftsartikel (refereegranskat)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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| 10. |
- Langen, Britta, et al.
(författare)
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Age and sex effects across the blood proteome after ionizing radiation exposure can bias biomarker screening and risk assessment
- 2022
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Molecular biomarkers of ionizing radiation (IR) exposure are a promising new tool in various disciplines: they can give necessary information for adaptive treatment planning in cancer radiotherapy, enable risk projection for radiation-induced survivorship diseases, or facilitate triage and intervention in radiation hazard events. However, radiation biomarker discovery has not yet resolved the most basic features of personalized medicine: age and sex. To overcome this critical bias in biomarker identification, we quantitated age and sex effects and assessed their relevance in the radiation response across the blood proteome. We used high-throughput mass spectrometry on blood plasma collected 24 h after 0.5 Gy total body irradiation (15 MV nominal photon energy) from male and female C57BL/6 N mice at juvenile (7-weeks-old) or adult (18-weeks-old) age. We also assessed sex and strain effects using juvenile male and female BALB/c nude mice. We showed that age and sex created significant effects in the proteomic response regarding both extent and functional quality of IR-induced responses. Furthermore, we found that age and sex effects appeared non-linear and were often end-point specific. Overall, age contributed more to differences in the proteomic response than sex, most notably in immune responses, oxidative stress, and apoptotic cell death. Interestingly, sex effects were pronounced for DNA damage and repair pathways and associated cellular outcome (pro-survival vs. pro-apoptotic). Only one protein (AHSP) was identified as a potential general biomarker candidate across age and sex, while GMNN, REG3B, and SNCA indicated some response similarity across age. This low yield advocated that unisex or uniage biomarker screening approaches are not feasible. In conclusion, age- and sex-specific screening approaches should be implemented as standard protocol to ensure robustness and diagnostic power of biomarker candidates. Bias-free molecular biomarkers are a necessary progression towards personalized medicine and integral for advanced adaptive cancer radiotherapy and risk assessment.
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