scholarly journals Optimizing the Schedule of PARP Inhibitors in Combination with 177Lu-DOTATATE: A Dosimetry Rationale

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1570
Author(s):  
Andreas Hallqvist ◽  
Johanna Svensson ◽  
Linn Hagmarker ◽  
Ida Marin ◽  
Tobias Rydén ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dose Rate ◽  
Parp Inhibitor ◽  
Somatostatin Receptor ◽  
Absorbed Dose ◽  
Parp Inhibitors ◽  
Initial Increase ◽  
Optimal Timing ◽  
Dose Ratio ◽  
Absorbed Dose Rate

177Lu-DOTATATE for neuroendocrine tumours is considered a low-toxicity treatment and may therefore be combined with other pharmaceuticals to potentiate its efficacy. One approach is to add a poly-[ADP-ribose]-polymerase (PARP) inhibitor to decrease the ability of tumour cells to repair 177Lu-induced DNA damage. To decrease the risk of side effects, the sequencing should be optimized according to the tumour-to-normal tissue enhanced dose ratio (TNED). The aim of this study was to investigate how to enhance 177Lu-DOTATATE by optimal timing of the addition of a PARP inhibitor. Biokinetic modelling was performed based on the absorbed dose to the bone marrow, kidneys and tumour; determined from SPECT/CT and planar images from 17 patients treated with 177Lu-DOTATATE. To investigate the theoretical enhanced biological effect of a PARP inhibitor during 177Lu-DOTATATE treatment, the concept of relative biological effectiveness (RBE) was used, and PARP inhibitor administration was simulated over different time intervals. The absorbed dose rate for the tumour tissue demonstrated an initial increase phase until 12 h after infusion followed by a slow decrease. In contrast, the bone marrow showed a rapid initial dose rate decrease. Twenty-eight days after infusion of 177Lu-DOTATATE, the full absorbed dose to the bone marrow and kidney was reached. Using an RBE value of 2 for both the tumour and normal tissues, the TNED was increased compared to 177Lu-DOTATATE alone. According to the modelling, the PARP inhibitor should be introduced approximately 24 h after the start of 177Lu-DOTATATE treatment and be continued for up to four weeks to optimize the TNED. Based on these results, a phase I trial assessing the combination of olaparib and 177Lu-DOTATATE in somatostatin receptor-positive tumours was launched in 2020 (NCT04375267).

HUMAN EXPOSURE TO BACKGROUND RADIATION IN ORTUM, KENYA

2019 ◽  
Vol 188 (1) ◽  
pp. 98-108
Author(s):  
F O Wanjala ◽  
N O Hashim ◽  
D Otwoma ◽  
C Nyambura ◽  
J Kebwaro ◽  
...  
Keyword(s):  
Dose Rate ◽  
Human Exposure ◽  
Activity Concentration ◽  
Background Radiation ◽  
Absorbed Dose ◽  
Threshold Values ◽  
Absorbed Dose Rate ◽  
The World ◽  
Average Activity ◽  
Terrestrial Radionuclides

Abstract The activity concentration of radionuclides 238U, 232Th and 40K in soil and the absorbed dose rate (ADRA) at 1 m above the ground in Ortum was determined. The activity concentration in soils ranged from 33 to 85, 20 to 67 and 148–1019 Bq kg–1, respectively with an average of 40 ± 1.43, 56 ± 1.46 and 425 ± 19.24 Bq kg–1, respectively. The activity concentration of 232Th and 238U was found to reduce with increasing depth while that of 40K increased with increasing depth. The average activity concentration in soil was higher than the world average values. The average ADRA in air at 1 m above the ground was found to be 112 ± 29.6 nGy h–1. The soil and rocks in Ortum are recommended for use because the activity concentration of the terrestrial radionuclides is lower than the recommended threshold values.

Assessment of natural radioactivity levels and the associated radiological hazards in some building materials from Mayo-Kebbi region, Chad

2018 ◽  
Vol 53 (4) ◽  
pp. 265-278 ◽  
Author(s):  
S. Penabei ◽  
D. Bongue ◽  
P. Maleka ◽  
T. Dlamini ◽  
Saïdou ◽  
...  
Keyword(s):  
Dose Rate ◽  
Natural Radioactivity ◽  
Building Materials ◽  
Hazard Index ◽  
Absorbed Dose ◽  
Radiation Hazard ◽  
Absorbed Dose Rate ◽  
Activity Concentrations ◽  
Radiological Hazards ◽  
Radiation Hazard Index

In order to assess the levels of natural radioactivity and the associated radiological hazards in some building materials of the Mayo-Kebbi region (Chad), a total of nineteen samples were collected on the field. Using a high resolution γ-ray spectrometry system, the activity concentrations of radium (226Ra), thorium (232Th) and potassium (40K) in these samples have been determined. The measured average activity concentrations range from 0.56 ± 0.37 Bq kg−1 to 435 ± 7 Bq kg−1, 1.3 ± 0.6 Bq kg−1 to 50.6 ± 1.1 Bq kg−1 and 4.3 ± 2.0 Bq kg−1 to 840 ± 9 Bq kg−1, for 226Ra, 232Th and 40K, respectively. The highest 226Ra average activities is found in soil brick samples of Zabili. The highest mean value of 232Th and 40K concentrations are found in soil brick samples of Madajang. The activity concentration and the radium equivalent activity (Raeq) have been compared to other studies done elsewhere in the world. Their average values are lower than most of those of countries with which the comparison has been made. Were also evaluated, the external radiation hazard index, the internal radiation hazard index, the indoor air absorbed dose rate, the outdoor air absorbed dose rate, the activity utilization index, the annual effective dose, the annual gonadal dose equivalent, the representative level index, as well as, the excess lifetime cancer risk. In accordance with the criterion of the Organization for Economic Cooperation and Development, our results show that soil brick samples of Zabili and Madajang increases the risk of radiation exposure, thereby the possibility of developing cancer by people living in this environment. Based on these findings, brick samples from Zabili and Madajang are not recommended for construction purposes. All other sample materials have properties that are acceptable for use as building materials in terms of radiation hazard.

scholarly journals Total air absorbed dose rate map, Hutcherson Lake, Saskatchewan, NTS 64M/7

2001 ◽  
Author(s):  
J M Carson ◽  
P B Holman ◽  
R B K Shives ◽  
K L Ford ◽  
C T Harper ◽  
...  
Keyword(s):  
Dose Rate ◽  
Absorbed Dose ◽  
Absorbed Dose Rate

scholarly journals High Terrestrial Radiation Level in an Active Tin-Mine at Jos South, Nigeria

2020 ◽  
Vol 24 (3) ◽  
pp. 435-442 ◽  
Author(s):  
M. Atipo ◽  
O. Olarinoye ◽  
B. Awojoyogbe ◽  
M. Kolo
Keyword(s):  
Gamma Radiation ◽  
Dose Rate ◽  
Technological Development ◽  
Absorbed Dose ◽  
Ground Level ◽  
Absorbed Dose Rate ◽  
Lifetime Cancer Risk ◽  
Radiation Level ◽  
Background Gamma Radiation ◽  
The Mean

Mineral mining and milling can be a source of national economic and technological development. However, mining of minerals has been confirmed to disturb the natural distribution of radioisotopes in the soil, air and water bodies in the biota. In an attempt to evaluate the radiological burden resulting from tin mining activities at Rayfield-Du area of Jos, the background gamma-radiation level in the mine was measured via a well calibratedhand-held dosimeter placed at 1 m above ground level. The mean absorbed dose rate, annual effective dose rate and excess lifetime cancer risk for the mine was 0.83 μSvh-1; 1.44 mSv-1 and 0.005 respectively. Generally, dose rates were higher in the mine pits and processing areas as compared to administrative areas of the mine. The mean measured dose rate and calculated dose parameters for the mine were all high when compared to the regulatory limit for public exposure. The potential of developing radiation-induced health defects as a result of high radiation absorbed dose rate by the miners and dwellers around the mine is highly probable.  Keywords: Gamma-radiation; mine; absorbed dose rate; radiation exposure.

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