This study aimed to carry out the preclinical studies of 89ZrZr-DFO-Bevacizumab. The radiolabeled compound was prepared with radiochemical purity >99% (ITLC), and a specific activity of 74 GBq/g. ...Cellular studies indicated the great capability of 89ZrZr-DFO-Bevacizumab for binding to SKOV3 cell lines. High accumulation was observed in the tumor. The liver and spleen received the highest absorbed dose with 1.12 and 0.72 mGy/MBq, respectively. This radiopharmaceutical can be considered as a suitable PET agent for VEGF-expressing ovarian cancer imaging.
•89ZrZr-Bevacizumab was prepared with RCP >99% and specific activity of 74 GBq/g.•89Zr was produced by 89Y(p,n)89Zr reaction using a 30 MeV cyclotron.•Cellular studies indicated great capability of compound for binding to SKOV3 cells.•High accumulation of complex was observed in tumor sites of tumor-bearing nude mice.•Liver received the highest absorbed dose with 1.12 mGy/MBq.
Purpose
The knowledge of the contribution of anatomical and physiological parameters to interindividual pharmacokinetic differences could potentially be used to improve individualized treatment ...planning for radionuclide therapy. The aim of this study was therefore to identify the physiologically based pharmacokinetic (PBPK) model parameters that determine the interindividual variability of absorbed doses (ADs) to kidneys and tumor lesions in therapy with 177Lu‐labeled PSMA‐targeting radioligands.
Methods
A global sensitivity analysis (GSA) with the extended Fourier Amplitude Sensitivity Test (eFAST) algorithm was performed. The whole‐body PBPK model for PSMA‐targeting radioligand therapy from our previous studies was used in this study. The model parameters of interest (input of the GSA) were the organ receptor densities R0, the organ blood flows f, and the organ release rates λ. These parameters were systematically sampled NE times according to their distribution in the patient population. The corresponding pharmacokinetics were simulated and the ADs (model output) to kidneys and tumor lesions were collected. The main effect Si and total effect STi were calculated using the eFAST algorithm based on the variability of the model output: The main effect Si of input parameter i represents the reduction in variance of the output if the “true” value of parameter i would be known. The total effect STi of an input parameter i represents the proportion of variance remaining if the “true” values of all other input parameters except for i are known. The numbers of samples NE were increased up to 8193 to check the stability (i.e., convergence) of the calculated main effects Si and total effects STi.
Results
From the simulations, the relative interindividual variability of ADs in the kidneys (coefficient of variation CV = 31%) was lower than that of ADs in the tumors (CV up to 59%). Based on the GSA, the most important parameters that determine the ADs to the kidneys were kidneys flow (Si = 0.36, STi = 0.43) and kidneys receptor density (Si = 0.25, STi = 0.30). Tumor receptor density was identified as the most important parameter determining the ADs to tumors (Si and STi up to 0.72).
Conclusions
The results suggest that an accurate measurement of receptor density and flow before therapy could be a promising approach for developing an individualized treatment with 177Lu‐labeled PSMA‐targeting radioligands.
The attentive consideration of absorbed dose impact on the breast, a radiosensitive organ, remains pivotal in coronary computed tomography angiography (CCTA). Additionally, the thyroid is subjected ...to scatter radiation during this diagnostic procedure. The primary objective of this study was to comprehensively investigate and quantify the absorbed dose, effective dose, and lifetime attributable risks (LARs) associated with breast and thyroid cancers in the context of CCTA. This investigation enrolled a cohort of 180 patients (90 men and 90 women) who underwent CCTA utilizing three distinct CT scanners: the SOMATOM Definition AS 128 slice (Siemens 128), the Lightspeed VCT 64 Slice (GE 64), and the Brilliance 64 Slice (Philips 64). The precise quantification of absorbed doses to the breast and thyroid was achieved through the utilization of a thermoluminescence dosimeter (TLD). LAR for breast and thyroid cancers was evaluated in accordance with the BEIR VII report. Kruskal–Wallis test was employed to compare the means of absorbed doses and LARs. The average absorbed doses to the breast during CCTA with Siemens 128, GE 64, and Philips 64 scanners were 116.32 ± 39.02, 82.88 ± 18.33, and 84.11 ± 15.18 mGy, respectively (P < 0.05). Correspondingly, the average LAR for breast cancer was found to be 84, 68, and 52 cases per 100,000 persons, respectively. Notably, a significant discrepancy in breast cancer LARs was observed among different age groups (P < 0.05). Regarding thyroid doses with Siemens 128, GE 64, and Philips 64 scanners, average values were 11.82 ± 7.51, 12.20 ± 10.87, and 14.49 ± 5.43 mGy, respectively (P > 0.05). Additionally, the average LAR for thyroid cancer was determined as 0.32, 0.56, and 0.22 cases per 100,000 persons, respectively. Across all age groups, the LAR for thyroid cancer exhibited higher values among women compared to men. However, these differences did not achieve statistical significance (P > 0.05), indicating a need for further investigation. The findings prominently indicated high absorbed doses to the breast in CCTA using protocols investigated in this study (with an average of 93.7 ± 30.26 mGy). Particularly, the LAR for breast cancer was higher among younger women, specifically those aged between 20 and 40 years (249 cases per 100,000). These results underscore the necessity for further justification and optimization of CCTA protocols.
•The absorbed dose to the breast in CCTA utilizing current protocols is high (94 mGy).•The average LAR of breast cancer in CCTA is higher (249 cases per 100,000) for women aged between 20 and 40 years.•The LAR of thyroid cancer in CCTA is higher for women compared to the men but not statistically significant (P > 0.05).•Further justification and optimization of CCTA protocols is needed.
This paper focuses on the natural radioactivity concentrations of 238U, 232Th, and 40K in the eruptive products of the Gölcük Volcano (SW Turkey) and its environmental radiation risks. Concentrations ...of these radionuclides (238U, 232Th, and 40K) have been measured on different igneous rocks, using a portable gamma-ray spectrometer at 450 points. Based on the obtained data, distribution maps of these radionuclides and the maps showing the absorbed dose rate in the air and radiogenic heat production (RHP) have been generated. We conclude that tephriphonolite and trachytes in potassic-ultrapotassic character display high radioactivity levels. On the other hand, it is revealed that the absorbed dose rate in the air ranging from 21 nGy/h to 482 nGy/h has been calculated as 8 times more than the world average (55 nGy/h). The results indicate that this region has crucial importance on human health and the environment. Therefore, the area requires special attention in terms of radiological hazards and further research should be done in the area regarding this issue.
•Radionuclide concentrations definition using the gamma-ray spectrometer in Gölcük volcano.•The comparison of radionuclide concentrations with geology.•The absorbed dose rate in the air has been calculated as 8 times more than the world average.•Radiological hazards on human health and the environment have been determined.
The recent use of prostate-specific membrane antigen as a biological target have improved the theragnostic approach to prostate and other types of cancer. Radiopharmaceuticals based on PSMA ...inhibitors radiolabeled with beta emitters as Lutetium-177 have demonstrated remarkable efficacy and safety, however, their clinical evaluation have also shown that therapeutic response of bone located metastases is poorer than that presented by soft tissue lesions. These observations conducted to the development and study at different levels of PSMA-targeting alpha-particle therapy exhibiting effective and promising antitumor activity. However, some aspects of the use of alpha emitters such as cellular dosimetry should be considered before applying them safely. The aim of the present work was to compare and calculate the absorbed dose of 177Lu-iPSMA and 225Ac-iPSMA using an animal bone metastasis model and experimental data obtained from cellular fractionation. The number of disintegrations and the dose factors for the theragnostic iPSMA pair, molecule that can be radiolabeled with 177Lu or 225Ac, were determined based on MIRD methodology, and used to calculate the absorbed dose to cell nucleus. A five times difference between 225Ac-iPSMA and 177Lu-iPSMA average dose rate to the tumor was calculated, being 2.3 ± 0.037 for the first and 0.5 ± 0.018 Gy for the second, both for each activity unit (MBq) administered.
•41% of the 225Ac-iPSMA taken up by LNCaP cells reached the nucleus.•225Ac-iPSMA specific and stably accumulates at bone metastasis.•Difference between 225Ac-iPSMA and 177Lu-iPSMA dose rate is of five times.
Fluorine 18-deoxyglucose is often used in Positron Emission Tomography devices. Positron Emission Tomography imaging is one of the useful tool which is used for cancer detection and its management. ...Positron Emission Tomography growth is limited due to problems that depend on the production of Fluorine-18. Imaging results are strongly depending on the information of nuclear reaction cross section data. This study is presented to calculate different quantities such as stopping power, CSDA range, simulated and distributed absorbed dose of Fluorine-18 in water. In order to access these goals, we use Geant4/Gate7 simulation and the Bethe-Bloch model. The results of this simulation and theoretical model presented are in good agreement with each other. The important point of this paper is the presentation of a theoretical approach in order to the production of Fluorine-18 using protons generated through the main D(d;p)Tand side 3 He(d;p)4 He nuclear fusion reaction in which uses Helium-3 is catalyzed.
252Cf neutron source has been widely used in biological effects of neutron radiation, neutron activation analysis and nuclear data acquisition. A seed irradiation device based on 252Cf fission ...neutron source was designed in this paper to study mutation breeding induced by neutron irradiation and biological effects of radiation. Based on the Monte Carlo method, neutron absorbed dose of pea seed samples in the designed irradiation region was simulated and calculated by MCNP. Results demonstrated that the relative standard deviation of the absorbed dose of pea seed samples in the three-layer partition is controlled lower than 10%, indicating the high dose uniformity in designed irradiation region. The experiment verified that the design of shield in this device meet the irradiation protection requirements.
Naturally occurring radionuclides, in particular, polonium-210 (210Po), have a greater contribution than anthropogenic radionuclides to the annual effective dose received by the general public due to ...consumption of seafood. Knowledge of potential trophic sources and transfer of 210Po to seabird species and subsequently to the Greenlandic people is, however, still poor. Here, we assess the transfer of 210Po and 210Pb to seabirds sampled during autumn and winter 2017 and 2018 in Greenland and provide a dose assessment. The activity concentrations of 210Po in muscle and liver, respectively, ranged from 0.2 ± 0.1 Bq kg−1 w.w. in glaucous gull (Larus hyperboreus) to 21.2 ± 22.6 Bq kg−1 w.w. in thick-billed murre (Uria lomvia) and from 32.0 ± 9.4 Bq kg−1 w.w. in common eider (Somateria mollissima) to 40.5 ± 49.0 Bq kg−1 w.w. in thick-billed murre. 210Po was non-uniformly distributed in the body of thick-billed murre. Kidneys and feathers showed higher 210Po activity concentrations than heart and bone. The 210Po/210Pb activity concentration ratios are higher than unity, indicating that 210Po is preferentially taken up by seabirds compared to its progenitor 210Pb. The derived annual absorbed dose from 210Po to the whole body of thick-billed murre was 6.4 × 102 ± 3.0 × 102 μGy. The annual effective dose to the average adult and representative person in Greenland due to ingestion of 210Po in seabirds was estimated to 13.0 μSv and 57.0 μSv, respectively. This derived dose is low and poses a slight risk, and risk communication is therefore deemed unnecessary.
Display omitted
•Large inter-specific variability of 210Po concentrations in seabirds.•Species feeding at lower trophic positions show higher 210Po concentrations than species feeding at high trophic positions.•210Po is non-uniformly distributed in the soft tissues and feathers of birds.•Derived annual absorbed dose due to 210Po to the whole body of thick-billed murre was low.•The annual effective dose due to ingestion of 210Po to average adult and representative person in Greenland is low.
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