Table 1 - uploaded by Michael Lassmann
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Source publication
The radiation absorbed dose to blood and organs from activity in the blood is relevant for nuclear medicine dosimetry and for research in biodosimetry. The present study provides coefficients for the average absorbed dose rates to the blood from blood-borne activity for radionuclides frequently used in targeted radiotherapy and in PET diagnostics....
Citations
... In patients 3, 4, and 5, additional blood samples were collected after [ 177 Lu]Lu-DOTA-EB-TATE at the time of the scans to determine the absorbed doses to the blood per administered activity from the activity concentrations in whole blood. Blood dose was determined from the time integrated activity coefficients calculated as time integral of a bi-exponential fit function to the blood measurements with the S-value for selfirradiation of blood of 1.72·10 −11 Gy·ml/(Bq·s) [13]. SUV peak standardised uptake value in the 1 mL spherical volume with the highest activity uptake in somatostatin receptor directed positron emission tomography; GFR glomerular filtration rate Tables 2 and 3 from unity were tested with the Student two-sided one-sample T test using JASP [14]. ...
Purpose
The radiolabelled somatostatin analogue [¹⁷⁷Lu]Lu-DOTA-EB-TATE binds to albumin via Evans blue, thereby increasing the residence time in the blood and potentially allowing more therapeutic agent to be absorbed into the target tissue during peptide receptor radionuclide therapy. It was tested in selected patients whether the substance is superior to [¹⁷⁷Lu]Lu-DOTA-TOC.
Methods
Activity kinetics in organs and tumours after [¹⁷⁷Lu]Lu-DOTA-EB-TATE and [¹⁷⁷Lu]Lu-DOTA-TOC were compared intraindividually in five patients with progressive somatostatin receptor-positive disease scheduled for radionuclide therapy.
Results
In comparison to [¹⁷⁷Lu]Lu-DOTA-TOC, tumour doses per administered activity were higher for [¹⁷⁷Lu]Lu-DOTA-EB-TATE in 4 of 5 patients (median ratio: 1.7; range: 0.9 to 3.9), kidney doses (median ratio: 3.2; range: 1.6 to 9.8) as well as spleen doses (median ratio: 4.7; range 1.2 to 6.2) in all patients, and liver doses in 3 of 4 evaluable patients (median ratio: 4.0; range: 0.7 to 4.9). The tumour to critical organs absorbed dose ratios were higher after [¹⁷⁷Lu]Lu-DOTA-TOC in 4 of 5 patients.
Conclusions
Prior to a treatment with [¹⁷⁷Lu]Lu-DOTA-EB-TATE, it should be assessed individually whether the compound is superior to established substances.
... It is possible that this observation is a result of using a minimal administered activity for pediatric patients below a certain weight. This would increase the blood concentration with decreasing weight and is consistent with circulating blood as the main source of FDG activity in normal tissue [25]. Table 5 lists the fitted parameter values for Eq. 1 used to fit these data. ...
Background:
Absorbed dose estimates for pediatric patients require pharmacokinetics that are, to the extent possible, age-specific. Such age-specific pharmacokinetic data are lacking for many of the diagnostic agents typically used in pediatric imaging. We have developed a pharmacokinetic model of [(18)F]fluorodeoxyglucose (FDG) applicable to premature infants and to 0- (newborns) to 5-year-old patients, which may be used to generate model-derived time-integrated activity coefficients and absorbed dose calculations for these patients.
Methods:
The FDG compartmental model developed by Hays and Segall for adults was fitted to published data from infants and also to a retrospective data set collected at the Boston Children's Hospital (BCH). The BCH data set was also used to examine the relationship between uptake of FDG in different organs and patient weight or age.
Results:
Substantial changes in the structure of the FDG model were required to fit the pediatric data. Fitted rate constants and fractional blood volumes were reduced relative to the adult values.
Conclusions:
The pharmacokinetic models developed differ substantially from adult pharmacokinetic (PK) models which can have considerable impact on the dosimetric models for pediatric patients. This approach may be used as a model for estimating dosimetry in children from other radiopharmaceuticals.
... The observed numbers of RIF per cell for the first hours after treatment obtained in this work are in good agreement with the in vitro calibration curve [27] developed in our laboratory. The slight differences in slope in relation to the in vitro calibration curve can be explained by the results of two recent studies by Hänscheid et al. [51,52] in which the authors investigated the absorbed doses to the blood from compounds that do not bind to the blood. According to these results [51] the gamma component is underestimated for 177 Lu by a factor of about 2 as compared to the model we assumed. ...
... According to these results [51] the gamma component is underestimated for 177 Lu by a factor of about 2 as compared to the model we assumed. In addition, when a realistic distribution of vessel sizes is taken into account this results in a beta absorbed dose that is lower than the maximum energy deposited by beta particles [52]. A specific model for the case of PRRT describing the absorbed dose to the blood is so far not available. ...
The aim of the study was to investigate DNA double strand break (DSB) formation and its correlation with the absorbed dose to the blood lymphocytes of patients undergoing their first peptide receptor radionuclide therapy (PRRT) with (177)Lu-labelled DOTATATE/DOTATOC.
The study group comprised 16 patients receiving their first PRRT. At least six peripheral blood samples were obtained before, and between 0.5 h and 48 h after radionuclide administration. From the time-activity curves of the blood and the whole body, residence times for blood self-irradiation and whole-body irradiation were determined. Peripheral blood lymphocytes were isolated, fixed with ethanol and subjected to immunofluorescence staining for colocalizing γ-H2AX/53BP1 DSB-marking foci. The average number of DSB foci per cell per patient sample was determined as a function of the absorbed dose to the blood and compared with an in vitro calibration curve established in our laboratory with (131)I and (177)Lu.
The average number of radiation-induced foci (RIF) per cell increased over the first 5 h after radionuclide administration and decreased thereafter. A linear fit from 0 to 5 h as a function of the absorbed dose to the blood agreed with our in vitro calibration curve. At later time-points the number of RIF decreased, indicating progression of DNA repair.
Measurements of RIF and the absorbed dose to the blood after systemic administration of (177)Lu may be used to obtain data on the individual dose-response relationships in vivo. Individual patient data were characterized by a linear dose-dependent increase and an exponential decay function describing repair.
Rationale: To build a refined dosimetry model for [177Lu]Lu-DOTA-[Tyr3]octreotate (177Lu-DOTATATE) in vivo experiments enabling the correlation of absorbed dose with double strand breaks (DSBs) induction and cell death. Methods: Somatostatin receptor type-2 (SSTR2) expression of NCI-H69 xenografted mice, injected with 177Lu-DOTATATE, was imaged at 0, 2, 5, 11 days. This was used as input to reconstruct realistic 3 dimensional heterogeneous activity distributions and tissue geometries of both cancer and heathy cells. The resulting volumetric absorbed dose rate distributions were calculated using GATE Monte Carlo code and compared to homogenous dose rate distributions. The absorbed dose (0-2 days) on µm-scale sections was correlated with DSBs induction, measured by γH2AX foci. Moreover, the absorbed dose on larger mm-scale sections delivered over the whole treatment (0-14 days) was correlated to the modelled in vivo survival to determine the radiosensitivity parameters α and β for comparison with experimental data (cell death assay, volume response) and external beam radiotherapy (EBRT). The DNA-damage repair half-life Tμ and proliferation doubling time TD were obtained by fitting the DSBs and tumor volume data over time. Results: A linear correlation with a slope of 0.0223 DSBs/cell mGy-1 between the absorbed dose and the number of DSBs/cell has been established. The heterogeneous dose distributions differ significantly from the homogenous dose distributions, with their corresponding average S-values diverging at 11 days up to +58%. No significant difference between modelled in vivo survival is observed in the first 5 days when using heterogeneous and uniform dose distributions, respectively. The radiosensitivity parameter analysis for the in vivo survival correlation indicates that the minimal effective dose rates for cell kill are 13.72 mGy/h and 7.40 mGy/h, with α=0.14 Gy-1 and 0.264 Gy-1, respectively and α/β=100 Gy; decreasing the α/β leads to a decrease in the minimal effective dose rate for cell kill. Within the linear quadratic (LQ) model, the best matching in vivo survival correlation (α=0.1 Gy-1, α/β=100 Gy, Tµ=60 h, TD=14.5 d) indicates a relative biological effectiveness value of 0.4 in comparison to EBRT. Conclusion: Our results demonstrate that accurate dosimetric modelling is crucial to establish dose-response correlations enabling optimization of treatment protocols.
