Kidney Dose Research Articles

The effect of kidney volume estimation on dosimetry in lutetium-177 DOTATATE therapy.

The kidneys are the dose-limiting organ in lutetium-177 DOTATATE therapy. Therefore, it is advisable to perform critical organ dosimetry focussed on renal dose in treated patients. A key uncertainty in such dose estimates is the use of standard phantoms to represent the individual patient. The primary aim of this study was to investigate the accuracy of methods for estimating kidney size, and hence absorbed kidney dose, by comparison with individual measurements from computed tomography (CT) imaging. Kidney volume was measured using diagnostic CT images for 57 patients who underwent lutetium-177 DOTATATE therapy. Kidney mass was also estimated in two ways: using the standard adult phantoms, as well as through the application of a weight scaling factor to these phantoms and their organs. Dose calculations were performed for each of the three methods using OLINDA/EXM software. Scaling of the phantom by patient weight gave a more accurate result when compared with the CT gold standard than the standard phantom. The dose difference from the CT method had mean values of 1.4% (SD=22.6%) and 8.4% (SD=21.5%) for scaled and unscaled, respectively. Patient weight was not found to be a good predictor of kidney mass in these patients (r of 0.12 from linear regression analysis). The most accurate method of organ volume estimation would be individual measurements from CT imaging; however, where this is not possible, scaling of organ masses by weight ratio is more accurate than the use of the standard phantom.

Estimation of Kidney Dose for Pediatric Patients during X-Ray Examinations

Estimation of Kidney Dose for Pediatric Patients during X-Ray Examinations

Automated VMAT planning for postoperative adjuvant treatment of advanced gastric cancer

BackgroundPostoperative/adjuvant radiotherapy of advanced gastric cancer involves a large planning target volume (PTV) with multi-concave shapes which presents a challenge for volumetric modulated arc therapy (VMAT) planning. This study investigates the advantages of automated VMAT planning for this site compared to manual VMAT planning by expert planners.MethodsFor 20 gastric cancer patients in the postoperative/adjuvant setting, dual-arc VMAT plans were generated using fully automated multi-criterial treatment planning (autoVMAT), and compared to manually generated VMAT plans (manVMAT). Both automated and manual plans were created to deliver a median dose of 45 Gy to the PTV using identical planning and segmentation parameters. Plans were evaluated by two expert radiation oncologists for clinical acceptability. AutoVMAT and manVMAT plans were also compared based on dose-volume histogram (DVH) and predicted normal tissue complication probability (NTCP) analysis.ResultsBoth manVMAT and autoVMAT plans were considered clinically acceptable. Target coverage was similar (manVMAT: 96.6 ± 1.6%, autoVMAT: 97.4 ± 1.0%, p = 0.085). With autoVMAT, median kidney dose was reduced on average by > 25%; (for left kidney from 11.3 ± 2.1 Gy to 8.9 ± 3.5 Gy (p = 0.002); for right kidney from 9.2 ± 2.2 Gy to 6.1 ± 1.3 Gy (p < 0.001)). Median dose to the liver was lower as well (18.8 ± 2.3 Gy vs. 17.1 ± 3.6 Gy, p = 0.048). In addition, Dmax of the spinal cord was significantly reduced (38.3 ± 3.7 Gy vs. 31.6 ± 2.6 Gy, p < 0.001). Substantial improvements in dose conformity and integral dose were achieved with autoVMAT plans (4.2% and 9.1%, respectively; p < 0.001). Due to the better OAR sparing in the autoVMAT plans compared to manVMAT plans, the predicted NTCPs for the left and right kidney and the liver-PTV were significantly reduced by 11.3%, 12.8%, 7%, respectively (p ≤ 0.001). Delivery time and total number of monitor units were increased in autoVMAT plans (from 168 ± 19 s to 207 ± 26 s, p = 0.006) and (from 781 ± 168 MU to 1001 ± 134 MU, p = 0.003), respectively.ConclusionsFor postoperative/adjuvant radiotherapy of advanced gastric cancer, involving a complex target shape, automated VMAT planning is feasible and can substantially reduce the dose to the kidneys and the liver, without compromising the target dose delivery.

Technical Note: Single time point dose estimate for exponential clearance.

Although personalized dosimetry may be desirable for radionuclide therapy treatments, the multiple time samples required to determine the total integrated activity puts a burden on patients and clinic resources. The aim of this paper is to demonstrate that when some prior knowledge is known about the tracer kinetic parameters, the total integrated activity (and thus radiation dose) can be estimated from a single time sample. Mathematical derivations have been performed to generate equations for the total integrated activity in terms of a single time sample of activity for monoexponential and biexponential clearance. Simulations were performed using both exponential models where the rate constants and associated parameters were randomly sampled from distributions with a known mean. The actual total integrated activity for each random sample was compared with the estimated total integrated activity using the mean value of the parameters. Retrospective analysis of 90 Y DOTATOC data from a clinical trial provided a comparison of actual kidney dose with the estimated kidney dose using the single time point approach. The optimal sampling time for the single point approach was found to be equal to the mean time of the rate constant. The simulation results for the monoexponential and biexpoential models were similar. Regressions comparing the actual and estimated total integrated activity had very high correlations (r2 >0.95) along with acceptable standard errors of estimate, especially at the optimal sampling point. The retrospective analysis of the 90 Y DOTATOC data also yielded similar results with an r2 =0.95 and a standard error of estimate of 61cGy. In situations where there is prior knowledge about the population averages of kinetic parameters, these results suggest that the single time point approach can be used to estimate the total integrated activity and dose with sufficient accuracy to manage radionuclide therapy. This will make personalized dosimetry much easier to perform and more available to the community.

Dosimetry of conformal dynamic arc radiotherapy and intensity modulated radiotherapy in unresectable cholangiocarcinoma

Background: Radiotherapy in cholangiocrcinoma has to overcome organ tolerance of the upper abdomen. Hi-technology radiotherapy may improve conformity and reduce dose to those organ. Objective: Quantitatively compare the dosimetry of conformal dynamic arc radiotherapy (CD-arcRT) and intensity modulated radiotherapy (IMRT) in unresectable cholangiocarcinoma. Material and methods: Eleven cases of unresectable cholangiocarcinoma were re-planned with IMRT and CDarcRT at King Chulalongkhorn Memorial Hospital between 20 September 2004 and 31 December 2005. Both the planning techniques were evaluated using the dose volume histogram of the planning target volume and organ at risk. The conformation number and dose to critical normal structures were used to determine the techniques. Results: IMRT technique was significantly conformed to the planning target volume than CD-arcRT in term of conformation number. For critical structure, IMRT significantly reduced the radiation dose to liver in terms of mean liver dose, V30Gy and V20Gy of the right kidney. Conclusion: The advantage of IMRT was more conformity and reduced dose to critical structure compared with CD-arcRT, but there was no difference between these techniques in terms of V20Gy of left kidney and maximum dose to the spinal cord.

Estimating the Patient-specific Dose to the Thyroid and Breasts and Overall Risk in Chest CT When Using Organ-based Tube Current Modulation.

Purpose To assess the potential dose reduction to the thyroid and breasts in chest computed tomography (CT) with organ-based tube current modulation (OBTCM). Materials and Methods In this retrospective study (from January 2015 to December 2016), the location of the breasts with respect to the reduced tube current zone was determined. With Monte Carlo simulations, patient-specific dose distributions of chest CT scans were calculated for 50 female patients (mean age, 53.7 years ± 17.5; range, 20-80 years). The potential dose reduction with OBTCM was assessed. In addition, simulations of clinical OBTCM scans were made for 17 of the 50 female patients (mean age, 43.8 years ± 17.1; range, 20-69 years). Posterior organs in the field of view were analyzed and lifetime attributable risk (LAR) of cancer incidence and mortality was estimated. Image quality between standard CT and OBTCM scans was compared. Results No women had all breast tissue within the reduced tube current zone. Dose reductions of 18% in the thyroid and 9% in the breasts were observed, whereas the doses in lung, liver, and kidney were 17%, 11%, and 26% higher. Overall, the LAR for cancer incidence was not significantly different between conventional and OBTCM scanning (P = .06). Image quality improved with OBTCM (P < .002). Conclusion The potential benefit of OBTCM to the female breast in chest CT is overestimated because of a limited reduced tube current zone; despite a 9% dose reduction to the female breast, posterior organs will absorb up to 26% more radiation, resulting in no reduction in radiation-induced malignancies. © RSNA, 2018.

Dosimetric Analysis of Unflattened (FFFB) and Flattened (FB) Photon Beam Energy for Gastric Cancers Using IMRT and VMAT—a Comparative Study

To evaluate the feasibility of flattening filter free beam (FFFB) for the treatment of gastric tumors and to review their benefits over 6MV flatten beam (6MV_FFB). Fifteen patients with histologically proven gastric carcinoma were selected. CT scans with slice thickness of 0.3cm were acquired and planning target volume (PTV) and organ at risk (OAR) were delineated. Plans were made retrospectively for each patient for the prescription dose of 45Gy/25 fractions to the PTV. Four isocentric plans were compared in the present study on Varian TrueBeam linear accelerator (Varian Medical Systems, Palo Alto, CA, USA). PTV D98% was 44.41 ± 0.12, 44.38 ± 0.13, 44.59 ± 0.14, and 44.49 ± 0.19Gy for IMRT 6MV_FFB, IMRT 6MV_FFFB, VMAT 6MV_FFB, and VMAT 6MV_FFFB respectively. 6MV_FFFB beam minimizes the mean heart dose Dmean (P = 0.001). VMAT dominates over IMRT when it came to kidney doses V12Gy (P = 0.02), V23Gy (P = 0.015), V28Gy (P = 0.011), and Dmax (P < 0.01). VMAT has significantly reduced the doses to kidneys. It was analyzed that 6MV_FFFB significantly reduces the dose to normal tissues (P = 0.006 and P = 0.018). VMAT significantly reduces the TMU, which is required to deliver the similar dose by IMRT (P < 0.01). Unflattened beam spares the organs at risk significantly to avoid the chances of secondary malignancies and reduces the intra-fraction motion during treatment due to provision of higher dose rate. Hence, we conclude that 6MV unflattened beam can be used to treat gastric carcinoma.

Kinetics and dosimetric predictors of acute radiation-induced lymphopenia in pancreatic cancer.

300 Background: Radiation (RT) induced lymphopenia (RIL) is an adverse prognostic factor in pancreatic cancer (PC) and is likely due to the irradiation of lymphocytes in the RT field. The goal of this study was to identify dosimetric predictors for high rates of absolute lymphocyte count (ALC) loss during RT for PC. Methods: This was a retrospective study of 34 PC patients in an institutional database who had received concurrent 5-FU or gemcitabine-based chemoradiation (50-54 Gy) and had ≥ 3 ALCs measured during RT. Baseline ALC was normal (&gt;1000 cells/uL) in 28/34 (82%) and grade 3-4 RIL occurred in 24/34 (71%). ALC was plotted against fraction # and a best-fit line for each patient was created to determine per-fraction loss in ALC (PFLAC). Linear regression was used to correlate PFLAC with dosimetric parameters including mean dose to gut, liver, kidney, spleen, and cisterna chyli, as well as estimated dose to immune cells (EDIC), which calculates dose to immune cells according to the % of body lymphocytes contained in each organ. Results: All patients exhibited exponential loss in ALC during RT. Mean PFLAC was 6.8% (range 1.7-13.4); fraction # was strongly correlated with ALC (mean R2 = 0.89). Patients with &gt;/= grade 3 lymphopenia had a significantly higher PFLAC than those with grade 0 - 2 lymphopenia (mean daily loss 7.8% in Gr 3-4 vs. 4.8% in Gr 0-2, p = 0.001; independent sample T test). Field size was not correlated with PFLAC for high (&gt; 1 Gy) or low (&lt; 0.5 Gy) isodose volumes. Mean whole body (r = 0.59, p &lt; 0.001), bowel (r = 0.39, p = 0.012), liver (r = 0.42, p = 0.007), and cisterna chyli (r = 0.583, p = 0.004) doses were moderately correlated with PFLAC; mean kidney (r = 0.22, p = 0.11) and spleen (r = 0.26, p = 0.06) doses were weakly correlated with PFLAC. EDIC was more strongly correlated with PFLAC than any individual organ mean dose (r = 0.69, p &lt; 0.001). Conclusions: Patients undergoing RT for PC experience a predictable RIL characterized by an exponential loss of lymphocytes per day. PFLAC is a useful method of characterizing RIL and facilitates evaluation of dosimetric predictors of RIL. We identified dose to cisterna chyli as a significant contributor to RIL in PC; however, EDIC has a stronger correlation with RIL severity than any single organ dose.

Relevant tumor sink effect in prostate cancer patients receiving 177Lu-PSMA-617 radioligand therapy.

In metastatic prostate cancer patients PSMA targeting radioligands have gained significant impact as theranostic probes. In this study a correlation between total tumor volume (TTV) and measured kidney dose as well as salivary glands (SG) uptake in 177Lu-PSMA-617 therapy was evaluated. Eleven consecutive prostate cancer patients receiving a first cylcle of 177Lu-PSMA-617 (administered activity of approximately 6GBq) were included. The 68Ga-PSMA-11 PET/CT scan previous to therapy was used to determine TTV and SG uptake (glandulae submandibularis) employing PMOD version 3.403 with different 68Ga-PSMA-11 thresholds based on the standardized uptake value (SUV).The kidney dose was estimated with the software ULMDOS using planar whole-body scintigrams. Kidney dose and SG uptake was inversely correlated to TTV, indicating high kidney dose and high SG uptake in case of low tumor load and low kidney dose and low SG uptake in case of high tumor load. Our data support the hypothesis that in 177Lu-PSMA-617 therapy an individualized treatment activity based on total tumor volume could be beneficiary.

Dosimetry of 175Ytterbium-poly (amidoamine) Therapy for Humans' Organs.

Purpose:This investigation focuses on biodistribution of irradiated dendrimer encapsulated ytterbium-175 (175Yb) and to estimate the absorbed dose from intravenous injection of PAMAM encapsulated 175Yb to human organs.Methods:A dendrimer compound containing an average of 55 Yb+3 ions per dendrimer was prepared and irradiated with neutrons for 2h at 3×1011 n.cm-2s-1 neutron flux. The resulting mixture was injected into a group of tumor bearing mice and the mice were excised, weighed and counted at certain times to study the biodistribution. The human organs absorbed dose was assessed by MIRD schema and MCNP simulation.Results:The specific activity and radiochemical purity of the irradiated nano-composite were 7MBq/mg and >99% respectively. The rapid up take of dendrimer was in liver, lung, and, spleen. MIRD and MCNPX were applied for dose estimation. The human absorbed dose in liver, lung, spleen, kidney and bone that simulated by MCNP are 1.266, 0.8081, 0.8347, 0.03979 and 0.01706 mGy/MBq respectively and these values for MIRD schema are 1.351, 0.73, 1.03, 0.039, and 0.0097 mGy/MBq respectively.Conclusion:The results showed that 175Yb-PAMAM nano-radiopharmaceutical has potential of application for liver and lung tumors.

A knowledge-based approach to automated planning for hepatocellular carcinoma.

PurposeTo build a knowledge‐based model of liver cancer for Auto‐Planning, a function in Pinnacle, which is used as an automated inverse intensity modulated radiation therapy (IMRT) planning system.Methods and MaterialsFifty Tomotherapy patients were enrolled to extract the dose–volume histograms (DVHs) information and construct the protocol for Auto‐Planning model. Twenty more patients were chosen additionally to test the model. Manual planning and automatic planning were performed blindly for all twenty test patients with the same machine and treatment planning system. The dose distributions of target and organs at risks (OARs), along with the working time for planning, were evaluated.ResultsStatistically significant results showed that automated plans performed better in target conformity index (CI) while mean target dose was 0.5 Gy higher than manual plans. The differences between target homogeneity indexes (HI) of the two methods were not statistically significant. Additionally, the doses of normal liver, left kidney, and small bowel were significantly reduced with automated plan. Particularly, mean dose and V15 of normal liver were 1.4 Gy and 40.5 cc lower with automated plans respectively. Mean doses of left kidney and small bowel were reduced with automated plans by 1.2 Gy and 2.1 Gy respectively. In contrast, working time was also significantly reduced with automated planning.ConclusionsAuto‐Planning shows availability and effectiveness in our knowledge‐based model for liver cancer.

Software-assisted dosimetry in peptide receptor radionuclide therapy with 177Lutetium-DOTATATE for various imaging scenarios.

In peptide receptor radionuclide therapy (PRRT) of patients with neuroendocrine neoplasias (NENs), intratherapeutic dosimetry is mandatory for organs at risk (e.g. kidneys) and tumours. We evaluated commercial dosimetry software (Dosimetry Toolkit) using varying imaging scenarios, based on planar and/or tomographic data, regarding the differences in calculated organ/tumour doses and the use for clinical routines. A total of 16 consecutive patients with NENs treated by PRRT with 177Lu-DOTATATE were retrospectively analysed. Single-photon emission computed tomography (SPECT)/low-dose computed tomography (CT) of the thorax and abdomen and whole body (WB) scintigraphy were acquired up to 7 days p.i. (at a maximum of five imaging time points). Different dosimetric scenarios were evaluated: (1) a multi-SPECT-CT scenario using SPECT/CT only; (2) a planar scenario using WB scintigraphy only; and (3) a hybrid scenario using WB scintigraphy in combination with a single SPECT/low-dose CT. Absorbed doses for the kidneys, liver, spleen, lungs, bladder wall and tumours were calculated and compared for the three different scenarios. The mean absorbed dose for the kidneys estimated by the multi-SPECT-CT, the planar and the hybrid scenario was 0.5 ± 0.2 Sv GBq-1, 0.8 ± 0.4 Sv GBq-1 and 0.6 ± 0.3 Sv GBq-1, respectively. The absorbed dose for the residual organs was estimated higher by the planar scenario compared to the multi-SPECT-CT or hybrid scenario. The mean absorbed tumour doses were 2.6 ± 1.5 Gy GBq-1 for the multi-SPECT-CT, 3.1 ± 2.2 Gy GBq-1 for the hybrid scenario and 5.3 ± 6.3 Gy GBq-1 for the planar scenario. SPECT-based dosimetry methods determined significantly lower kidney doses than the WB scintigraphy-based method. Dosimetry based completely on SPECT data is time-consuming and tedious. Approaches combining SPECT/CT and WB scintigraphy have the potential to ensure compromise between accuracy and user-friendliness.

Physiological and immune response of juvenile rainbow trout to dietary bovine lactoferrin

Lactoferrin, a large multifunctional glycoprotein, is involved in many physiological functions but its immunomodulatory pathways are not well characterized in fish. The objective of the present study was to investigate the temporal effect of dietary bovine lactoferrin (BLf) at low (0.1%) and high (1%) on immunological organs of rainbow trout juveniles. BLf diets did not affect specific growth rate, haematocrit, splenic index, spleen respiratory burst activity as well as humoral (mIgM) and neutrophils (MPO) gene expressions after short term - 35 days (D35) and long term nutrient test - 51 days (D51) of feeding. Both low and high BLf doses induced enhanced level of plasma alternative complement activity, plasma total immunoglobulin on D35 and D51, lymphocyte plus thrombocyte cell proportion on D35 and monocyte cell proportion in total blood leukocyte cells on D51. On D51 but not on D35, BLf diets upregulated the expression of inflammatory genes in kidney for il-1 at the low BLf dose, il-8 at both BLf doses and il-6 at the high BLf dose in spleen, and il-10 at both BLf doses in kidney. Moreover, the expression of T helper (cd4-2α; cd4-2β) genes was significantly upregulated only on D51 by both BLf doses in both spleen and kidney tissues. On D51, controls and BLf treated fish were intraperitoneally injected with A. salmonicida achromogenes. The expression of 13 immune genes was evaluated at 44 h post-injection (D54). The expression of lysozyme gene was upregulated by both BLf doses after bacterial infection both in spleen and kidney. The expression of mcsfrα (spleen) and tgf-β1 (kidney) was also modulated by both BLf doses. Low and high BLf doses enhanced disease resistance of rainbow trout juveniles with the cumulative survival rate of 36% and 38% respectively while those of the control was 19% after 14 days challenged with bacteria. The results indicate that BLf diets activated the humoral immunity, associated to blood leukocyte cells of rainbow trout after short term BLf administration, and the long term BLf administration was necessary for sensitizing other lymphoid organs such as in spleen and kidney. Only after long term test, BLf diets induced significantly higher levels of innate and adaptive immune gene expressions than those of the control. Dietary BLf activated more markedly the expression of innate immune genes than the adaptive ones; this upregulation of some immune genes could explain the high disease resistance observed in rainbow trout juveniles fed BLf.

8-Aminoguanosine Exerts Diuretic, Natriuretic, and Glucosuric Activity via Conversion to 8-Aminoguanine, Yet Has Direct Antikaliuretic Effects.

8-Aminoguanosine induces diuresis, natriuresis, glucosuria, and antikaliuresis. These effects could be mediated via 8-aminoguanosine's metabolism to 8-aminoguanine. In this study, we tested this hypothesis in anesthetized rats. First, we demonstrated that at 55- to 85-minutes post-i.v. administration, 8-aminoguanosine and 8-aminoguanine (33.5 µmol/kg) significantly increased urine volume [ml/30 min: 8-aminoguanosine from 0.3 ± 0.1 to 0.9 ± 0.1 (mean ± S.E.M.; n = 7); 8-aminoguanine from 0.3 ± 0.1 to 1.5 ± 0.2 (n = 8)], sodium excretion (µmol/30 min: 8-aminoguanosine from 12 ± 5 to 109 ± 21; 8-aminoguanine from 18 ± 8 to 216 ± 31), and glucose excretion (µg/30 min: 8-aminoguanosine from 18 ± 3 to 159 ± 41; 8-aminoguanine from 17 ± 3 to 298 ± 65). Both compounds significantly decreased potassium excretion (µmol/30 min: 8-aminoguanosine from 62 ± 7 to 39 ± 9; 8-aminoguanine from 61 ± 10 to 34 ± 6). Next, we administered 8-aminoguanosine and 8-aminoguanine i.v. (33.5 µmol/kg) and measured renal interstitial (microdialysis probes) 8-aminoguanosine and 8-aminoguanine. The i.v. administration of 8-aminoguanosine and 8-aminoguanine similarly increased renal medullary interstitial levels of 8-aminoguanine [nanograms per milliliter; 8-aminoguanosine from 4 ± 1 to 1025 ± 393 (n = 6), and 8-aminoguanine from 2 ± 1 to 1069 ± 407 (n = 6)]. Finally, we determine the diuretic, natriuretic, glucosuric, and antikaliuretic effects of intrarenal artery infusions of 8-aminoguanosine and 8-aminoguanine (0.1, 0.3, and 1 µmol/kg/min). 8-Aminoguanine increased urine volume and sodium and glucose excretion by the ipsilateral kidney, yet had only mild effects at the highest dose in the contralateral kidney. Intrarenal infusions of 8-aminoguanosine did not induce diuresis, natriuresis, or glucosuria in either the ipsilateral or contralateral kidney, yet decreased potassium excretion in the ipsilateral kidney. Together these data confirm that the diuretic, natriuretic, and glucosuric effects of 8-aminoguanosine are not direct, but require metabolism to 8-aminoguanine. However, 8-aminoguanosine has direct antikaliuretic effects.

Quantitative Single-Photon Emission Computed Tomography/Computed Tomography for Glomerular Filtration Rate Measurement.

We propose a quantitative Tc-99m diethylenetriaminepentaacetic acid (DTPA) single-photon emission computed tomography/computed tomography (SPECT/CT) for glomerular filtration rate (GFR) measurement. Quantitative SPECT/CT data obtained at 2-3min post-Tc-99m DTPA injection (370MBq) were used to determine % injected doses (%IDs) for individual kidneys. The reproducibility of %ID measurement was tested and compared with planar scintigraphy. Cr-51 ethylenediaminetetraacetic acid (EDTA) GFR was used as reference standard. Nine young volunteers, representing normal GFR, and ten older volunteers, reflecting impaired GFR, were enrolled. The established GFR equation derived from these volunteers was applied to 19 renal tumor patients post-partial nephrectomy. At 2-3 min, %ID was most reproducible with the highest intraclass correlation (ICC) (0.9379) and lowest % coefficient of variation (CV) (6.5259%), which were more reliable than the ICC (0.9368) and %CV (6.7689%) of planar scintigraphy. Cr-51 EDTA GFR (93.16±24.81ml/min) correlated significantly with %ID (7.66±2.15%, r=0.7906, p=0.0001), yielding an equation: Cr-51 EDTA GFR (ml/min)=(%ID×9.1462)+23.0653. This equation revealed significant decreases in total and nephrectomized kidney GFR (p=0.0012 and p<0.0001, respectively) from preoperative to 3-month postoperative measurements. Quantitative Tc-99m DTPA SPECT/CT produces reliable and clinically applicable %ID estimates that translate to the GFR of individual kidneys.

Estimating patient dose from CT exams that use automatic exposure control: Development and validation of methods to accurately estimate tube current values.

The vast majority of body CT exams are performed with automatic exposure control (AEC), which adapts the mean tube current to the patient size and modulates the tube current either angularly, longitudinally or both. However, most radiation dose estimation tools are based on fixed tube current scans. Accurate estimates of patient dose from AEC scans require knowledge of the tube current values, which is usually unavailable. The purpose of this work was to develop and validate methods to accurately estimate the tube current values prescribed by one manufacturer's AEC system to enable accurate estimates of patient dose. Methods were developed that took into account available patient attenuation information, user selected image quality reference parameters and x-ray system limits to estimate tube current values for patient scans. Methods consistent with AAPM Report 220 were developed that used patient attenuation data that were: (a) supplied by the manufacturer in the CT localizer radiograph and (b) based on a simulated CT localizer radiograph derived from image data. For comparison, actual tube current values were extracted from the projection data of each patient. Validation of each approach was based on data collected from 40 pediatric and adult patients who received clinically indicated chest (n = 20) and abdomen/pelvis (n = 20) scans on a 64 slice multidetector row CT (Sensation 64, Siemens Healthcare, Forchheim, Germany). For each patient dataset, the following were collected with Institutional Review Board (IRB) approval: (a) projection data containing actual tube current values at each projection view, (b) CT localizer radiograph (topogram) and (c) reconstructed image data. Tube current values were estimated based on the actual topogram (actual-topo) as well as the simulated topogram based on image data (sim-topo). Each of these was compared to the actual tube current values from the patient scan. In addition, to assess the accuracy of each method in estimating patient organ doses, Monte Carlo simulations were performed by creating voxelized models of each patient, identifying key organs and incorporating tube current values into the simulations to estimate dose to the lungs and breasts (females only) for chest scans and the liver, kidney, and spleen for abdomen/pelvis scans. Organ doses from simulations using the actual tube current values were compared to those using each of the estimated tube current values (actual-topo and sim-topo). When compared to the actual tube current values, the average error for tube current values estimated from the actual topogram (actual-topo) and simulated topogram (sim-topo) was 3.9% and 5.8% respectively. For Monte Carlo simulations of chest CT exams using the actual tube current values and estimated tube current values (based on the actual-topo and sim-topo methods), the average differences for lung and breast doses ranged from 3.4% to 6.6%. For abdomen/pelvis exams, the average differences for liver, kidney, and spleen doses ranged from 4.2% to 5.3%. Strong agreement between organ doses estimated using actual and estimated tube current values provides validation of both methods for estimating tube current values based on data provided in the topogram or simulated from image data.

A Short-Term Biological Indicator for Long-Term Kidney Damage after Radionuclide Therapy in Mice.

Folate receptor (FR)-targeted radionuclide therapy using folate radioconjugates is of interest due to the expression of the FR in a variety of tumor types. The high renal accumulation of radiofolates presents, however, a risk of radionephropathy. A potential option to address this challenge would be to use radioprotectants, such as amifostine. Methods for early detection of kidney damage that—in this case—cannot be predicted based on dose estimations, would facilitate the development of novel therapies. The aim of this study was, therefore, to assess potentially changing levels of plasma and urine biomarkers and to determine DNA damage at an early stage after radiofolate application. The identification of an early indicator for renal damage in mice would be useful since histological changes become apparent only several months after treatment. Mice were injected with different quantities of 177Lu-folate (10 MBq, 20 MBq and 30 MBq), resulting in mean absorbed kidney doses of ~23 Gy, ~46 Gy and ~69 Gy, respectively, followed by euthanasia two weeks (>85% of the mean renal radiation dose absorbed) or three months later. Whereas all investigated biomarkers remained unchanged, the number of γ-H2AX-positive nuclei in the renal cortex showed an evident dose-dependent increase as compared to control values two weeks after treatment. Comparison with the extent of kidney injury determined by histological changes five to eight months after administration of the same 177Lu-folate activities suggested that the quantitative assessment of double-strand breaks can be used as a biological indicator for long-term radiation effects in the kidneys. This method may, thus, enable faster assessment of radiopharmaceuticals and protective measures by preventing logistically challenging long-term investigations to detect kidney damage.

Estimation of kidneys and urinary bladder doses based on the region of interest in 18fluorine-fluorodeoxyglucose positron emission tomography/computed tomography examination: a preliminary study

Kidneys and urinary bladder are common physiologic uptake sites of 18fluorine-fluorodeoxyglucose (18F-FDG) causing increased exposure of low energy ionizing radiation to these organs. Accurate measurement of organ dose is vital as 18F-FDG is directly exposed to the organs. Organ dose from 18F-FDG PET is calculated according to the injected 18F-FDG activity with the application of dose coefficients established by International Commission on Radiological Protection (ICRP). But this dose calculation technique is not directly measured from these organs; rather it is calculated based on total injected activity of radiotracer prior to scanning. This study estimated the 18F-FDG dose to the kidneys and urinary bladder in whole body positron emission tomography/computed tomography (PET/CT) examination by comparing dose from total injected activity of 18F-FDG (calculated dose) and dose from organs activity based on the region of interest (ROI) (measured dose). Nine subjects were injected intravenously with the mean 18F-FDG dose of 292.42 MBq prior to whole body PET/CT scanning. Kidneys and urinary bladder doses were estimated by using two approaches which are the total injected activity of 18F-FDG and organs activity concentration of 18F-FDG based on drawn ROI with the application of recommended dose coefficients for 18F-FDG described in the ICRP 80 and ICRP 106. The mean percentage difference between calculated dose and measured dose ranged from 98.95% to 99.29% for the kidneys based on ICRP 80 and 98.96% to 99.32% based on ICRP 106. Whilst, the mean percentage difference between calculated dose and measured dose was 97.08% and 97.27% for urinary bladder based on ICRP 80 while 96.99% and 97.28% based on ICRP 106. Whereas, the range of mean percentage difference between calculated and measured organ doses derived from ICRP 106 and ICRP 80 for kidney doses were from 17.00% to 40.00% and for urinary bladder dose was 18.46% to 18.75%. There is a significant difference between calculated dose and measured dose. The use of organ activity estimation based on drawn ROI and the latest version of ICRP 106 dose coefficient should be explored deeper to obtain accurate radiation dose to patients.

Lu-177 DOTATATE dosimetry for neuroendocrine tumor: single center experience

Lu-177 labelled with DOTATE is widely acceptable to treat Neuroendocrine Tumor (NET) disease and it better improvement of quality of patients’ life since few years ago. However, the radionuclide toxicity becomes the main limitation of the (NET) treatment. Therefore, we performed a pilot study aimed to estimate radiation absorbed doses to dose-limiting organs to develop a systemic therapy with Lu-177 in NET patients. In this study, five set of planar whole body images was acquired every 0.5 hour, 4 hours, 24 hours, 48 hours and 72 hours after Lu-177 administrations. The planar image acquisition was done using Philip Brightview X with Medium Energy General Purpose Collimator (MEGP) collimator. All patients’ images in Conjugate View (CV) format were transferred into PMOD 3.7 Software for Region of Interest (ROI) analysis. The ROI were drawn at selected organs such as kidneys, liver, spleen and bladder. This study found that the mean absorbed dose for kidneys 0.62 ± 0.26 Gy/GBq, liver 0.63 ± 0.28 Gy/GBq, spleen 0.83 ± 0.73 Gy/GBq and bladder 0.14 ± 0.07 Gy/GBq. The radionuclide kinetic for the whole body 99.7 ± 0.1 percent at 0.5 hours, 79.5 ± 10.7 percent at 4 hours, 56.6 ± 10.3 percent at 24 hours, 43.2 ± 7.9 percent at 48 hours and 37.1 ± 9.0 percent at 72 hours. This study verifies that this planar quantitative method able to determine organ at risk and the result line with other published data.

Dosimetry software Hermes Internal Radiation Dosimetry: from quantitative image reconstruction to voxel-level absorbed dose distribution.

The aim of this work is to validate a software package called Hermes Internal Radiation Dosimetry (HIRD) for internal dose assessment tailored for clinical practice. The software includes all the necessary steps to perform voxel-level absorbed dose calculations including quantitative reconstruction, image coregistration and volume of interest tools. The basics of voxel-level dosimetry methods and implementations to HIRD software are reviewed. Then, HIRD is validated using simulated SPECT/CT data and data from Lu-DOTATATE-treated patients by comparing absorbed kidney doses with OLINDA/EXM-based dosimetry. In addition, electron and photon dose components are studied separately in an example patient case. The simulation study showed that HIRD can reproduce time-activity curves accurately and produce absorbed doses with less than 10% error for the kidneys, liver and spleen. From the patient data, the absorbed kidney doses calculated using HIRD and using OLINDA/EXM were highly correlated (Pearson's correlation coefficient, r=0.98). From Bland-Altman plot analysis, an average absorbed dose difference of -2% was found between the methods. In addition, we found that in Lu-DOTATATE-treated patients, photons can contribute over 10% of the kidney's total dose and is partly because of cross-irradiation from high-uptake lesions close to the kidneys. HIRD is a straightforward voxel-level internal dosimetry software. Its clinical utility was verified with simulated and clinical Lu-DOTATATE-treated patient data. Patient studies also showed that photon contribution towards the total dose can be relatively high and voxel-level dose calculations can be valuable in cases where the target organ is in close proximity to high-uptake organs.