Renal Dosimetry Research Articles

Single-Time-Point Renal Dosimetry Using Nonlinear Mixed-Effects Modeling and Population-Based Model Selection in [177Lu]Lu-PSMA-617 Therapy.

The aim of this study was to investigate the accuracy of single-time-point (STP) renal dosimetry imaging using SPECT/CT data, a nonlinear mixed-effects (NLME) model, and a population-based model selection (PBMS) in a large population for 177Lu-labeled prostate-specific membrane antigen therapy. Methods: Biokinetic data (mean ± SD) of [177Lu]Lu-PSMA-617 in kidneys at time points 1 (1.8 ± 0.8 h), 2 (18.7 ± 0.9 h), 3 (42.6 ± 1.0 h), 4 (66.3 ± 0.9 h), and 5 (160.3 ± 24.2 h) after injection were obtained from 63 patients with metastatic castration-resistant prostate cancer using SPECT/CT. Thirteen functions were derived from various parameterizations of 1- to 5-exponential functions. The function's parameters were fitted in the NLME framework to the all-time-point (ATP) data. The PBMS NLME method was performed using the goodness-of-fit test and Akaike weight to select the best function fitting the data. The best function from ATP fitting was used to calculate the reference time-integrated activity and absorbed doses. In STP dosimetry, the parameters of a particular patient with STP data were fitted simultaneously to the STP data at different time points of that patient with ATP data of all other patients. The parameters from STP fitting were used to calculate the STP time-integrated activity and absorbed doses. Relative deviations (RDs) and root-mean-square errors (RMSEs) were used to analyze the accuracy of the calculated STP absorbed dose compared with the reference absorbed dose obtained from the best-fit ATP function. The performance of STP dosimetry using PBMS NLME modeling was compared with the Hänscheid and Madsen methods. Results: The function [Formula: see text] was selected as the best-fit ATP function, with an Akaike weight of 100%. For STP dosimetry, the STP measurement by SPECT/CT at time point 3 (42.6 ± 1.0 h) showed a relatively low mean RD of -4.4% ± 9.4% and median RD of -0.7%. Time point 3 had the lowest RMSE value compared with those at the other 4 time points. The RMSEs of the absorbed dose RDs for time points 1-5 were 23%, 16%, 10%, 20%, and 53%, respectively. The STP dosimetry using the PBMS NLME method outperformed the Hänscheid and Madsen methods for all investigated time points. Conclusion: Our results show that a single measurement of SPECT/CT at 2 d after injection might be used to calculate accurate kidney-absorbed doses using the NLME method and PBMS.

Phase II trial demonstrates the efficacy and safety of individualized, dosimetry-based 177Lu-DOTATATE treatment of NET patients

PurposeRadionuclide therapy with 177Lu-DOTATATE is well established for patients with advanced somatostatin receptor–positive neuroendocrine tumors with a standard schedule of 7.4 GBq at four occasions. However, this approach does not consider individual variability affecting the tumor radiation dose or dose to organs at risk. Therefore, it is important to assess more personalized strategies. The aim of this phase II trial was to evaluate individualized 177Lu-DOTATATE for which the number of cycles varied based on renal dosimetry.MethodsPatients were eligible if they had a progressive, somatostatin receptor–positive neuroendocrine tumor with a Ki 67 labeling index < 20%. They received cycles of 7.4 GBq of 177Lu-DOTATATE at 10 ± 2-week intervals until a predefined radiation dose to the kidneys was reached. The primary endpoint was objective tumor response (RECIST v 1.1). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity (CTCAE v. 4.0).ResultsNinety-six patients who had received a median of 5 cycles (range 1–9) were evaluable for efficacy. The objective tumor response was 16% partial response, 66% stable disease, and 19% progressive disease. The median PFS and OS were 29 months and 47 months, respectively, and were significantly associated with kidney dose, performance status, and Ki 67 levels but not with tumor origin. The overall toxicity was mild, and the most common events were grade 1–2 anemia, thrombocytopenia, fatigue, nausea, and diarrhea. Grade 3–4 toxicity occurred in < 10% of patients and was mostly hematological, with no grade 3–4 renal toxicity.ConclusionIndividualized treatment with 177Lu-DOTATATE based on renal dosimetry is clearly feasible with low toxicity and promising efficacy, showing the potential to further improve outcome beyond the standard approach, and should be further assessed in randomized trials.Trial registrationEudraCT 2011–000,240-16. NCT01456078. https://clinicaltrials.gov/ct2/show/NCT01456078

Simplified patient-specific renal dosimetry in 177Lu therapy: a proof of concept.

The aim of this proof-of-concept study is to propose a simplified personalized kidney dosimetry procedure in 177Lu peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors and metastatic prostate cancer. It relies on a single quantitative SPECT/CT acquisition and multiple radiometric measurements executed with a collimated external probe, properly directed on kidneys. We conducted a phantom study involving external count-rate measurements in an abdominal phantom setup filled with activity concentrations of 99mTc, reproducing patient-relevant organ effective half-lives occurring in 177Lu PRRT. GATE Monte Carlo (MC) simulations of the experiment, using 99mTc and 177Lu as sources, were performed. Furthermore, we tested this method via MC on a clinical case of 177Lu-DOTATATE PRRT with SPECT/CT images at three time points (2, 20 and 70 hrs), comparing a simplified kidney dosimetry, employing a single SPECT/CT and probe measurements at three time points, with the complete MC dosimetry. The experimentally estimated kidney half-life with background subtraction applied was compatible within 3% with the expected value. The MC simulations of the phantom study, both with 99mTc and 177Lu, confirmed a similar level of accuracy. Concerning the clinical case, the simplified dosimetric method led to a kidney dose estimation compatible with the complete MC dosimetry within 6%, 12% and 2%, using respectively the SPECT/CT at 2, 20 and 70hrs. The proposed simplified procedure provided a satisfactory accuracy and would reduce the imaging required to derive the kidney absorbed dose to a unique quantitative SPECT/CT, with consequent benefits in terms of clinic workflows and patient comfort.

Tissue dose estimation after extravasation of 177Lu-DOTATATE

BackgroundExtravasation of radiopharmaceuticals used for vectorized internal radiotherapy can lead to severe tissue damage (van der Pol et al., Eur J Nucl Med Mol Imaging 44:1234–1243, 2017). Clinical management of these extravasations requires the preliminary estimation of the dose distribution in the extravasation area. Data are scarce regarding the dose estimation in the literature. This work presents a methodology for estimating the dose distribution after an extravasation occurred in September 2017, in the arm of a patient during a 7.4-GBq infusion of Lutathera ® (AAA).MethodsA local quantification procedure initially developed for renal dosimetry was used. A calibration factor was determined and verified by phantom study. Extravasation volume of interest and its variation in time were determined using 4 whole body (WB) planar acquisitions performed at 2 h (T2h), 5 h (T5h), 20 h (T20h), and 26 h (T26h) after the beginning of the infusion and three SPECT/CT thoracic acquisitions at T5h, T20h, and T26h. For better estimation of initial extravasation volume, 3 volumes were defined on SPECT images using a 3D activity threshold. Cumulated activities and associated absorbed doses (D1, D2, D3) were calculated in the 3 volumes using the MIRD formalism.ResultsVolumes estimated using 3D threshold were V1 = 1000 mL, V2 =400 mL, and V3 =180 mL. Cumulated activities were evaluated using a monoexponential fit on activities calculated on SPECT images. Estimated local absorbed doses in V1, V2, and V3 were D1 = 2.3 Gy, D2 = 4.1 Gy, and D3 = 6.8 Gy. Evolution in time of local activity in the extravasation area was consistent with an effective local half-life (Teff) of 2.3 h.ConclusionsRapid local dose estimation was permitted thanks to knowledge of the calibration factor determined previous to accidental extravasation. Lutathera® lymphatic drainage was quick in the arm (Teff = 2.3h). Estimated doses were in the lower range of deterministic effects and far under soft tissue necrosis threshold. Thus, no surgical rinse was proposed. The patient did not show any clinical consequence of the extravasation.

Dosimétrie rénale du 177Lu-Dotatate : mise en place au sein du Groupement hospitalier Est des Hospices Civils de Lyon

IntroductionThe kidney is considered as a critical dose-limiting organ with 177Lu-Dotatate. Renal dosimetry could play a role in optimizing treatment. We present a feedback on the implementation of renal dosimetry in our medical center. Material and methodThe renal dosimetry of the 1st administration of 177Lu-Dotatate (approximately 7.4 GBq) has been performed for seven patients. The reference dosimetry strategy included 4 post-therapeutic SPECT/CT at 6h, 24h, 72h and 168h and anatomical renal volume delineation (VOI). Alternative dosimetric strategies consisted of 72h or 168h time point eviction (time sampling A or B) and delimitation of 1 or 3 spherical VOIs (3mL each) per kidney (“1 sVOI” or “3 sVOI” methods). The quantitative scintigraphic processing was performed by 4 operators using Dosimetry Toolkit®. The renal dose was calculated with OLINDA/EXM® 2.0. ResultsThe calculated mean absorbed renal dose was 3.68±0.68Gy with the reference method, with no significant impact of interoperator variability (P=0.41). It was in satisfactory agreement with time sampling A or B. The “1 sVOI” and “3 sVOI” methods overestimated the renal dose (5.01±0.94Gy and 4.91±0.79Gy respectively), with a significant impact on interoperator variability (P<0.05), despite a reduction in processing time. ConclusionThe main logistic constraint of 177Lu-Dotatate renal dosimetry in our center is the time-consumption due to SPECT/CT acquisitions. A possible approach supported by our preliminary results is a reduction in the number of scintigraphic acquisitions.

Technical Note: Optimal sampling schedules for kidney dosimetry based on the hybrid planar/SPECT method in 177 Lu-PSMA therapy.

Accurate and precise renal dosimetry during 177 Lu-labeled prostate-specific membrane antigen (PSMA) radioligand therapy is crucial for therapy decisions. Sampling schedules for estimating the necessary time-integrated activity coefficients (TIACs) are not optimized and standardized for clinical practice. Therefore, a simulation study to determine optimal sampling schedules (OSSs) was performed on 13 virtual 177 Lu-PSMA I&T therapy patients. A total of 880 clinically feasible sampling schedules for planar imaging (three time points) were investigated. To simulate the hybrid planar/SPECT method, an additional quantitative SPECT/CT measurement following one planar image was considered. For each sampling schedule and patient, the activity values were generated separately. Measurement noise was modeled by drawing random numbers of log-normal distributions. The used fractional standard deviations (FSD) differed depending on the imaging modality. For activity values assigned to planar imaging, systematic noise between 25% and 75% of the total noise was simulated. After fitting with a mono-exponential function, the root-mean-squared errors of the deviations of the simulated TIACs from the ground truth for 1000 replications were used to determine the OSS. The uncertainties of the TIACs and renal dose coefficients were estimated. For the hybrid planar/SPECT method, OSSs were determined to be (3-4, 72-76, 124-144) h post injection (p.i.) with the quantitative SPECT/CT scan shortly after the second measurement. The accuracy and precision of the determined TIACs were in the range of (-3.0± 6.2)% and (-1.0 ± 6.5)%. This precision was improved by a factor 2-3 compared to dosimetry based on planar images only. Similar results were obtained for the renal dose coefficients. The virtual patients' renal dose coefficients were (0.68 ±0.24) Gy/GBq indicating that a population-based method yields an uncertainty of 35%. Dosimetry based on the hybrid planar/SPECT method with OSS outperforms dosimetry based on planar images. The high variability in dose coefficients between the virtual patients demonstrates the need for individualized dosimetry.

Feasibility and accuracy of single time point imaging for renal dosimetry following 177Lu-DOTATATE (\u2018Lutate\u2019) therapy

BackgroundThis study aims to assess both feasibility and accuracy of renal dosimetry imaging protocols in patients receiving Lutate therapy for neuroendocrine tumours (NETs), when data acquisition over multiple days is not possible on all cycles.MethodPatients who had received a full 4 cycles of Lutate therapy with complete imaging at each cycle were included. Imaging consisted of quantitative SPECT/CT of the kidneys at 4, 24 and 96–120 h post injection. Renal absorbed dose was calculated for each data set, and in addition, five alternative methods were explored for comparison. Method 1: a patient average clearance time (t1/2 average) derived from the first half of contributing patient data was used to estimate absorbed dose for subsequent patients based on 4 h imaging alone; method 2: t1/2 average was applied to subsequent patients on 24 h imaging alone; method 3: a patient-specific clearance rate (t1/2 patient) was determined from complete image data of cycle 1 and applied subsequently to remaining cycles using 4 h image data alone; method 4: t1/2 patient was applied to 24 h imaging alone in subsequent cycles; method 5: the 120 h data was estimated on subsequent cycles based on the cycle 1 fraction of injected activity (%IA) at 24 and 120 h.ResultsTwenty treatments from 18 patients, resulting in 80 cycles of therapy, were analysed. The measured average renal absorbed dose per cycle of treatment was 0.38 ± 0.19 Gy/GBq when derived from full imaging data. The use of t1/2 average applied to a single time point led to large deviations of dose estimates from true values (on average 59% and 30%, when using 4 h data and 24 h data, respectively). The use of complete image data on cycle 1 and the derivation of t1/2 patient led to improved dose estimates, with an average deviation from true values of 13% and 2% when using 4 h data only and 24 h data only, respectively. The use of a 120 h %IA derived from cycle 1 led to an average deviation from true dose estimates of 14%.ConclusionIn instances where demands on both patients and facilities make multiple time point data acquisition impractical, renal dosimetry is best derived through complete imaging at cycle 1 only followed by a single 24 h imaging time point on subsequent cycles, assuming no significant changes in renal function during the time course of therapy.

58 Dose estimation for an extravasation in a patient treated with [formula omitted]Lu-DOTATATE

Introduction Extravasation of radiopharmaceuticals used for therapy purpose, such as Lu-177 ( E β Max = 498 keV, E γ = 113 keV (6%) and 208 keV (10%), T = 6.6 days) can lead to severe tissue damage [1] . In September 2017, an extravasation occurred in the arm of a patient during a 7.4 GBq perfusion of lutathera ® (AAA). Methods Four whole body (WB) acquisitions were performed at 2 h, 5 h, 20 h and 26 h after the beginning of the perfusion (H0). Three SPECT/CT were performed following the WB acquisitions at 5 h, 20 h and 26 h. Images were acquired with a Symbia T2® camera (Siemens Healthcare) with a MELP collimator, a main window around 208 keV, 20 cm/min for the WB acquisition and 2x30 projections of 30s for the SPECT acquisition. A local quantification procedure developed for renal dosimetry and based on a calibration factor was used, with the following parameters: FLASH 3D®, 10 iterations, 10 subsets, CT-based attenuation correction, scatter correction and 4 mm FWHM Gaussian filtering. Effective period was determined on the geometric mean of whole body images. Given the complexity of subcutaneous tissue contouring, 3 volumes (V1 = 180, V2 = 400 et V3 = 1000 mL) were defined on SPECT images using a 3D threshold. Cumulated activities and associated doses (D1, D2, D3) were calculated in the 3 volumes using a conversion factor ξ = 0.0024 mGy.g/(MBq.s), from the website RADAR [2] . Results Estimated effective periods were 11 h in the whole body and 3 h in the arm. As SPECT images at H0 + 2 h were not available, activity at H0 + 2 h was evaluated using estimated activity from SPECT images at H0 + 5 h and a ratio of the number of counts in a ROI around the arm on geometric mean of WB images at H0 + 2 h and at H0 + 5 h. Cumulated activities were evaluated using a mono exponential fit on activities calculated on SPECT images. Estimated doses in V1, V2 and V3 were D1 = 7.8 Gy, D2 = 5.4 Gy and D3 = 2.8 Gy. Conclusions Estimated doses values are in the range of deterministic effects. However, the patient did not show any clinical sign of the irradiation. Elimination of the product was quick in the arm (Teff = 3 h) and was promoted by specific interventions (warming, repeated massages around the injection site).

Accuracy and reproducibility of simplified QSPECT dosimetry for personalized 177Lu-octreotate PRRT

BackgroundRoutine dosimetry is essential for personalized 177Lu-octreotate peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NETs), but practical and robust dosimetry methods are needed for wide clinical adoption. The aim of this study was to assess the accuracy and inter-observer reproducibility of simplified dosimetry protocols based on quantitative single-photon emission computed tomography (QSPECT) with a limited number of scanning time points. We also updated our personalized injected activity (IA) prescription scheme.MethodsSeventy-nine NET patients receiving 177Lu-octreotate therapy (with a total of 279 therapy cycles) were included in our study. Three-time-point (3TP; days 0, 1, and 3) QSPECT scanning was performed following each therapy administration. Dosimetry was obtained using small volumes of interest activity concentration sampling for the kidney, the bone marrow and the tumor having the most intense uptake. Accuracy of the simplified dosimetry based on two-time-point (2TP; days 1 and 3, monoexponential fit) or a single-time-point (1TPD3; day 3) scanning was assessed, as well as that of hybrid methods based on 2TP for the first cycle and 1TP (day 1 or 3; 2TP/1TPD1 and 2TP/1TPD3, respectively) or no imaging at all (based on IA only; 2TP/no imaging (NI)) for the subsequent induction cycles. The inter-observer agreement was evaluated for the 3TP, 2TP, and hybrid 2TP/1TPD3 methods using a subset of 60 induction cycles (15 patients). The estimated glomerular filtration rate (eGFR), body size descriptors (weight, body surface area (BSA), lean body weight (LBW)), and products of both were assessed for their ability to predict IA per renal absorbed dose at the first cycle.ResultsThe 2TP dosimetry estimates correlated highly with those from the 3TP data for all tissues (Spearman r > 0.99, P < 0.0001) with small relative errors between the methods, particularly for the kidney and the tumor, with median relative errors not exceeding 2% and interdecile ranges spanning over less than 6% and 4%, respectively, for the per-cycle and cumulative estimates. For the bone marrow, the errors were slightly greater (median errors < 6%, interdecile ranges < 14%). Overall, the strength of correlations of the absorbed dose estimates from the simplified methods with those from the 3TP scans tended to progressively decrease, and the relative errors to increase, in the following order: 2TP, 2TP/1TPD3, 1TPD3, 2TP/1TPD1, and 2TP/NI. For the tumor, the 2TP/NI scenario was highly inaccurate due to the interference of the therapeutic response. There was an excellent inter-observer agreement between the three observers, in particular for the renal absorbed dose estimated using the 3TP and 2TP methods, with mean errors lesser than 1% and standard deviations of 5% or lower. The eGFR · LBW and eGFR · BSA products best predicted the ratio of IA to the renal dose (GBq/Gy) for the first cycle (Spearman r = 0.41 and 0.39, respectively; P < 0.001). For the first cycle, the personalized IA proportional to eGFR · LBW or eGFR · BSA decreased the range of delivered renal absorbed dose between patients as compared with the fixed IA. For the subsequent cycles, the optimal personalized IA could be determined based on the prior cycle renal GBq/Gy with an error of less than 21% in 90% of patients.ConclusionsA simplified dosimetry protocol based on two-time-point QSPECT scanning on days 1 and 3 post-PRRT provides reproducible and more accurate dose estimates than the techniques relying on a single time point for non-initial or all cycles and results in limited patient inconvenience as compared to protocols involving scanning at later time points. Renal absorbed dose over the 4-cycle induction PRRT course can be standardized by personalizing IA based on the product of eGFR with LBW or BSA for the first cycle and on prior renal dosimetry for the subsequent cycles.

Feasibility of simplifying renal dosimetry in 177Lu peptide receptor radionuclide therapy

BackgroundRecently, 177Lu-dotatate therapy for neuroendocrine tumours has received regulatory approval. Dosimetry can be used to optimize treatment on an individual basis, but there is no international consensus as to how it should be done.The aim of this study is to determine a feasible and accurate dosimetry method to guide individualized peptide receptor radionuclide therapy (PRRT) for patients with neuroendocrine tumours.As part of a clinical trial on 177Lu-dotatate therapy, renal dosimetry was performed for all patients in each treatment cycle, using a hybrid planar-SPECT/CT method. In the present study, we use the image data acquired from 22 patients and 119 cycles and define a set of alternative treatment planning strategies, each representing a simplification in terms of image acquisition and dosimetric calculations. The results from the simplified strategies are compared to the results from the protocol-prescribed hybrid planar-SPECT/CT-based method by analysing differences both in per-cycle and total cumulative absorbed dose (AD) analyses.ResultsIn general, the SPECT-based methods gave results that were largely consistent with the protocol-specified hybrid method, both in the per-cycle and cumulative AD analyses. Notably, performing one SPECT/CT per cycle at 96 h yielded ADs that were very similar to the protocol method. The methods using planar dosimetry resulted in larger variations, as expected, while giving 4 cycles to all patients resulted in the largest inter-individual differences in cumulative AD.ConclusionsPerforming one SPECT/CT at 96 h in every treatment cycle gives sufficiently reliable dosimetric results to base individualized treatment planning on, with a reasonable demand on resources.

Personalized 177Lu-octreotate peptide receptor radionuclide therapy of neuroendocrine tumours: a simulation study.

Peptide receptor radionuclide therapy (PRRT) with 177Lu-octreotate is commonly administered at empiric, fixed amounts of injected radioactivity (IA). This results in highly variable absorbed doses to critical organs and suboptimal treatment of most patients. The primary aims of this study were to design a personalized PRRT (P-PRRT) protocol based on dosimetry, and to perform a simulation of this protocol in a retrospective cohort of patients with neuroendocrine tumours, in order to assess the potential of P-PRRT to safely increase the absorbed dose to the tumour during a four-cycle induction course. Thirty-six patients underwent 122 fixed-IA 177Lu-octreotate PRRT cycles with quantitative SPECT/CT-based dosimetry. Twenty-two patients completed a four-cycle induction course (29.6 ± 2.4GBq cumulative IA), with kidney, bone marrow and maximum tumour absorbed doses of 16.2 ± 5.5, 1.3 ± 0.8, and 114 ± 66Gy, respectively. We simulated a P-PRRT regime in which the renal absorbed dose per IA was predicted by the body surface area and glomerular filtration rate for the first cycle, and by renal dosimetry of the previous cycle(s) for the following cycles. Personalized IA was adjusted at each cycle in order to reach the prescribed renal absorbed dose of 23Gy over four cycles (with a 25-50% reduction when renal or bone marrow function was impaired). Simulated IA and absorbed doses were based on actual patient characteristics, laboratory values and absorbed doses per IA delivered at each cycle. In the P-PRRT regime, cumulative IA could have been increased to 43.7 ± 16.5GBq over four induction cycles (10.9 ± 5.0GBq per cycle), yielding cumulative kidney, bone marrow and maximum tumour absorbed doses of 21.5 ± 2.5, 1.63 ± 0.61, and 163.4 ± 85.9Gy, respectively. This resulted in an average 1.48-fold increase in cumulative maximum tumour absorbed dose over empiric PRRT (range, 0.68-2.64-fold; P = 0.0013). By standardizing the renal absorbed dose delivered during the induction course, P-PRRT has the potential to significantly increase tumour absorbed dose, thus to augment the therapeutic benefit while limiting toxicity.

Individualised 177Lu-DOTATATE treatment of neuroendocrine tumours based on kidney dosimetry

PurposeTo present data from an interim analysis of a Phase II trial designed to determine the feasibility, safety, and efficacy of individualising treatment based on renal dosimetry, by giving as many cycles as possible within a maximum renal biologically effective dose (BED).MethodTreatment was given with repeated cycles of 7.4 GBq 177Lu-DOTATATE at 8-12-week intervals. Detailed dosimetry was performed in all patients after each cycle using a hybrid method (SPECT + planar imaging). All patients received treatment up to a renal BED of 27 ± 2 Gy (α/β = 2.6 Gy) (Step 1). Selected patients were offered further treatment up to a renal BED of 40 ± 2 Gy (Step 2). Renal function was followed by estimation and measurement of the glomerular filtration rate (GFR).ResultsFifty-one patients were included in the present analysis. Among the patients who received treatment as planned, the median number of cycles in Step 1 was 5 (range 3-7), and for those who completed Step 2 it was 7 (range 5-8); 73% were able to receive >4 cycles. Although GFR decreased in most patients after the completion of treatment, no grade 3-4 toxicity was observed. Patients with a reduced baseline GFR seemed to have an increased risk of GFR decline. Five patients received treatment in Step 2, none of whom exhibited a significant reduction in renal function.ConclusionsIndividualising PRRT using renal dosimetry seems feasible and safe and leads to an increased number of cycles in the majority of patients. The trial will continue as planned.

Design and Fabrication of Kidney Phantoms for Internal Radiation Dosimetry Using 3D Printing Technology

A set of 4 single-compartment kidney phantoms with filling volumes between 8 and 123 mL was designed on the basis of the outer kidney dimensions provided by MIRD pamphlet 19. After the phantoms had been printed, SPECT/CT acquisitions of 3 radionuclides (99mTc, 177Lu, and 131I) were obtained and calibration constants determined for each radionuclide-volume combination. A set of additionally manufactured spheres matching the kidney volumes was also examined to assess the influence of phantom shape and size on the calibration constants. A set of refillable, waterproof, and chemically stable kidneys and spheres was successfully manufactured. Average calibration factors for 99mTc, 177Lu, and 131I were obtained in a large source measured in air. For the largest phantom (122.9 mL), the volumes of interest had to be enlarged by 1.2 mm for 99mTc, 2.5 mm for 177Lu, and 4.9 mm for 131I in all directions to obtain calibration factors comparable to the reference. Although partial-volume effects were observed for decreasing phantom volumes (percentage difference of up to 9.8% for the smallest volume [8.6 mL]), the difference between corresponding sphere-kidney pairs was small (<1.1% for all volumes). 3D printing is a promising prototyping technique for geometry-specific calibration of SPECT/CT systems. Although the underlying radionuclide and the related collimator have a major influence on the calibration, no relevant differences between kidney-shaped and spherically shaped uniform-activity phantoms were observed. With comparably low costs and submillimeter resolution, 3D printing techniques hold the potential for manufacturing individualized anthropomorphic phantoms in many clinical applications in nuclear medicine.

Renal function affects absorbed dose to the kidneys and haematological toxicity during ¹⁷⁷Lu-DOTATATE treatment.

PurposePeptide receptor radionuclide therapy (PRRT) has become an important treatment option in the management of advanced neuroendocrine tumours. Long-lasting responses are reported for a majority of treated patients, with good tolerability and a favourable impact on quality of life. The treatment is usually limited by the cumulative absorbed dose to the kidneys, where the radiopharmaceutical is reabsorbed and retained, or by evident haematological toxicity. The aim of this study was to evaluate how renal function affects (1) absorbed dose to the kidneys, and (2) the development of haematological toxicity during PRRT treatment.MethodsThe study included 51 patients with an advanced neuroendocrine tumour who received 177Lu-DOTATATE treatment during 2006 – 2011 at Sahlgrenska University Hospital in Gothenburg. An average activity of 7.5 GBq (3.5 – 8.2 GBq) was given at intervals of 6 – 8 weeks on one to five occasions. Patient baseline characteristics according to renal and bone marrow function, tumour burden and medical history including prior treatment were recorded. Renal and bone marrow function were then monitored during treatment. Renal dosimetry was performed according to the conjugate view method, and the residence time for the radiopharmaceutical in the whole body was calculated.ResultsA significant correlation between inferior renal function before treatment and higher received renal absorbed dose per administered activity was found (p < 0.01). Patients with inferior renal function also experienced a higher grade of haematological toxicity during treatment (p = 0.01). The residence time of 177Lu in the whole body (range 0.89 – 3.0 days) was correlated with grade of haematological toxicity (p = 0.04) but not with renal absorbed dose (p = 0.53).ConclusionPatients with inferior renal function were exposed to higher renal absorbed dose per administered activity and developed a higher grade of haematological toxicity during 177Lu-DOTATATE treatment. The study confirms the tolerability of PRRT in patients with an advanced neuroendocrine tumour but indicates that patients with inferior renal function are at risk of being exposed to higher absorbed doses to normal tissue on treatment.

Sci—Thur AM: YIS ‐ 03: irtGPUMCD: a new GPU‐calculated dosimetry code for 177Lu‐octreotate radionuclide therapy of neuroendocrine tumors

In peptide receptor radionuclide therapy (PRRT), huge inter‐patient variability in absorbed radiation doses per administered activity mandates the utilization of individualized dosimetry to evaluate therapeutic efficacy and toxicity. We created a reliable GPU‐calculated dosimetry code (irtGPUMCD) and assessed 177Lu‐octreotate renal dosimetry in eight patients (4 cycles of approximately 7.4 GBq).irtGPUMCD was derived from a brachytherapy dosimetry code (bGPUMCD), which was adapted to 177Lu PRRT dosimetry. Serial quantitative single‐photon emission computed tomography (SPECT) images were obtained from three SPECT/CT acquisitions performed at 4, 24 and 72 hours after 177Lu‐octreotate administration, and registered with non‐rigid deformation of CT volumes, to obtain 177Lu‐octreotate 4D quantitative biodistribution. Local energy deposition from the β disintegrations was assumed. Using Monte Carlo gamma photon transportation, irtGPUMCD computed dose rate at each time point. Average kidney absorbed dose was obtained from 1‐cm3 VOI dose rate samples on each cortex, subjected to a biexponential curve fit. Integration of the latter time‐dose rate curve yielded the renal absorbed dose.The mean renal dose per administered activity was 0.48 ± 0.13 Gy/GBq (range: 0.30–0.71 Gy/GBq). Comparison to another PRRT dosimetry code (VRAK: Voxelized Registration and Kinetics) showed fair accordance with irtGPUMCD (11.4 ± 6.8 %, range: 3.3–26.2%). These results suggest the possibility to use the irtGPUMCD code in order to personalize administered activity in PRRT. This could allow improving clinical outcomes by maximizing per‐cycle tumor doses, without exceeding the tolerable renal dose.

Proton versus photon radiation therapy for patients with high‐risk neuroblastoma: The need for a customized approach

Proton therapy for treatment for high-risk neuroblastoma may offer sparing of organs at risk (OAR) when compared to intensity-modulated X-ray therapy (IMXT). Double-scattered proton plans and IMXT plans delivering 2,160 cGy to the primary tumor site and other residual disease were developed for 13 consecutive HR-NBL patients. Radiation doses to target volumes and OAR were calculated to determine the optimal modality for each. All patients received radiation (5/13 ≥ 2 sites). No patient has experienced local recurrence or clinical organ toxicity. Coverage was excellent using both protons and IMXT: median % dose delivered to 95% clinical target volume was 99% and 100%, respectively. For nine patients with lateralized disease, proton therapy offered sparing of the contralateral kidney both with regard to median dose and dose to 20% (median <1 cGy vs. 362 cGy, P = 0.01; median 100 cGy vs. 634 cGy, P = 0.02, respectively). Proton therapy did not reduce ipsilateral kidney dose, and for 2 select patients with lateralized disease IMXT improved overall bilateral renal sparing. Proton therapy improved median bowel (median 33 cGy vs. 590 cGy, P = 0.01), total body (median <1 cGy vs. 30 cGy, P = 0.15), and liver dose (median <1 cGy vs. 529, P < 0.001). When chest RT was required, proton therapy decreased median heart dose and mean lung dose. For most patients (11/13), proton therapy offered the optimal combination of target coverage and organ sparing, and is a feasible treatment for HR-NBL. We recommend a customized approach with careful evaluation of renal dosimetry; IMXT may be preferred for select patients.

Significant impact of transient deterioration of renal function on dosimetry in PRRT

Peptide receptor radionuclide therapy (PRRT), with (90)Y-DOTATOC and (177)Lu-DOTATATE as most clinically used radiopeptides, is widely used in the management of metastatic neuroendocrine tumors. With respect to radiation dosimetry, the kidneys are the critical organ for (90)Y-DOTATOC. Renal irradiation is significant because of reabsorption of the radiopeptide from the proximal tubuli and the resulting retention in the interstitium, mainly in the inner cortical zone. The high energy and consequently wide range in tissue of the yttrium-90 beta particle result in high absorbed doses to the kidney cortex and medulla. Accurate renal dosimetry can help minimizing radiation nephropathy. We report a case of a 69-year-old candidate for PRRT with an acceptable kidney function at the time of screening. When performing (111)In-octreotide pretreatment dosimetry 3 weeks later, we observed a drastic deterioration in kidney function, caused by undisclosed non-steroidal anti-inflammatory drug intake. The calculated kidney biological effective dose (BED) was 153 Gy after four projected cycles. PRRT was canceled as our full-course BED limit is 37 Gy and the patient was switched to morphine analgesics. Renal function normalized after 3 months and repeated dosimetry yielded an acceptable kidney BED of 28 Gy after four projected cycles (7 Gy/cycle). This case emphasizes that acute kidney insufficiency can yield toxic kidney doses in a single therapy cycle, with an inherent risk of persistent renal insufficiency. All clinical factors which might influence kidney function should be verified at screening and before PRRT administration.

Renal Dosimetry: Ready for BED? Response to the Italian Researchers

Cancer Biotherapy & RadiopharmaceuticalsVol. 26, No. 1 Letter to the EditorRenal Dosimetry: Ready for BED? Response to the Italian ResearchersJeffry A. Siegel, Michael G. Stabin, and Robert M. SharkeyJeffry A. SiegelNuclear Physics Enterprises, Marlton, New Jersey.Search for more papers by this author, Michael G. StabinVanderbilt University School of Medicine, Nashville, Tennessee.Search for more papers by this author, and Robert M. SharkeyCMMI/Garden State Cancer Center, Belleville, New Jersey.Search for more papers by this authorPublished Online:28 Feb 2011https://doi.org/10.1089/cbr.2010.0920AboutSectionsView articleView Full TextPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Renal Dosimetry: Ready for BED? Response to the Italian Researchers." , 26(1), pp. 141–142FiguresReferencesRelatedDetails Volume 26Issue 1Feb 2011 InformationCopyright 2011, Mary Ann Liebert, Inc.To cite this article:Jeffry A. Siegel, Michael G. Stabin, and Robert M. Sharkey.Renal Dosimetry: Ready for BED? Response to the Italian Researchers.Cancer Biotherapy and Radiopharmaceuticals.Feb 2011.141-142.http://doi.org/10.1089/cbr.2010.0920Published in Volume: 26 Issue 1: February 28, 2011Online Ahead of Print:February 24, 2011PDF download

Renal Dosimetry: Ready for Biological Equivalent Dose? Response to Medical Internal Radiation Dose and European Association of Nuclear Medicine Committee Letters

Cancer Biotherapy & RadiopharmaceuticalsVol. 25, No. 6 Letters to the EditorRenal Dosimetry: Ready for Biological Equivalent Dose? Response to Medical Internal Radiation Dose and European Association of Nuclear Medicine Committee LettersJeffry A. Siegel, Michael G. Stabin, and Robert M. SharkeyJeffry A. SiegelNuclear Physics Enterprises, Marlton, New Jersey.Search for more papers by this author, Michael G. StabinVanderbilt University School of Medicine, Nashville, Tennessee.Search for more papers by this author, and Robert M. SharkeyCMMI/Garden State Cancer Center, Belleville, New Jersey.Search for more papers by this authorPublished Online:5 Jan 2011https://doi.org/10.1089/cbr.2010.0878AboutSectionsView articleView Full TextPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetailsCited bySensitivity Analysis of a Physiologically Based Pharmacokinetic Model Used for Treatment Planning in Peptide Receptor Radionuclide Therapy Deni Hardiansyah, Nusrat Jihan Begum, Peter Kletting, Felix M. Mottaghy, and Gerhard Glatting22 July 2016 | Cancer Biotherapy & Radiopharmaceuticals, Vol. 31, No. 6Individualized Dosimetry of Kidney and Bone Marrow in Patients Undergoing 177 Lu-DOTA-Octreotate Treatment7 December 2012 | Journal of Nuclear Medicine, Vol. 54, No. 1 Volume 25Issue 6Dec 2010 InformationCopyright 2010, Mary Ann Liebert, Inc.To cite this article:Jeffry A. Siegel, Michael G. Stabin, and Robert M. Sharkey.Renal Dosimetry: Ready for Biological Equivalent Dose? Response to Medical Internal Radiation Dose and European Association of Nuclear Medicine Committee Letters.Cancer Biotherapy and Radiopharmaceuticals.Dec 2010.763-765.http://doi.org/10.1089/cbr.2010.0878Published in Volume: 25 Issue 6: January 5, 2011PDF download

Something More than Estimating Renal Dosimetry

Cancer Biotherapy & RadiopharmaceuticalsVol. 25, No. 6 Letters to the EditorSomething More than Estimating Renal DosimetryLisa Bodei, Marta Cremonesi, and Giovanni PaganelliLisa BodeiDepartment of Nuclear Medicine, European Institute of Oncology, Milano, Italy.Search for more papers by this author, Marta CremonesiDepartment of Medical Physics, European Institute of Oncology, Milano, Italy.Search for more papers by this author, and Giovanni PaganelliDepartment of Nuclear Medicine, European Institute of Oncology, Milano, Italy.Search for more papers by this authorPublished Online:5 Jan 2011https://doi.org/10.1089/cbr.2010.0885AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Something More than Estimating Renal Dosimetry." , 25(6), pp. 767–768FiguresReferencesRelatedDetailsCited byIndividualized Dosimetry of Kidney and Bone Marrow in Patients Undergoing 177 Lu-DOTA-Octreotate Treatment7 December 2012 | Journal of Nuclear Medicine, Vol. 54, No. 1Renal Dosimetry: Ready for BED? Response to the Italian Researchers Jeffry A. Siegel, Michael G. Stabin, and Robert M. Sharkey28 February 2011 | Cancer Biotherapy & Radiopharmaceuticals, Vol. 26, No. 1 Volume 25Issue 6Dec 2010 InformationCopyright 2010, Mary Ann Liebert, Inc.To cite this article:Lisa Bodei, Marta Cremonesi, and Giovanni Paganelli.Something More than Estimating Renal Dosimetry.Cancer Biotherapy and Radiopharmaceuticals.Dec 2010.767-768.http://doi.org/10.1089/cbr.2010.0885Published in Volume: 25 Issue 6: January 5, 2011PDF download