177Lu‐[DOTA0,Tyr3] octreotate therapy in patients with disseminated neuroendocrine tumors: Analysis of dosimetry with impact on future therapeutic strategy

Department of Oncology, Lund University and Lund University Hospital, Lund, Sweden.
Cancer (Impact Factor: 4.89). 02/2010; 116(4 Suppl):1084-92. DOI: 10.1002/cncr.24796
Source: PubMed


(177)Lu-(DOTA0,Tyr3) octreotate is a new treatment modality for disseminated neuroendocrine tumors. According to a consensus protocol, the calculated maximally tolerated absorbed dose to the kidney should not exceed 27 Gy. In commonly used dosimetry methods, planar imaging is used for determination of the residence time, whereas the kidney mass is determined from a computed tomography (CT) scan.
Three different quantification methods were used to evaluate the absorbed dose to the kidneys. The first method involved common planar activity imaging, and the absorbed dose was calculated using the medical internal radiation dose (MIRD) formalism, using CT scan-based kidney masses. For this method, 2 region of interest locations for the background correction were investigated. The second method also included single-photon emission computed tomography (SPECT) data, which were used to scale the amplitude of the time-activity curve obtained from planar images. The absorbed dose was calculated as in the planar method. The third method used quantitative SPECT images converted to absorbed dose rate images, where the median absorbed dose rate in the kidneys was calculated in a volume of interest defined over the renal cortex.
For some patients, the results showed a large difference in calculated kidney-absorbed doses, depending on the dosimetry method. The 2 SPECT-based methods generally gave consistent values, although the calculations were based on different assumptions. Dosimetry using the baseline planar method gave higher absorbed doses in all patients. The values obtained from planar imaging with a background region of interest placed adjacent to the kidneys were more consistent with dosimetry also including SPECT. For the accumulated tumor absorbed dose, the first 2 of the 4 planned therapy cycles made the major contribution.
The results suggested that patients evaluated according to the conventional planar-based dosimetry method may have been undertreated compared with the other methods. Hematology and creatinine did not indicate any restriction for a more aggressive approach, which would be especially useful in patients with more aggressive tumors where there is not time for more protracted therapy.

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Available from: Sven-Erik Strand, Dec 30, 2014
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    • "Hepatobiliary elimination was included in the model, since intestinal activity is of concern in planarbased dosimetry as it overlaps with renal activity in the anterior-posterior (AP) direction (Garkavij et al., 2010). A compartment representing hepatocytic uptake and subsequent biliary excretion was therefore included in the model. "
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    ABSTRACT: Patient-specific image-based dosimetry is considered to be a useful tool to limit toxicity associated with peptide receptor radionuclide therapy (PRRT). To facilitate the establishment and reliability of absorbed-dose response relationships, it is essential to assess the accuracy of dosimetry in clinically realistic scenarios. To this end, we developed pharmacokinetic digital phantoms corresponding to patients treated with (177)Lu-DOTATATE. Three individual voxel phantoms from the XCAT population were generated and assigned a dynamic activity distribution based on a compartment model for (177)Lu-DOTATATE, designed specifically for this purpose. The compartment model was fitted to time-activity data from 10 patients, primarily acquired using quantitative scintillation camera imaging. S values for all phantom source-target combinations were calculated based on Monte-Carlo simulations. Combining the S values and time-activity curves, reference values of the absorbed dose to the phantom kidneys, liver, spleen, tumours and whole-body were calculated. The phantoms were used in a virtual dosimetry study, using Monte-Carlo simulated gamma-camera images and conventional methods for absorbed-dose calculations. The characteristics of the SPECT and WB planar images were found to well represent those of real patient images, capturing the difficulties present in image-based dosimetry. The phantoms are expected to be useful for further studies and optimisation of clinical dosimetry in (177)Lu PRRT.
    Physics in Medicine and Biology 08/2015; 60(15):6131-49. DOI:10.1088/0031-9155/60/15/6131 · 2.76 Impact Factor
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    • "When 90 Y is the radiopharmaceutical, either 111 In-or 86 Y-labeled peptides are used as a surrogate and 2 to 5 scans are collected up to 2-3 days p.i. [3]. These activity data are usually fitted by means of monoexponential functions [4] [5] [6], biexponential [3], or trapezoids [7]. The great value of dosimetry is an established tenet, nonetheless each experimental point requires time-consuming acquisitions. "
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    ABSTRACT: Kidney dosimetry in 177Lu and 90Y PRRT requires 3 to 6 whole-body/SPECT scans to extrapolate the peptide kinetics, and it is considered time and resource consuming. We investigated the most adequate timing for imaging and time-activity interpolating curve, as well as the performance of a simplified dosimetry, by means of just 1-2 scans. Finally the influence of risk factors and of the peptide (DOTATOC versus DOTATATE) is considered. 28 patients treated at first cycle with 177Lu DOTATATE and 30 with 177Lu DOTATOC underwent SPECT scans at 2 and 6 hours, 1, 2, and 3 days after the radiopharmaceutical injection. Dose was calculated with our simplified method, as well as the ones most used in the clinic, that is, trapezoids, monoexponential, and biexponential functions. The same was done skipping the 6 h and the 3 d points. We found that data should be collected until 100 h for 177Lu therapy and 70 h for 90Y therapy, otherwise the dose calculation is strongly influenced by the curve interpolating the data and should be carefully chosen. Risk factors (hypertension, diabetes) cause a rather statistically significant 20% increase in dose (t-test, P < 0.10), with DOTATATE affecting an increase of 25% compared to DOTATOC (t-test, P < 0.05).
    06/2013; 2013(1):935351. DOI:10.1155/2013/935351
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    • "When comparing the results from different studies, differences in kidney protection method, administered activity per treatment cycle, imaging technique, and methods for image analysis and dosimetry should be considered (Table 3). In one of the studies, different methods for imaging and dosimetric analysis were compared on the same patients, thus keeping the biological parameters constant: the lowest D/Aadministered was obtained using SPECT (0.81 to 0.90 Gy/GBq) compared to planar imaging and CV method (0.97 to 1.2 Gy/GBq) [20]. Similar results were obtained in another study despite the large uncertainty associated with the planar imaging-derived dose estimates in that study [19]. "
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    ABSTRACT: Background Lu-[DOTA0, Tyr3]-octreotate (177Lu-octreotate) is used to treat neuroendocrine tumors with high somatostatin-receptor expression. 177Lu-octreotate is mainly excreted via the kidneys, but to some extent, accumulates in the kidney cortex due to, e.g., tubular reabsorption. Renal toxicity is one of the main limiting factors in 177Lu-octreotate treatment. Further knowledge of the biodistribution and dosimetry of 177Lu-octreotate in individual patients is needed. The aim of this study was to estimate the absorbed dose to the kidneys and compare the results obtained with planar imaging and different dosimetric methods: (1) conjugate-view (CV) method using patient-specific kidney sizes, (2) PA method, based on posterior images only, (3) CV method with reduced number of time points (CVreduced data), and (4) CV method using standard kidney sizes (CVstandard size). Methods Totally, 33 patients each received 3.4 to 8.2 GBq of 177Lu-octreotate up to five times, with infusion of lysine and arginine to block the renal uptake. Whole-body planar gamma camera images were acquired on days 0, 1, 2, and 7. The 177Lu concentration in the kidneys was determined by the CV method, and the absorbed dose was estimated with patient-specific organ sizes. Comparison to the CV method was made using posterior images only, together with the influence of the number of time points and with standard organ sizes. Results Large interindividual variations were found in the time-activity curve pattern and in the absorbed dose to the kidneys using the CV method: 0.33 to 2.4 Gy/GBq (mean = 0.80 Gy/GBq, SD = 0.30). In the individual patient, the mean deviation of all subsequent kidney doses compared to that of the first administration was 1% (SD = 19%) and 5% (SD = 23%) for the right and left kidneys, respectively. Excluding data for day 7 resulted in large variations in the absorbed dose. Conclusion Large interindividual variations in kidney dose were found, demonstrating the need for patient-specific dosimetry and treatment planning.
    EJNMMI Research 09/2012; 2(1):49. DOI:10.1186/2191-219X-2-49
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