Lu-177-[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
    • "An alternative to tomographic imaging is to use planar gamma-camera imaging, for which uncertainties in activity quantification have also been analysed (Norrgren et al 2003). However, for renal dosimetry in 177 Lu-PRRT, planar-based quantification suffers from problems caused by activity in the intestines being superpositioned on the kidneys in the images (Garkavij et al 2010). Internal dosimetry can be considered a multi-step process with an uncertainty associated with each step (Stabin 2008). "
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    ABSTRACT: A computer model of a patient-specific clinical (177)Lu-DOTATATE therapy dosimetry system is constructed and used for investigating the variability of renal absorbed dose and biologically effective dose (BED) estimates. As patient models, three anthropomorphic computer phantoms coupled to a pharmacokinetic model of (177)Lu-DOTATATE are used. Aspects included in the dosimetry-process model are the gamma-camera calibration via measurement of the system sensitivity, selection of imaging time points, generation of mass-density maps from CT, SPECT imaging, volume-of-interest delineation, calculation of absorbed-dose rate via a combination of local energy deposition for electrons and Monte Carlo simulations of photons, curve fitting and integration to absorbed dose and BED. By introducing variabilities in these steps the combined uncertainty in the output quantity is determined. The importance of different sources of uncertainty is assessed by observing the decrease in standard deviation when removing a particular source. The obtained absorbed dose and BED standard deviations are approximately 6% and slightly higher if considering the root mean square error. The most important sources of variability are the compensation for partial volume effects via a recovery coefficient and the gamma-camera calibration via the system sensitivity.
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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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    • "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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