Method dependence, observer variability and kidney volumes in radiation dosimetry of 177Lu-DOTATATE therapy in patients with neuroendocrine tumours

Abstract

BackgroundRadionuclide therapy can be individualized by performing dosimetry. To determine absorbed organ doses in 177Lu-DOTATATE therapy, three methods based on activity concentrations are currently in use: the small volume of interest (sVOI) method, and two methods based on large VOIs either on anatomical CT (aVOI) or on thresholds on functional images (tVOI). The main aim of the present work was to validate the sVOI in comparison to the other two methods regarding agreement and time efficiency. Secondary aims were to investigate inter-observer variability for the sVOI and the change of functional organ volumes following therapy.MethodsThirty patients diagnosed with neuroendocrine tumours undergoing therapy with 177Lu-DOTATATE were included. Each patient underwent three SPECT/CT scans at 1, 4 and 7 days after the treatment. Three independent observers calculated absorbed doses to the right and left kidney and the spleen using sVOI and one observer used aVOI. For tVOI, the absorbed doses were calculated based on automatically drawn isocontours around the organs at different thresholds (42, 50, 60 and 70 %). The inter-observer difference between the calculated absorbed doses for sVOI was calculated, and the differences between the three methods were computed. Ratios of organ volumes acquired at days 1, 4 and 7 versus the volume at day 1 were calculated for the tVOI method.ResultsThe differences in results of the absorbed dose calculations using all the sVOI and tVOI were small (<5 %). Absorbed dose calculations using aVOI differed slightly more from these results but were still below 10 %. The differences between the three dose calculation methods varied between <5 and 10 %. The organ volumes derived from the tVOI were independent of time for the spleen while they decreased with time for the kidneys. The fastest analysis was performed with the sVOI method.ConclusionsAll three dose calculation methods rendered comparable results with small inter-observer differences for sVOI. Unlike the spleen, the functional volume of the kidneys decreased over time during therapy, which suggests that the absorbed dose calculation for the kidneys on activity concentrations should be performed for each time point. The sVOI is the preferred method for calculating absorbed doses in solid organs.

Kidney dosimetry during 177Lu-DOTATATE therapy in patients with neuroendocrine tumors: aspects on calculation and tolerance

“…When a maximum tolerated BED of 38 Gy to the kidney or an absorbed dose of 2 Gy to the bone marrow was applied, the kidney was the dose-limiting organ in 87%. The maximum number of 7.4 GBq therapy cycles per patient was five (2-14) based on the absorbed dose limits 23 Gy to kidneys and 2 Gy to bone marrow and eight (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) cycles when based on the 38 Gy BED limit to the kidneys and 2 Gy absorbed dose to the bone marrow (Figure 3). According to these results, by using these absorbed dose limits, about 2/3 of patients could receive more than the four cycles that has been considered a gold standard, while some patients (12%) would reach the dose limit after only 2-3 cycles.…”

“…The main aim of the Uppsala group, working on 177 Lu-DOTATATE PRRT dosimetry, has been dedicated to developing a clinically applicable and robust dosimetry protocol for solid organs based on 3-D imaging [19][20][21]. 177 Lu-DOTATATE PRRT dosimetry based on 2-D imaging suffers from problems when delineating healthy organ uptake due to overlaying uptake from tumors and physiological uptake in the bowel [8,27,28] and is instead best used to provide input data for cross-dose calculations.…”

“…In the SPECT images, small spherical volumes of interests (4 ml) were placed in both kidneys over the region of the highest activity as described previously [21]. This method (with PVE correction) has been shown to give an absorbed dose estimation that is close to a whole organ measurement [19] and it is much less time consuming to perform. Activity concentrations were determined for each time point and time-integrated activity concentration was calculated as the area under the curve of a single exponential fit (from injection start to infinity) to the time-activity concentration curve.…”

“…In a simulation study [18] it was stated that only a small percentage of the absorbed dose originated from the cross-dose from the surrounding organs and that the self-dose alone should therefore yield an accurate estimate of the absorbed dose. As previously reported [19][20][21], the self-dose can be calculated by multiplying the activity concentration for an organ/volume at the given time point by an almost size independent activity concentration dose factor.…”

A dosimetry procedure for organs-at-risk in 177Lu peptide receptor radionuclide therapy of patients with neuroendocrine tumours

“…In the present work, the mean activity concentration was sampled with multiple small VOIs in a healthy homogeneous part of each source volume on SPECT images. This method was proposed and supported by Sandström et al [35]. First, they showed that, compared to activity quantification on SPECT images, quantification based on planar images might artificially increase TIAC by 100% for the left kidney close to the spleen and by 50% for the right kidney close to the liver.…”