Accuracy of kidney dosimetry performed using simplified time activity curve modelling methods: a ¹⁷⁷Lu-DOTATATE patient study

Abstract

177Lu-DOTATATE therapy has been shown to produce encouraging results in treatment of neuroendocrine tumours (NETs). Unfortunately, since dosimetry for radionuclide therapy is considered to be challenging, typically similar amount of radiopharmaceutical is administered to every patient. There is growing evidence that the efficacy of this therapy can be significantly improved by employing personalized protocols, based on the organ-at-risk dosimetry. The aim of this study is to propose a practical and accurate dosimetry protocol based on the simplified acquisition schedules. Data from fifty-three therapy cycles in thirty-nine NET patients were analyzed. Three SPECT/CT scans, acquired at 4 h (D0), 23 h (D1) and 70 h (D3) after injection, were performed. The kidney volume was determined using CT and the activity was determined from quantitative SPECT using an iterative thresholding method. For each dataset, four methods were used to model the time-activity-curves (TAC): M1—two trapezoid segments (0 to D0 and D0 to D1), followed by monoexponential fit to D1 + D3 data; M2—monoexponential fit to D0 + D1 + D3 data; M3 and M4—monoexponential fit to D0 + D3 and D1 + D3 data, respectively. Additionally, kidney doses obtained from single time point method using a monoexponential curve with the population mean effective half-life, normalized to activities at D0 or D1 or D3 points, were calculated. The accuracy of simplified dosimetry methods was assessed as the percentage difference relative to doses calculated from M1. The major contribution to the absorbed dose estimate comes from the area under the late time portion of the TAC (D1 to infinity). Therefore, information from the late scan (D3) is crucial for the determination of kidney absorbed doses. Single time point method using monoexponential TAC, with the population mean effective half-life normalized to the late data point (48–72 h for kidneys) produces <10% deviation in the absorbed dose estimation, thus is recommended for clinical use.

Feasibility of single-time-point dosimetry for radiopharmaceutical therapies

“…Combining the results of kidneys, bone marrow and tumors for 177 Lu-DOTATATE, SPECT scanning at 72 h p.i. should be considered as optimal, while early time points, such as 48 h p.i., would be better for 177 Lu-PSMA therapies, in agreement with findings from studies published by Wei et al and Jackson et al (6,7). Equally accurate results could be achieved when using Method 1 and Method 2 when the suggested scan time are employed.…”

“…To address this challenge, with the aim of enabling routine dosimetry in the clinic, a number of simplified approaches have been proposed. One approach is to perform dosimetry estimation using only a single SPECT scan (single-time-point (STP) dosimetry) (3)(4)(5)(6)(7); in particular, see the recent discussion by Hänscheid and Lassmann (8).…”

“…Inspired by these works, we recently investigated accuracy of STP dosimetry for kidneys using different scan time points (4h, 24h and 72h post activity injection): data from 53 177 Lu-DOTATATE neuroendocrine tumors in radioligand therapy of 39 patients were used (6). The impact of the deviation of the particular patient's from on the accuracy of kidney doses was estimated.…”

Personalized radiation dosimetry for PRRT—how many scans are really required?

“…Others have addressed issues of reducing the number of post-treatment scans, even suggesting methods based on a single scan [7][8][9][10][11], but so far, the dependence on time points used for the suggested methods for dosimetry based on fewer scans has mostly been widely tested only for kidney dosimetry and not generally validated for normal organs and tumors. Furthermore, validation was not always performed with late time points (1 week) included in the reference method, as recommended by MIRD [12] to avoid substantial extrapolations in the calculation of absorbed dose.…”

A Novel Time–Activity Information-Sharing Approach Using Nonlinear Mixed Models for Patient-Specific Dosimetry with Reduced Imaging Time Points: Application in SPECT/CT After 177Lu-DOTATATE

“…Exponential functions are customarily used to fit the measured time-activity data, and two or three sampling points per exponential term and measurement period up to three to five times the effective half-life are recommended (3). A number of recent studies have considered simplified personalized renal dosimetry in PRRT (4)(5)(6)(7)(8)(9)(10)(11)(12) and Lu177-PSMA therapy (13,14). In particular, methods for approximating the PRRT TIA using a single activity measurement, introduced for Lu-177 DOTATATE by Hanscheid et al (4) and for Y-90 DOTATOC by Madsen et al (5), have gained popularity.…”