Dosimetry after peptide receptor radionuclide therapy: impact of reduced number of post-treatment studies on absorbed dose calculation and on patient management

Abstract

Background: After each cycle of [¹⁷⁷Lu]-DOTA-TATE peptide receptor radionuclide therapy (PRRT) dosimetry is performed to enable precise calculation of the radiation-absorbed dose to tumors and normal organs. Absorbed doses are routinely calculated from three quantitative single-photon emission computed tomography (SPECT) studies corrected by computed tomography (CT) acquired at t₁ = 24 h, t₂ = 96 h, and t₃ = 168 h after the first cycle of treatment. After following cycles, a single SPECT/CT study is performed. The aim of the present study is to assess the feasibility of a "two time point" quantitative SPECT/CT protocol after the first PRRT cycle and its impact on patient management. Quantitative SPECT/CT data of 25 consecutive patients with metastatic neuroendocrine tumors after PRRT were retrospectively analyzed. Radiation-absorbed doses calculated using the standard protocol with three SPECT/CT studies acquired at (t₁, t₂, t₃) were compared to those obtained from three different "two time point" protocols with SPECT/CT studies performed at (t₁, t₂), (t₁, t₃), or (t₂, t₃).

Results: The best agreement for the cumulative doses absorbed by the kidneys, bone marrow, liver, spleen, and tumors with the conventional protocol was obtained with the (t₁, t₃) protocol with mean relative differences of - 1.0% ± 2.4%, 0.4% ± 3.1%, - 0.9% ± 4.0%, - 0.8% ± 1.1%, and - 0.5% ± 2.0%, respectively, and correlation coefficients of r = 0.99 for all. In all patients, there was no difference in the management decision of whether or not to stop PRRT because of unsafe absorbed dose to risk organs using either the standard protocol or the (t₁, t₃) protocol.

Conclusion: These preliminary results demonstrate that dosimetry calculations using two quantitative SPECT/CT studies acquired at 24 and 168 h after the first PRRT cycle are feasible and are in good agreement with the standard imaging protocol with no change in patient management decisions, while enabling improved patient comfort and reduced scanner and staff time.

Keywords: Dosimetry; Peptide receptor radionuclide therapy (PRRT); SPECT/CT; [177Lu]-DOTA-TATE.

Fig. 1

Chart of patient inclusion. n_p represents the number of patients included in the study and n_trt is the corresponding total number of therapy cycles

Fig. 2

Expected dose after the last PRRT calculated from the previous ones (1 to 3) using the standard “3 time-points” protocol (black stars) or the different “2 time-points’ protocols (triangles). Each vertical line represents a patient and the dashed region the unsafe dose region and interruption of the treatment (patients # 1, 8, 9, 13, and 25 following the standard protocol)

Fig. 3

Management of the 25 patients included in the study based on the kidney cumulative dose “predicted” after one, two, or three post-treatment scan(s) (PTS) and calculated either by using the standard protocol or by using the (t₁, t₃) or (t₂, t₃) “2 time-points” protocols with a safety threshold fixed at a 25 Gy and b 30 Gy. Each color bar represents different protocol. Horizontal lines delimit the different managements of the patient (4 CYCLES: the patient can receive 4 cycles of treatment safely, 1 PTS only; 4 CYCLE—2 PTS: the patient can receive 4 cycles of treatment safely, 2 PTS only; CONSIDER A fourth CYCLE—3 PTS: consider to administer a fourth cycle of treatment based on the probability to exceed the safety threshold after 4 cycles; 3 CYCLES—2 PTS: the patient can receive only 3 cycles of treatment safely, 2 PTS only; CONSIDER A third CYCLE—2 PTS: consider to administer at maximum a third cycle of treatment based on the probability to exceed the safety threshold after 3 cycles; STOP TREATMENT—1 cycle: stop treatment after a single cycle of treatment)

Fig. 4

Bland and Altman plots showing differences in the kidney-absorbed dose a after the first PRRT cycle and b after completion of the treatment, computed using the standard protocol and the “2 time-points” (i) (t₁, t₂), (ii) (t₁, t₃), or (iii) (t₂, t₃) protocols, with 95% limits of agreement (mean ± 1.96 SD)

Fig. 5

Bland and Altman plots showing differences in the dose absorbed by tumors a after the first PRRT cycle and b after completion of the treatment, computed using the standard protocol and the “2 time-points” (i) (t₁, t₂), (ii) (t₁, t₃), or (iii) (t₂, t₃) protocols, with 95% limits of agreement (mean ± 1.96 SD). For clarity reason, an outlier cumulative tumor-absorbed dose point calculated with the (t₁, t₂) protocol is not shown at (x, y) = (81 Gy, − 113%).