Interpatient and intrapatient variability in organ absorbed doses during [177Lu]Lu-DOTATATE therapy for neuroendocrine tumors.
Abstract
Background
Peptide receptor radionuclide therapy (PRRT) with lutetium-177 labeled somatostatin analogues is an established treatment for patients with advanced neuroendocrine tumors (NETs). There is growing evidence of a dose-response relationship. Considering critical organ exposure, most patients are treated with fixed administered activities. Interpatient variability in absorbed dose per administered activity is observed, highlighting the need for treatment personalization. The objective was to evaluate interpatient variability in absorbed doses to critical organs during [¹⁷⁷Lu]Lu-DOTATATE therapy and intrapatient intercycle variability in absorbed doses to different organs across successive treatment cycles. MATERIAL AND
Methods
A dosimetric analysis was performed in ten patients with metastatic NETs undergoing PRRT with [¹⁷⁷Lu]Lu-DOTATATE. Each patient received four treatment cycles at approximately 8-week intervals. Quantitative single-photon emission computed tomography/computed tomography (SPECT/CT) imaging was acquired at 6, 24, 96 and 192 hours post-injection using a Siemens Symbia Intevo Bold system. Image reconstruction and dosimetric analysis were performed using Hermia and OLINDA/EXM 2.2. Organs were segmented on CT images and propagated to subsequent time points. Absorbed doses (Gy/GBq) were calculated for the kidneys, liver, spleen, and whole body.
Results
The sum of cycle-specific D/A₀ values after four treatment cycles ranged from 1.13 to 4.21 Gy/GBq for kidneys, 0.32 to 3.97 Gy/GBq for liver, 1.49 to 3.14 Gy/GBq for spleen and 0.07 to 0.22 Gy/GBq for total body. The greatest interpatient variability was observed in the liver. Intrapatient variability (CV) was highest for the liver (13.4 ± 6.5%), followed by the spleen (9.2 ± 3.6%) and kidneys (9.1 ± 4.4%), while whole-body variability remained minimal across treatment cycles.
Conclusions
Significant inter- and intrapatient variability in organ absorbed doses, particularly in the liver, supports the need for personalized dosimetry in [¹⁷⁷Lu]Lu-PRRT. These findings highlight the limitations of fixed-activity protocols and warrant further investigation of dose-toxicity relationships.