Radiation exposure of the spleen during 177Lu-DOTATATE treatment and its correlation with haematological toxicity and spleen volume

Abstract

BackgroundSomatostatin analogue-based radionuclide therapy with 177Lu-DOTATATE is an important treatment option for patients with advanced neuroendocrine tumours overexpressing somatostatin receptors. In addition to the kidneys, the bone marrow is a major dose-limiting organ. The correlation between developed haematological toxicity and absorbed dose to the bone marrow is poor, which indicates that other factors affect haematological response. The spleen has an important role in the haematopoetic system, including being a reservoir for blood cells. It is also the organ that receives the highest mean absorbed dose during 177Lu-DOTATATE treatment. The aim of this study was to analyse mean absorbed dose to the spleen and its correlation with haematological toxicity, and to explore changes in splenic volume.The study included 41 patients treated with 7.2 GBq (3.5–8.3 GBq) of 177Lu-DOTATATE on two to five occasions. Following each fraction, planar whole-body scans were acquired at 2, 24, 48, and 168 h, and a SPECT/CT at 24 h post-injection. Mean absorbed spleen dose was calculated utilising planar images for time-activity data and SPECT to adjust activity amounts. Splenic volume information was collected from diagnostic CT scans at baseline and follow-up.ResultsMedian and total absorbed spleen doses were estimated to 4.5 and 15 Gy, respectively. Total absorbed spleen dose correlated with decrease in Hb (p = 0.02), but not WBC (p = 0.31) or PLT (p = 0.65) counts. For patients without bone metastases, mean absorbed spleen dose correlated with decrease in PLT (p = 0.04) but not Hb (p = 0.16) or WBC (p = 0.42) counts. The spleen volume was reduced to 75 % (p < 0.001) of original values (200 vs. 260 ml) at a mean follow-up of 36 months.ConclusionsHaematological toxicity according to Hb counts was moderately but significantly correlated with total absorbed spleen dose. This supports the possibility that radiation exposure of the spleen affects overall haematological response during 177Lu-DOTATATE treatment.

Significance of splenic uptake on somatostatin receptor imaging studies

“…Hematological toxicity according to hemoglobin counts was moderately but significantly correlated with total absorbed spleen dose which supported the possibility that radiation exposure of the spleen affects overall hematological response during Lu-177 DOTATATE treatment [33]. On the other hand, a previous study has reported that hematological toxicity after peptide receptor radionuclide therapy is not related to the radiation dose to the spleen [34].…”

Comparison of commercial dosimetric software platforms in patients treated with 177Lu‐DOTATATE for peptide receptor radionuclide therapy

“…Several articles already reported on patient dosimetry of 177 Lu-DOTATATE. 1,5,8,11,[63][64][65][66][67][69][70][71][72] Our objective was to assess the performance of existing commercial solutions for dosimetry purposes, which is why we selected a reduced number of clinical cases and organs, and did not considered tumors or image-based bone marrow dosimetry.…”

Imaging DNA Damage Repair In Vivo After 177Lu-DOTATATE Therapy

“…9). Given the very low uptake of 177 Lu in the mouse spleen (0.43±0.23%ID/g at 72 h), radiation exposure seems an unlikely source in mouse, although in humans the spleen receives a non-negligible dose following 177 Lu-DOTATATE (4.5-15 Gy over 2-5 cycles) (27). Notably, in our experimental setup, we observed no differences in the uptake of 111 Inanti-γH2AX-TAT in the kidneys of the mice, the tissue that is exposed most to 177 Lu radiation dose, second only to the tumor.…”