Dosimetric analysis of patients with gastro entero pancreatic neuroendocrine tumors (NETs) treated with PRCRT (peptide receptor chemo radionuclide therapy) using Lu-177 DOTATATE and capecitabine/temozolomide (CAP/TEM)

Abstract

Objective:: Two radiosensitizing chemotherapeutic drugs, capecitabine (CAP) and temozolomide (TEM), are administered concurrently to enhance the therapeutic efficacy of peptide receptor radionuclide therapy (PRRT). This study aims to assess the biodistribution and normal-organ and tumor radiation dosimetry for Lu-177 DOTATATE administered concurrently with CAP/TEM.

Methods:: 20 patients with non-resectable histologically confirmed gastroenteropancreatic neuroendocrine tumors with normal kidney function, a normal haematological profile and somatostatin receptor expression of the tumor lesions, as scintigraphically assessed by a Ga-68 DOTANOC scan, were included in two groups-case group (n = 10) and control group (n = 10). Patients included in case group were those who were advised concomitant CAPTEM therapy by the treating medical oncologist. Patients were administered CAP orally at a dose of 600mg m^-2 bovine serum albumin twice a day for 14 days starting 9 days prior to PRRT and oral TEM as a single dose at a dose of 75 mg m^-2 was given concurrently for the last 5 days commencing on the day of PRRT (days 9-14). In the control group, patients were treated with Lu-177 DOTATATE only. For PRRT, 6.4 GBq-7.6 GBq (173-207 mCi) of Lu-177 DOTATATE was administered as infusion into each patient over 10-15 min in a solution with positively charged amino acids for renal protection. Dosimetric calculations were done using the HERMES software.

Results:: Physiological uptake of Lu-177 DOTATATE was seen in all patients in liver, spleen kidneys, and bone marrow. Radiation absorbed doses (mean ± standard deviation) were obtained as 0.29 ± 0.12 mGy/MBq for kidneys, 0.30 ± 0.18 mGy/MBq for liver, 0.63 ± 0.37 mGy/MBq for spleen, 0.019 ± 0.001 mGy/MBq for bone marrow and 3.85 ± 1.74 mGy/MBq for tumours in the case group and they were 0.31± 0.26, 0.24 ± 0.14, 0.64 ± 0.42, 0.017 ± 0.016, 5.6 ± 11.27 mGy/MBq in kidneys, liver, spleen, bone marrow and neuroendocrine tumour, respectively, in the control group. Mann-Whitney U test between the variables of two groups showed an insignificant difference (p > 0.05).

Conclusions:: The authors demonstrated no significant difference between the tumor and organ doses with Lu-177 DOTATATE in the patients treated with and without concomitant chemotherapy.

Advances in knowledge:: To our knowledge, this is the first dedicated study exhibiting dosimetric analysis in patients undergoing PRRT in combination with chemotherapy.

Figure 1.

Whole-body anterior and posterior images after the therapeutic administration of Lu-177 DOTATATE at 2, 24 and 96 h with a standard marker of 1 mCi at the level of lateral malleolus.