Dosimetric analyses of intra-arterial versus standard intravenous administration of lutetium-177-DOTA octreotate in patients with Neuroendocrine tumour liver dominant metastatic disease

Objectives: The aim of the present study was to perform image-based absorbed dose calculation and to determine whether hepatic intra-arterial (IA) injection of ¹⁷⁷Lu-DOTATATE Peptide Receptor Radionuclide Therapy (PRRT) would achieve higher intratumoral concentrations, thus leading to higher absorbed dose and higher efficacy than standard intravenous administration of ¹⁷⁷Lu-DOTATATE. Materials & Methods: Fifteen patients of GEP NETs with liver dominant metastatic disease treated with i.a 177Lu-DOTATATE after selective catheterization of the hepatic artery were enrolled into the study . 7.7 ± 1.1 GBq (range, 6.2-8.8 GBq, 170-240 mCi) of Lu-177 DOTATATE was administered as infusion into each patient over 5-10 mins along with positively charged amino acids for renal protection. For dosimetry, all patients underwent whole-body gamma scintigraphy (anterior and posterior planar acquisitions) and SPECT/CT of the abdomen at 2, 24 and 96 hours post 177Lu-DOTATATE administration. Dosimetric calculations were done using the HERMES software. Tumor to non-tumor (T/N) activity ratio was determined by volumes of interest (VOIs) drawn on 96 hrs post-treatment SPECT/CT on the tumour lesions and on the extra abdominal muscle for non-tumor uptake. Results: The tracer accumulation was clearly seen in the liver, spleen, kidneys, and in the tumor lesions in both the planar and SPECT/CT images. The mean dose per unit activity (D/A)was calculated as 0.17 ± 0.16 mGy/MBq in the liver, 0.55 ± 0.45 mGy/MBq for spleen, 0.35 ± 0.12 mGy/MBq for kidneys ,0.028 ± 0.01 mGy/MBq bone marrow and 4.18 ± 5.6 mGy/MBq for tumours. The D/A in the liver and tumor lesions differed significantly (p < 0.05) but differed insignificantly in spleen and kidneys (p>05) with the historical controls. The mean tumor/non-tumor concentration at 96 hrs was 76.83 ± 7.9 (range 10.2 - 251.3) whereas, it was 25.6 ± 5.9 (Range : 12 - 55) in the historical controls. This resulted in an average 3-fold increase in tumour concentration over the historical controls. The residence time of the activity was also significantly higher in liver and tumor lesions in patients treated with IA administration than with our historical controls.

Conclusions: Intra-arterial administration of 177Lu-DOTATATE seems to be a powerful tool over standard i.v administration for the improvement in clinical practice, by achieving higher concentration, retention and absorbed dose in tumors in patients of hepatic metastases of GEPNETs, although, the therapeutic efficacy of the IA infusion of PRRT cannot be commented post single administration. This needs to be further validated in larger number of patients treated with multiple cycles.