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The Quarterly Journal of Nuclear Medicine and Molecular Imaging 2012 December;56(6):551-8


lingua: Inglese

Super-selective hepatic arterial infusions as established technique (‘ARETAIEION’ Protocol) of [177Lu]DOTA-TATE in inoperable neuroendocrine liver metastases of gastro-entero-pancreatic (GEP) tumors

Limouris G. S. 1, Karfis I. 1, Chatzioannou A. 1, Paphiti M. I. 2, Lyra M. 1, Gennatas K. 1, Nikou G. 4, Voros D. 5, Pragulidis G. P. 5, Polydorou A. A. 5, Gouliamos A. 1

1 Nuclear Medicine Division, Radiology Department I, “Aretaieion” Hospital, Athens University Medical Faculty, Athens, Greece; 2 Nuclear Medicine Institute, UCLH, UK; 3 Department of Surgical Oncology, “Aretaieion” Hospital, Athens University Medical Faculty, Athens, Greece; 4 Section of Neuroendocrinology, Gastrointestinal Division, I Department of Propedeutic Internal Medicine, “Laikon” Hospital, Athens, Greece; 5 II Department of Surgery, “Aretaieion” Hospital, Athens University Medical Faculty, Athens, Greece


AIM: Aim of this study was to evaluate the effectiveness of non-carrier added (n. c. a.) [177Lu]DOTA-TATE in inoperable liver metastases, positive for sst2 receptor overexpression (verified by Octreoscan and confirmed by biopsy) due to neuroendocrine gastroenteropancreatic (GEP) tumors. [177Lu]DOTA-TATE has been infused after selective catheterization of the hepatic artery, minimising in parallel the toxicity of non-target tissues.
METHODS: The dose per session administered to each patient (12 cases in total) was 7400 MBq (200 mCi). Repetitions did not exceed 6-fold with treatment intervals of 5-8 weeks. Response assessment was classified according to the therapeutic benefit. Absorbed doses delivered to metastases, kidneys and red marrow were calculated according to OLINDA 1.1 program and the derived values were correlated to the Response Evaluating Criteria in Solid Tumors (RECIST). CT/MRI scans were performed as baseline before, during and after the end of treatment and monthly ultrasound images for follow-up estimation and measurements. Toxicity (World Health Organization criteria) was measured using blood and urine tests of renal, hepatic and bone marrow function.
RESULTS: None of the patients resulted complete response (0.0%); partial response was assessed in 8 (66.7%), disease stabilization in 3 (25%) and progressive disease in 1(8.3%). A 14-month median survival time was estimated for all patients, so far. Eight of 12 (66.7%) showed a mean target diameter shrinkage ranging from 33% to 45%. The organ average radiation dose estimation was found as follows: a) liver tumor 20.8 mGy/MBq; b) liver 0.14 mGy/MBq; c) kidneys 0.41 mGy/MBq; d) spleen 1.4 mGy/MBq; and f) bone marrow 0.022 mGy/MBq. The average absorbed dose per session to a tumor for a spherical mass of 20 g was estimated to be 20.8 mGy/MBq, depending on the histotype of the tumor. WHO toxicity grade 2 to 3 erythro-, leuko- and thrombo-cytopenia occurred in 9 (75%) cases observed about after the third session.
CONCLUSION: In unresectable metastatic liver lesions positive for somatostatin receptors repeated, trans-hepatic high doses of [177Lu]DOTA-TATE resulted in a more than promising therapeutic outcome with a partial response in 75% of the treated patients. Given the loco-regional modality character of the administration technique, no nephro-toxicity has been so far observed whereas a remarkable myelotoxicity was noticed.

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