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Intra-arterial Radiopeptide Infusions with High Activity of 111In-Octreotide: From “Aretaieion Protocol” to the Temporal Intra-arterial Port Installation

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Liver Intra-arterial PRRT with 111In-Octreotide

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Abstract

Gastroenteropancreatic neuroendocrine tumors (NETs) are slow-growing malignancies, expressing somatostatin receptors on their cell membranes. These receptors can be targets for therapy with 111In-labeled somatostatin analogues. In 1996 Eric Krenning injected for the first time intravenously 111In-Octreotide (OctreoScan®, Mallinckrodt, Petten, the Netherlands) as a new treatment approach to confrontate particularly unresectable neuroendocrine tumors. In our Institution, we started treating this rare category of neoplasms exclusively injecting intra-arterially 111In-Octreotide, in high activities, focused our interest on liver metastases after catheterization of the hepatic artery (“Aretaieion Protocol”). The radiopeptide was infused in repeated doses ranging from 4.070 GBq (110 mCi) to 5.920 GBq (160 mCi) with a time interval between the sessions of 6–8 weeks. It was aimed to achieve a tumor-absorbed dose according to the dosimetry followed, over 70 Gy and tumoricidal results due to the effect of the Auger and Internal Conversion 111Indium’s Electron Emission. Follow-up at bi-monthly intervals was performed by means of ultrasonography (U/S) and every 6 months by contrast material-enhanced computed tomography (CT) and/or magnetic resonance imaging (MRI). This therapeutic procedure is described in detail in this chapter, based on the follow-up experience in more than 80 patients exceeding in total 800 intra-arterial catheterizations, in a time period of more than a decade. Advantages and limitations as a first-line treatment scheme for the management of this rare category of tumors are analyzed. In parallel with other authors tightly working in the field using 90Y- and/or 117Lu-labeled peptides, we predicted the dynamic of PRRT with 111In-Octreotide plus best supportive care (30 mg Octreotide LAR) as first-line therapy in progressive neuroendocrine tumors, 20 years before its final establishment as such in 2017, after Netter-1 study publication.

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Notes

  1. 1.

    Ki-67 is a nuclear antigen expressed in proliferating cells and is expressed during the GI, S, G2, and M phases of the cell cycle. Cells are then stained with a Ki-67 antibody, and the number of stained nuclei is then expressed as a percentage of total tumor cells. The name is derived from the city of origin (Kiel, Germany) and the “67” number of the original clone in the 96-well plate.

    The Mitotic Index, expressed as the number of cells per microscopic field is determined by counting the number of cells undergoing mitosis through a light microscope on hematoxylin and eosin (H and E) stained sections. Usually the number of mitotic figures is expressed as the total number in a defined number of high-power fields, i.e., 10 mitoses in 10 high power fields. Since the field of vision area can considerably vary between different microscopes, the exact area of the high-power fields should be defined in order to compare results from different studies.

  2. 2.

    Uptake on the OctreoScan was scored on planar images using a four-point scale; [grade 1: activity (uptake) equal to that in the normal liver, grade 2: activity (uptake) greater than that in the normal liver but less than that in the left kidney and spleen, grade 3: activity (uptake) equal to that in the left kidney, grade 4: activity (uptake) at least equal to the half of the sum of the activities in spleen and left kidney]. Purpose of this four-point scale is to assess candidacy for peptide receptor radionuclide therapy (PRRT), with a score mandatorily greater than 2, i.e., 3 and 4.

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  1. Nuclear Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Georgios S. Limouris

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    Georgios S. Limouris

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Limouris, G.S. (2021). Intra-arterial Radiopeptide Infusions with High Activity of 111In-Octreotide: From “Aretaieion Protocol” to the Temporal Intra-arterial Port Installation. In: Limouris, G.S. (eds) Liver Intra-arterial PRRT with 111In-Octreotide. Springer, Cham. https://doi.org/10.1007/978-3-030-70773-6_7

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