Receptor-mediated radiotherapy with 90Y-DOTA-DPhe1-Tyr3-octreotide: The experience of the european institute of oncology group1

https://doi.org/10.1053/snuc.2002.31563Get rights and content

High concentrations of subtype 2 somatostatin tumor receptors (sst2) are expressed in numerous tumors, enabling primary and metastatic masses to be localized by scintigraphy after injecting 111In-labeled somatostatin analogue octreotide. In addition to neuroendocrine tumors, somatostatin receptors have been identified on cancers of the central nervous system, breast, lung, and lymphatic tissue, and the use of radionuclide-labeled somatostatin analogues appeared promising for therapy as well as for diagnosis of such malignancies. The somatostatin analogue [DOTA-DPhe1-Tyr3] octreotide (DOTATOC) possesses favorable characteristics for its potential therapeutic use in that it shows high affinity for sst2, moderately high affinity for sst5, and intermediate affinity for sst3, high hydrophilicity, stable and facile labeling with 111In and 90Y. We began to investigate the potential therapeutic applications of 90Y DOTATOC in 1997 by performing a thorough dosimetric study in 18 patients who were administered 11In DOTATOC to estimate the absorbed doses during 90Y-DOTATOC therapy. Then, we moved on and treated an overall number of 256 patients, mostly recruited in 2 distinct protocols with and without the administration of kidney protecting agents, with 90Y DOTATOC. No major acute reactions were observed up to the activity of 5.55 GBq per cycle. The MTD per cycle was defined as 5.18 GBq. Objective therapeutic responses were documented in more than 20% of patients in terms of partial and complete responses. The present article reports in detalis our clinical experience (still ongoing) and outcomes with the use of 90Y DOTATOC.

References (29)

  • HeppelerA et al.

    Receptor targeting for tumor localisation and therapy with radiopeptides

    Curr Med Chem

    (2000)
  • MoiMK et al.

    The peptide way to macrocyclic bifunctional chelating agents: Synthesis of 2-(p-nitroben-zyl)-1,4,7,10-tetraazacyclododecane-N,N′,N′',N′''-tetra-acetic acid and study of its Yttrium(III) complex

    J Am Chem Soc

    (1988)
  • DeshpandeSV et al.

    Yttrium-90-labeled monoclonal antibody for therapy: Labeling by a new macrocyclic bifunctional chelating agent

    J Nucl Med

    (1990)
  • HeppelerA et al.

    Radiometal-labelled macrocyclic chelator-derivatised somatostatin analogue with superb tumour-targeting properties and potential for receptor-mediated internal radiotherapy

    Chem Eur J

    (1999)
  • Cited by (125)

    • Advances in Peptide Receptor Radionuclide Therapy

      2016, Seminars in Nuclear Medicine
    View all citing articles on Scopus
    1

    Supported by grants of the Italian association for Cancer Research (AIRC) and Consiglio Nazionale delle Ricerche (CNR-MIUR) PS Oncologia.

    View full text