Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease edition:7 location:Berlin, Germany date:11-12 March 2010
Introduction: Peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NETs) has emerged as a powerful palliative therapy. I.v. administration of radiolabeled (e.g. Yttrium-90) somatostatin analogues (SA) results in high-dose local irradiation of all tumor sites. The radiolabelled SA accumulates in the tumors through receptor-mediated internalization depending on the expression of somatostatin receptors and the pharmacokinetics of the radiolabelled SA. Aim(s): Antibody formation in patients treated with SA is extremely rare and has, until
now, only been described in four cases. Antibody formation
after PRRT with radiolabelled SA has never been documented.
We present a patient with an impressive change in biodistribution on 68Ga-DOTATOC PET/CT images performed after a first administration of 90Y-DOTATOC, most likely due to antibody formation against the SA. Materials and Methods: A 38-year-old female patient, diagnosed with a NET of the small intestine with lymph node and liver metastases and progressive under cold SA, was included in a 90Y-DOTATOC study protocol (four cycles of 1.85 GBq/m 2 90Y-DOTATOC). Pretherapeutic dosimetry with 111In-octreotide scintigraphy and baseline 68Ga-DOTATOC PET/CT showed no apparent abnormalities. Seven weeks after the first cycle, a 68Ga-DOTATOC PET/CT was performed to evaluate early treatment response. Results: Seven weeks after the first cycle, 68Ga-DOTATOC PET/CT showed a dramatic increase of the
blood pool activity and a decrease in activity in the liver metastases and in the spleen. A 68Ga-DOTATOC PET/CT, repeated within the same week and three months later, showed a similar biodistribution. SUVmax of the bloodpool, spleen, and largest liver metastasis changed from 43.97, 21.5 and 35.6 at baseline to 10.1, 7.55 and 8.49, respectively. A repeat dosimetry showed an increase in
the prospected red marrow dose after four cycles from 0.79 Gy at baseline to 2.01 Gy. The patient had no symptoms and all blood values were within normal limits. No further cycles of PRRT were administered based on these findings. Conclusion: We interpreted this drastic change in biodistribution as suggestive for antibody formation against the peptide, in concordance with findings
published after cold SA therapy. This altered biodistribution can cause significant changes in dosimetry in PRRT. In this case, the altered biodistribution resulted in a marked increase in red marrow dose. The potential effect of antibody formation against the peptide needs to be acknowledged by the PRRT community.