⁹⁰Y–DOTA–D‐Phe¹–Try³– octreotide in therapy of neuroendocrine malignancies

Abstract

Somatostatin receptors type 2 (sst(2)) are expressed in high concentration on numerous neudoendocrine tumors. The successful use of radiolabeled somatostatin analogs in imaging promoted further studies in utilizing them in radiopeptide therapy. The somatostatin analog [(90)Y-DOTA-D-Phe(1)-Try3]octreotide (DOTATOC) (DOTA: 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) possesses favorable characteristic for its therapeutic use; shows high affinity for sst(2), moderately high affinity for sst(5), and intermediate affinity for sst(3); high hydrophilicity; stable and facile labeling with (111) In and (90) Y. In this article we report our experience with (90)Y-DOTATOC in neuroendocrine tumors. Eighty-seven patients with neuroendocrine tumors were treated with a cumulated activity ranging from 7.4 to 20.2 GBq. Most patients responded with stabilization of disease (48%); however, objective responses were observed in 28% of patients (5% complete response). No major acute reactions were observed up to the activity of 5.55 GBq per cycle. The dose limiting was bone marrow toxicity and the maximal tolerated dose was defined as 5.18 GBq.

Zalecenia ogólne dotyczące postępowania w nowotworach neuroendokrynnych układu pokarmowego (rekomendowane przez Polską Sieć Guzów Neuroendokrynnych)

“…90 Y, or a combination of the two. Data from nonrandomised clinical studies indicates that a response to treatment (complete or partial remission) can be achieved in approximately 8-46% of patients, and the mean progression-free survival after the treatment is 25 to 36 months [133][134][135][136][137][138][139][140][141]. These studies apply mostly to patients with well-differentiated neoplasms (G1 and G2), and these recommendations are for this group of patients.…”

Long-Term Hematotoxicity After Peptide Receptor Radionuclide Therapy with 177Lu-Octreotate

“…Bone marrow suppression is regarded as one of the most serious side effects after PRRT (10)(11)(12)(13). Because of the lower energy and the shorter tissue penetration of the emitted b particles, treatment with 177 Lu-labeled peptides may result in a lower level of overall toxicity than PRRT with 90 Y-labeled peptides (14).…”

Pre-therapeutic dosimetry with radiolabelled somatostatin analogues in patients with advanced neuroendocrine tumours

“…It is known that the two peptides pentetreotide and DOTA-TOC have different affinity profiles on somatostatin receptors [1,2]. If pre-therapeutic dosimetry is demanded by an ethical committee or by authorities, we suggest the use of Y-DOTA-TOC base the dose on body surface area or use a kidney absorbed dose adapted scheme with dosimetric calculations during the first therapy cycle [3][4][5][6][7]. It is also known that the kidney volume plays a crucial role in the absorbed dose to the organ [8].…”