111In- and 90Y-DOTA-Lanreotide: Results and implications of the MAURITIUS trial

The high-level expression of somatostatin receptors (SSTR) on various tumor cells has provided the molecular basis for successful use of radiolabeled peptide analogues as tumor tracers in nuclear medicine. The vast majority of human tumors seem to overexpress one or the other of 5 distinct hSSTR subtype receptors. Whereas neuroendocrine tumors frequently overexpress human(h) SSTR2, intestinal adenocarcinomas frequently express hSSTR3 or hSSTR4, or both of these hSSTRs. In contrast to 111In-diethylenetriamine pentaacetic acid (DTPA)- DPhe 1-octreotide (OctreoScan ®; Mallinckrodt, Petten, NL), which binds to hSSTR2 and 5 with high affinity (K d 0.1–5 nmol/L), to hSSTR3 with moderate affinity (K d 10–100 nmol/L), and does not bind to hSSTR1 and hSSTR4, 111In/ 90Y-DOTA-lanreotide was found to bind to hSSTR2, 3, 4, and 5 with high affinity, and to hSSTR1 with lower affinity (K d 200 nmol/L). Based on its unique hSSTR binding profile, 111In-DOTA-lanreotide was suggested to be a potential radioligand for tumor diagnosis, and 90Y-DOTA-lanreotide suitable for receptor-mediated radionuclide therapy. When directly compared with 111In-DTPA- DPhe 1-octreotide and 111In-DOTA- DPhe 1-Tyr 3-octreotide, discrepancies in the scintigraphic imaging pattern are seen in about one third of tumor patients concerning both the tumor uptake as well as the detection of tumor lesions. On a molecular level, these discrepancies seem to be based on a higher high-affinity binding affinity of 111In-DOTA- DPhe 1-Tyr 3-octreotide for hSSTR2 (K d 0.1–1 nmol/L). Beneficial results of receptor-mediated experimental radionuclide therapy were first reported for high-dose treatment with 111In-DTPA- DPhe 1-octreotide, based on the emission of Auger electrons. Phase lla of the Multicenter Analysis of a Universal Receptor Imaging and Treatment Initiative, a European Study (MAURITIUS), shows in progressive cancer patients (therapy entry criteria) with a calculated tumor dose > 10 Gy/GBq 90Y-DOTA-lanreotide, the proof-of-principle for treating tumor patients with peptide receptor imaging agents. In the MAURITIUS study, cumulative treatment doses up to 232 mCi 90Y-DOTA-lanreotide were given as short-term intravenous infusion. Preliminary treatment results in 154 patients indicate stable tumor disease in 41% (63 of 154) of patients and regressive tumor disease in 14% (22 of 154) of tumor patients with different tumor entities expressing hSSTR. No severe acute or chronic hematologic toxicity, change in re