Effects of Intravenous Amino Acid Administration with Y-90 DOTA-Phe1-Tyr3-Octreotide (SMT487[OctreoTher™]) Treatment

Abstract

Y-90-DOTA-Phe1-Tyr3-Octreotide (90Y-SMT 487, OctreoTher) has shown potential for effectively treating patients with neuroendocrine tumors. The dose-limiting organ for this agent is the kidney. The purpose of this work is to assess the effectiveness of a commercially available amino acid solution on reducing renal uptake of 90Y-SMT 487 and determine the safety profile of this solution. Subjects with In-111 pentetreotide positive tumors and normal creatinine levels were treated with 3 cycles of 90Y-SMT 487, 120 mCi/cycle, at 6-9 week intervals. During each treatment two liters of an amino acid solution containing arginine and lysine (Aminosyn II 7%, Abbott Laboratories, Abbott Park, IL) were infused IV over 4 hours. Adverse events were recorded. To assess the effect of Aminosyn II on renal uptake of 90Y-SMT 487, a subgroup of subjects underwent bremsstrahlung imaging 24 hours following infusion. Kidney to liver (K/L) count density ratios were generated from the baseline In-111 pentetreotide images (performed without amino acid infusion) and the 90Y bremsstrahlung images. Follow-up creatinine levels were obtained. Thirty-seven subjects received a total of 89 90Y-SMT 487 treatments. The number of amino-acid infusions associated with one or more episodes of emesis was 53 (62%). During 13 (15%) of these infusions, the Aminosyn II rate had to be reduced because of severe nausea and vomiting. Symptomatic flushing occurred during 16 (18%) of the infusions. One subject experienced a near syncopal event shortly after completing the infusion. Creatinine levels remained normal in 34 of 36 subjects during a mean follow-up period of 9.8 months. Fourteen subjects underwent bremsstrahlung imaging following infusion of 90Y-SMT 487. Kidney uptake appeared to decrease with administration of the amino acid solution in 13 of 14 subjects. For the 28 individual kidneys, the mean percent decrease in the Kidney/Liver uptake ratio with the amino acid solution was found to be 32%. We conclude that 2 L of Aminosyn II 7% infused over 4 hours appears to notably reduce renal uptake of 90Y-SMT 487. Aminosyn is generally well tolerated, particularly at lower infusion rates with occasional moderate to severe nausea and vomiting at higher rates.

Safety and Efficacy of Radionuclide Therapy with High-Activity In-111 Pentetreotide in Patients with Progressive Neuroendocrine Tumors

“…Our findings are consistent with other published clinical trials of 111 In-pentetreotide therapy, which also demonstrated disease stabilization or partial disease regressions with cumulative activity up to 500 mCi. 9,[12][13][14]18,19 These studies have also reported decreases in hormone levels ranging from 0%-40% of patients and improvement in clinical symptoms in up to 60% of patients. Our study reported significantly higher hormonal and clinical responses of 77% and 83% of patients, respectively, which may be due to the higher cumulative activity used.…”

ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms: Peptide Receptor Radionuclide Therapy with Radiolabelled Somatostatin Analogues

“…However, the most commonly used regimen is that developed by the Erasmus Medical Center, which recommends 25 g lysine and 25 g arginine in 1 L saline infused over 4 h, starting 30 min before the administration of the radiopharmaceutical. Alternatively, other commercially available amino acid solutions can be used [73]. The infusion of amino acids can be associated with hyperkalaemia so it may be prudent to correct high potassium levels prior to treatment or to enhance potassium excretion from the kidneys in patients with levels in the upper end of the normal range by use of a loop diuretic during amino acid infusion [74].…”

Detecting Tumor Metastases

“…Radiolabeled octreotides such as [ 123 I]Tyr3-octreotide (Krenning et al, 1989), [ 111 In]DTPA-D-Phe-octretide (Bakker et al, 1991), and [ 94m Tc]Tyr3-octreotate (Rogers et al, 2005) have been tested for nuclear imaging probes targeting SSTr2. Y-90 DOTA-Phe1-Tyr3-octreotide has been used to treat neuroendocrine tumors (Bushnell et al, 2004). NIS can also be used as a theranostic gene by using [ 99m Tc]pertechnetate and [ 124 I]NaI as SPECT and PET tracer, respectively (Chung, 2002), and [ 131 I]NaI (Dadachova & Carrasco, 2004) or [188Re] (Kang et al, 2004) for therapeutic radionuclides.…”