title: 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.
authors.affiliation: Iowa City Veterans Administration Hospital, Diagnostic Imaging and Radioisotope Therapy Service, Iowa City, IA 52240, USA. davie-bushnell@uiowa.edu
authors.forename: David
authors.initials: D
authors.lastname: Bushnell
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Menda
authors.forename: Thomas
authors.initials: T
authors.lastname: O'Dorisio
authors.forename: Mark
authors.initials: M
authors.lastname: Madsen
authors.forename: Sara
authors.initials: S
authors.lastname: Miller
authors.forename: Thomas
authors.initials: T
authors.lastname: Carlisle
authors.forename: Shayne
authors.initials: S
authors.lastname: Squires
authors.forename: Daniel
authors.initials: D
authors.lastname: Kahn
authors.forename: Wayne
authors.initials: W
authors.lastname: Walkner
authors.forename: Mary
authors.initials: M
authors.lastname: Connolly
authors.forename: Sue
authors.initials: S
authors.lastname: O'Dorisio
authors.forename: Mark
authors.initials: M
authors.lastname: Karwal
authors.forename: James
authors.initials: J
authors.lastname: Ponto
authors.forename: Hakim
authors.initials: H
authors.lastname: Bouterfa
mesh_terms: D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000008:administration & dosage* / Q000494:pharmacology*; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology; D002276:Carcinoid Tumor / Q000378:metabolism / Q000532:radiotherapy; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000532:radiotherapy; D008239:Lysine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008579:Meningioma / Q000378:metabolism / Q000532:radiotherapy; D008875:Middle Aged; D015282:Octreotide / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000532:radiotherapy; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D015021:Yttrium Radioisotopes / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000596:Amino Acids; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; D001120:Arginine; D008239:Lysine; D015282:Octreotide; C106246:Edotreotide