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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. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine whether there is evidence for hepatocellular radiation injury following treatment with 90Y-SMT487 (90Y-DOTA-tyr3-octreotide, OctreoTherTM) in patients with extensive liver metastases from neuroendocrine tumors. Patients reported in this study participated in a Phase II trial of efficacy and safety of 90Y-SMT487. The trial design called for three treatment cycles of 120 mCi each (4400 MBq) of 90Y-SMT487. 111In-pentetreotide SPECT images were used to determine the extent of liver metastases. Serum AST, ALT, and alkaline phosphatase levels were obtained at baseline and following each cycle of therapy. Least squares fit was applied to the serial liver enzyme measurements in patients with extensive liver metastases. Post-therapy liver enzyme measurements were also evaluated using WHO common toxicity criteria. Repeated-measures ANOVA and paired t-test were applied to the serial enzyme measures. There were 21 subjects. Fifteen of these had hepatic metastases with 12 demonstrating extensive (defined as 25% or more) liver involvement. In only 4 of these 15 did any of the three enzyme levels increase in WHO toxicity grade from baseline to final follow-up. We conclude that patients with diffuse SSTR positive hepatic metastases can be treated with a cumulative administered activity of 360 mCi 90Y-SMT487 with only a small chance of developing mild acute or subacute hepatic radiation injury. [ABSTRACT FROM AUTHOR]

AbstractThe purpose of this study was to evaluate the consistency of 3′-deoxy-3′[18F]fluorothymidine (FLT) standardized uptake values (SUVs) over the time course of imaging in head and neck cancer. Thirteen (13) subjects (all male; age: 56.9 ± 6.7 years) with squamous cell head and neck cancer, stage III/IV, were administered FLT and imaged dynamically for 1 hour over the tumor and then underwent whole-body (WB) imaging commencing at 74 ± 6 minutes. Imaging was repeated after 5 days of radiotherapy (10 Gy) and a single course of platinum-based chemotherapy. Volumes-of-interest (VOIs) were created on the last dynamic frame (SUV60). The pretherapy WB and midtherapy images were coregistered to the dynamic sequence and VOIs were applied. Mean and maximum SUVs (SUV60and SUVWB) and the change with treatment were evaluated. The correlations (Spearman's ρ) between SUV60and SUVWBfor all VOIs (pre- and midtherapy, n= 108 data pairs) were 0.98 for mean and 0.97 for maximum SUVs (p< 0.0001). Average absolute differences between SUV60and SUVWBwere 0.18 ± 0.15 and 0.29 ± 0.32 SUV units, respectively. Correlations (Spearman's ρ) between the change in SUV with therapy were 0.90 for mean and 0.89 for maximum SUV (p< 0.0001), with differences in the change values averaging 0.03 ± 0.36 and −0.17 ± 0.57 units, respectively. FLT SUVs are stable and comparable for images initiated between 55 and 100 minutes postinjection whether acquired pre- or midtherapy in head and neck cancer. [ABSTRACT FROM AUTHOR]