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• W2266585575 abstract "PURPOSE: To evaluate tumor, normal tissue, and plasma pharmacokinetics of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA). The study aimed to determine the pharmacokinetics of carbon-11–labeled DACA ([ 11 C]DACA) and evaluate the effect of pharmacologic doses of DACA on radiotracer kinetics. PATIENTS AND METHODS: [ 11 C]DACA (at 1/1,000 phase I starting dose) was administered to 24 patients with advanced cancer (pre–phase I) or during a phase I trial of DACA in five patients. Positron emission tomography (PET) was performed to assess pharmacokinetics and tumor blood flow. Plasma samples were analyzed for metabolite profile of [ 11 C]DACA. RESULTS: There was rapid systemic clearance of [ 11 C]DACA over 60 minutes (1.57 and 1.46 L·min -1 ·m -2 in pre–phase I and phase I studies, respectively) with the production of several radiolabeled plasma metabolites. Tumor, brain, myocardium, vertebra, spleen, liver, lung, and kidneys showed appreciable uptake of 11 C radioactivity. The area under the time-versus-radioactivity curves (AUC) showed the highest variability in tumors. Of interest to potential toxicity, maximum radiotracer concentrations (Cmax) in brain and vertebra were low (0.67 and 0.54 m 2 ·mL -1 , respectively) compared with other tissues. A moderate but significant correlation was observed for tumor blood flow with AUC (r = 0.76; P = .02) and standardized uptake value (SUV) at 55 minutes (r = 0.79; P = .01). A decrease in myocardial AUC ( P = .03) and splenic and myocardial SUV ( P = .01 and .004, respectively) was seen in phase I studies. Significantly higher AUC, SUV, and Cmax were observed in tumors in phase I studies. CONCLUSION: The distribution of [ 11 C]DACA and its radiolabeled metabolites was observed in a variety of tumors and normal tissues. In the presence of unlabeled DACA, pharmacokinetics were altered in myocardium, spleen, and tumors. These data have implications for predicting activity and toxicity of DACA and support the use of PET early in drug development." @default.
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• W2266585575 date "2001-03-01" @default.
• W2266585575 modified "2023-10-13" @default.
• W2266585575 title "Pharmacokinetic Evaluation of N-[2-(Dimethylamino)Ethyl]Acridine-4-Carboxamide in Patients by Positron Emission Tomography" @default.
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• W2266585575 doi "https://doi.org/10.1200/jco.2001.19.5.1421" @default.
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