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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Acridines, Antineoplastic Agents, Area Under Curve, Fluorouracil, Humans, Neoplasms, Solubility.
user
Is early tumor drug pharmacokinetics influenced by tumor perfusion but not plasma drug exposure? Context: Pharmacokinetic parameters derived from plasma sampling are used as a surrogate of tumor pharmacokinetics. However, pharmacokinetics-modulating strategies do not always result in increased therapeutic efficacy. Nonsurrogacy of plasma kinetics may be due to tissue-specific factors such as tumor perfusion. To assess the impact of tumor perfusion and plasma drug exposure on tumor pharmacokinetics, positron emission tomography studies were done with oxygen-15 radiolabeled water in 12 patients, with 6 patients undergoing positron emission tomography studies with carbon-11 radiolabeled N-[2-(dimethylamino)ethyl]acridine-4-carboxamide and the other 6 with fluorine-18 radiolabeled 5-fluorouracil. We found that tumor blood flow (mL blood/mL tissue/minute) was significantly correlated to early tumor radiotracer uptake between 4 and 6 minutes [standard uptake value (SUV)4-6; rho = 0.79; P = 0.002], tumor radiotracer exposure over 10 minutes [area under the time-activity curve (AUC)0-10; predominantly parent drug; rho = 0.86; P < 0.001], and tumor radiotracer exposure over 60 minutes (AUC0-60; predominantly radiolabeled metabolites; rho = 0.80; P = 0.002). Similarly, fractional volume of distribution of radiolabeled water in tumor (Vd) was significantly correlated with SUV4-6 (rho = 0.80; P = 0.002), AUC0-10 (rho = 0.85; P < 0.001), and AUC0-60 (rho = 0.66; P = 0.02). In contrast, no correlation was observed between plasma drug or total radiotracer exposure over 60 minutes and tumor drug uptake or exposure. Tumor blood flow was significantly correlated to Vd (rho = 0.69; P = 0.014), underlying the interdependence of tumor perfusion and Vd.
assistant
Tumor perfusion is a key factor that influences tumor drug uptake/exposure. Tumor vasculature-targeting strategies may thus result in improved tumor drug exposure and therefore drug efficacy. Final Decision: yes