Intratumoral conversion of 5-fluorocytosine to 5-fluorouracil by monoclonal antibody-cytosine deaminase conjugates: Noninvasive detection of prodrug activation by magnetic resonance spectroscopy and spectroscopic imaging

摘要: The monitoring of antibody-directed enzyme-prodrug therapies requires evaluation drug activation within the tissues interest. We have demonstrated feasibility noninvasive magnetic resonance spectroscopy and spectroscopic imaging (chemical shift imaging) to detect prodrug 5-fluorocytosine (5-FCyt) cytotoxic species 5-fluorouracil (5-FU) by monoclonal antibody-cytosine deaminase (CD) conjugates. In vitro , L6-CD but not 1F5-CD selectively metabolized 5-FCyt 5-FU on H2981 human lung adenocarcinoma cells because presence absence cell surface L6 CD20 antigens, respectively. After pretreatment tumor-bearing mice with L6-CD, in vivo metabolism tumors was detected 19F spectroscopy; chemical separation between resonances ∼1.2 ppm. levels were 50–100% 10–60 min after administration. Whole body (6 × 6 mm in-plane resolution) highest signal intensity tumor region. This study supports further development methods for preclinical clinical CD therapies.