¹⁸FDG, [¹⁸F]FLT, [¹⁸F]FAZA, and¹¹C-Methionine Are Suitable Tracers for the Diagnosis andIn VivoFollow-Up of the Efficacy of Chemotherapy by miniPET in Both Multidrug Resistant and Sensitive Human Gynecologic Tumor Xenografts

Abstract

Expression of multidrug pumps including P-glycoprotein (MDR1, ABCB1) in the plasma membrane of tumor cells often results in decreased intracellular accumulation of anticancer drugs causing serious impediment to successful chemotherapy. It has been shown earlier that combined treatment with UIC2 anti-Pgp monoclonal antibody (mAb) and cyclosporine A (CSA) is an effective way of blocking Pgp function. In the present work we investigated the suitability of four PET tumor diagnostic radiotracers including 2-[18F]fluoro-2-deoxy-D-glucose (18FDG), 11C-methionine, 3′-deoxy-3′-[18F]fluorothymidine (18F-FLT), and [18F]fluoroazomycin-arabinofuranoside (18FAZA) for in vivo follow-up of the efficacy of chemotherapy in both Pgp positive (Pgp+) and negative (Pgp−) human tumor xenograft pairs raised in CB-17 SCID mice. Pgp+ and Pgp− A2780AD/A2780 human ovarian carcinoma and KB-V1/KB-3-1 human epidermoid adenocarcinoma tumor xenografts were used to study the effect of the treatment with an anticancer drug doxorubicin combined with UIC2 and CSA. The combined treatment resulted in a significant decrease of both the tumor size and the accumulation of the tumor diagnostic tracers in the Pgp+ tumors. Our results demonstrate that 18FDG, 18F-FLT, 18FAZA, and 11C-methionine are suitable PET tracers for the diagnosis and in vivo follow-up of the efficacy of tumor chemotherapy in both Pgp+ and Pgp− human tumor xenografts by miniPET.

K-Ras Activation Induces Differential Sensitivity to Sulfur Amino Acid Limitation and Deprivation and to Oxidative and Anti-Oxidative Stress in Mouse Fibroblasts

“…An exception is represented by melanoma cells, in which SLC6A15 is highly up-regulated. Therefore, the use of methionine uptake as a marker for proliferative activity in substitution of fluoro-deoxyglucose [ 85 , 86 ], or therapeutic use of dietary methionine restriction would benefit from knowledge of the expression of methionine transporters.…”

Assessment of Amino Acid/Drug Transporters for Renal Transport of [18F]Fluciclovine (anti-[18F]FACBC) in Vitro

“…Thus, [ 18 F]fluciclovine accumulation in the brain is likely restricted because of neutral amino acid efflux via AATs at the BBB. [ 11 C]Methionine, an amino acid PET tracer used in tumor detection, has some properties similar to those of [ 18 F]fluciclovine: (1) [ 11 C]methionine is transported via AATs [10]; (2) [ 11 C]methionine accumulates readily in the liver, moderately in the kidney, but accumulates little in the brain [29]; and (3) [ 11 C]methionine accumulation is not affected by P-gp expression [30]. Considering the similarity in the distribution mechanisms underlying [ 18 F]fluciclovine and [ 11 C]methionine, the present study suggests that, in contrast to that for most therapeutic drugs [31], AATs are the primary contributors to the hepatic, renal, and cerebral biodistribution of [ 18 F]fluciclovine.…”

Imaging of Preclinical Endometrial Cancer Models for Monitoring Tumor Progression and Response to Targeted Therapy

“…Although not yet tested clinically for EC, we have demonstrated the feasibility of FLT-PET to detect and monitor tumor growth in our EC mouse model [12]. For a number of different tumors including animal models of breast-and ovarian cancers, FLT-PET has been used to evaluate treatment response [54][55][56][57][58][59][60].…”

“…Several PET tracers for hypoxia have been developed and FMISO and 18 F-fluoroazomycin-arabinofuranoside (FAZA) represent two of the most common commercially available hypoxia tracers. Neither FAZA nor FMISO have been tested in preclinical or clinical EC, but both have shown promise for detection of hypoxic regions in cervical cancer [68,69] and in animal models of cervical and ovarian cancer [57,70,71].…”