부산대학교 도서관

Purpose Improved therapies and imaging modalities are needed for the treatment of breast cancer brain metastases (BCBM). ANG1005 is a drug conjugate consisting of paclitaxel covalently linked to Angiopep-2, designed to cross the blood-brain barrier. We conducted a biomarker substudy to evaluate .sup.18F-FLT-PET for response assessment. Methods Ten patients with measurable BCBM received ANG1005 at a dose of 550 mg/m.sup.2 IV every 21 days. Before and after cycle 1, patients underwent PET imaging with .sup.18F-FLT, a thymidine analog, retention of which reflects cellular proliferation, for comparison with gadolinium-contrast magnetic resonance imaging (Gd-MRI) in brain metastases detection and response assessment. A 20 % change in uptake after one cycle of ANG1005 was deemed significant. Results Thirty-two target and twenty non-target metastatic brain lesions were analyzed. The median tumor reduction by MRI after cycle 1 was -17.5 % (n = 10 patients, lower, upper quartiles: -25.5, -4.8 %) in target lesion size compared with baseline. Fifteen of twenty-nine target lesions (52 %) and 12/20 nontarget lesions (60 %) showed a [greater than or equal to]20 % decrease post-therapy in FLT-PET SUV change (odds ratio 0.71, 95 % CI: 0.19, 2.61). The median percentage change in SUV.sub.max was -20.9 % (n = 29 lesions; lower, upper quartiles: -42.4, 2.0 %), and the median percentage change in SUV.sub.80 was also -20.9 % (n = 29; lower, upper quartiles: -49.0, 0.0 %). Two patients had confirmed partial responses by PET and MRI lasting 6 and 18 cycles, respectively. Seven patients had stable disease, receiving a median of six cycles. Conclusions ANG1005 warrants further study in BCBM. Results demonstrated a moderately strong association between MRI and .sup.18F-FLT-PET imaging.
Author(s): C. C. O'Sullivan[sup.1] [sup.2] , M. Lindenberg[sup.1] , C. Bryla[sup.1] , N. Patronas[sup.1] , C. J. Peer[sup.1] , L. Amiri-Kordestani[sup.1] , N. Davarpanah[sup.1] , E. M. Gonzalez[sup.1] , M. [...]