sup.68Ga-TRAP

• Published in: PloS one Vol. 11; no. 12; p. e0168248
• Main Authors: Kazmierczak, Philipp M, Todica, Andrei, Gildehaus, Franz-Josef, Hirner-Eppeneder, Heidrun, Brendel, Matthias, Eschbach, Ralf S, Hellmann, Magdalena, Nikolaou, Konstantin, Reiser, Maximilian F, Wester, Hans-Jürgen, Kropf, Saskia, Rominger, Axel, Cyran, Clemens C
• Format: Journal Article
• Language: English
• Published: Public Library of Science 19.12.2016
• Subjects: Breast cancer; Care and treatment; Development and progression; Gene expression; Genetic aspects; Health aspects; Integrins; Radioactive tracers
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0168248

To investigate .sup.68 Ga-TRAP-(RGD).sub.3 hybrid imaging for the in vivo monitoring of [alpha].sub.v ß.sub.3 -integrin expression as biomarker of anti-angiogenic therapy effects in experimental breast cancer. Human breast cancer (MDA-MB-231) xenografts were implanted orthotopically into the mammary fat pads of n = 25 SCID mice. Transmission/emission scans (53 min to 90 min after i.v. injection of 20 MBq .sup.68 Ga-TRAP-(RGD).sub.3) were performed on a dedicated small animal PET before (day 0, baseline) and after (day 7, follow-up) a 1-week therapy with the VEGF antibody bevacizumab or placebo (imaging cohort n = 13; therapy n = 7, control n = 6). The target-to-background ratio (TBR, VOImax.sub.tumor /VOImean.sub.muscle) served as semiquantitative measure of tumor radiotracer uptake. Unenhanced CT data sets were subsequently acquired for anatomic coregistration and morphology-based tumor response assessments (CT volumetry). The imaging results were validated by multiparametric ex vivo immunohistochemistry ([alpha].sub.v ß.sub.3 -integrin, microvascular density-CD31, proliferation-Ki-67, apoptosis-TUNEL) conducted in a dedicated immunohistochemistry cohort (n = 12). .sup.68 Ga-TRAP-(RGD).sub.3 binding was significantly reduced under VEGF inhibition and decreased in all bevacizumab-treated animals ([DELTA]TBR.sub.follow-up/baseline : therapy -1.07±0.83, control +0.32±1.01, p = 0.022). No intergroup difference in tumor volume development between day 0 and day 7 was observed ([DELTA]volume.sub.therapy 134±77 [mu]L, [DELTA]volume.sub.control 132±56 [mu]L, p = 1.000). Immunohistochemistry revealed a significant reduction of [alpha].sub.v ß.sub.3 -integrin expression (308±135 vs. 635±325, p = 0.03), microvascular density (CD31, 168±108 vs. 432±70, p = 0.002), proliferation (Ki-67, 5,195±1,002 vs. 7,574±418, p = 0.004) and significantly higher apoptosis (TUNEL, 14,432±1,974 vs. 3,776±1,378, p = 0.002) in the therapy compared to the control group. .sup.68 Ga-TRAP-(RGD).sub.3 hybrid imaging allows for the in vivo assessment of [alpha].sub.v ß.sub.3 -integrin expression as biomarker of anti-angiogenic therapy effects in experimental breast cancer.