< Terug naar vorige pagina

Publicatie

Evaluation of [$^{18}F$]CP18 as a substrate-based apoptosis imaging agent for the assessment of early treatment response in oncology

Tijdschriftbijdrage - Tijdschriftartikel

The substrate-based positron emission tomography (PET) tracer [18F]CP18 is capable of detecting the activity of caspase-3/7, two key executioner proteases in the apoptosis pathway, through selective cleavage of the ligand by the activated proteases and subsequent accumulation in apoptotic cells. Using an in vitro and in vivo model of colorectal cancer (CRC), we investigated whether [18F]CP18 tracer accumulation provides a measure for apoptosis and reliably reflects early treatment response to chemotherapeutics. Procedures [18F]CP18 cell uptake was assessed in treated Colo205 cells (saline, 5-fluorouracil (5-FU), irinotecan or their combination) and correlated with caspase-3/7 activity. [18F]CP18 imaging was performed in Colo205 xenografts, starting with a baseline μPET/micro X-ray computed tomography (​μCT) scan, followed by a 3-day treatment with saline (n = 5), 5-FU (low sensitivity, n = 4), irinotecan (high sensitivity, n = 5), or a combination of both (n = 7). The study was concluded with a second [18F]CP18 scan, 24 h after final treatment administration, followed by tumor removal for gamma counting (%ID/g) and for cleaved caspase-3 immunohistochemistry (apoptotic index/necrosis). Tumors were delineated on μCT images and, using the obtained volumes of interest, average percentage injected dose per cubic centimeter (%ID/cm3) was calculated from every μPET image. Results In vitro, [18F]CP18 cell uptake was positively correlated with caspase-3/7 activity (r = 0.59, p = 0.003). A drug-dependent increase in [18F]CP18 tumor uptake compared to baseline was observed in animals treated with 5-FU (+14 ± 25 %), irinotecan (+56 ± 54 %), and their combination (+158 ± 69 %, p = 0.002). %ID/cm3 showed a positive relationship with both %ID/g (r = 0.83, p < 0.0001) and the apoptotic index (r = 0.60, p = 0.004), but not with tumor necrosis (r = 0.22, p = 0.36). Conclusion Both our in vitro and in vivo findings have shown the ability of [18F]CP18-PET to visualize therapy-induced cancer cell apoptosis and possibly serve as a biomarker for early therapy response.
Tijdschrift: Molecular imaging and biology
ISSN: 1536-1632
Volume: 19
Pagina's: 560 - 569
Jaar van publicatie:2017
Trefwoorden:A1 Journal article
BOF-keylabel:ja
BOF-publication weight:1
CSS-citation score:1
Authors from:Higher Education
Toegankelijkheid:Open