Noninvasive assessment and therapeutic monitoring of drug-resistant colorectal cancer by MR molecular imaging of extradomain-B fibronectin.

摘要: Antineoplastic resistance represents a multifaceted challenge for cancer therapy and diagnostics. Extensive molecular heterogeneity, even within neoplasms of the same type, can elicit distinct outcomes administering therapeutic pressures, frequently leading to development drug-resistant populations. Improved success oncotherapies merits exploration precise imaging technologies that detect not only anatomical but also changes in tumors their microenvironment, early on treatment regimen. To this end, we developed magnetic resonance (MRMI) strategies target extracellular matrix oncoprotein, extradomain-B fibronectin (EDB-FN), non-invasive assessment monitoring colorectal (CRC). Methods: Two CRC lines generated from parent DLD-1 RKO cells by long-term with 5'-FU plus CB-839 respectively, were characterized functional gene expression using 3D culture, transwell invasion, qRT-PCR, western blot assays. Contrast-enhanced MRMI EDB-FN was performed athymic nu/nu mice bearing subcutaneous tumor xenografts 40 µmol/kg dose macrocyclic ZD2-targeted contrast agent MT218 [ZD2-N3-Gd (HP-DO3A)] 3T MRS 3000 scanner. Immunohistochemistry conducted patient specimens anti-EDB-FN antibody G4. Results: Analyses TCGA GTEx databases revealed poor prognosis colon patients higher levels EDB-FN. Similarly, immunohistochemical staining showed increased primary adenocarcinoma hepatic metastases, none normal adjacent tissues. Drug-resistant DLD1-DR RKO-DR found demonstrate enhanced invasive potential significantly elevated over counterparts. (60% lower than clinical dose) resulted robust signal enhancement 84-120% increase contrast-to-noise ratios (CNRs) non-resistant The feasibility evaluated treated pan-AKT inhibitor MK2206-HCl. failed respond therapy, which accurately detected MT218, demonstrating CNRs 4-week follow-up scans pre-treatment scans. Conclusions: is promising marker assessing drug resistance. at reduced facilitate effective response CRC, highlighting its translational active surveillance management other malignancies.