Imaging the DNA Alkylator Melphalan by CEST MRI: An Advanced Approach to Theranostics

• DOI: 10.1021/acs.molpharmaceut.6b00130
• Publication Date: 2016-07-11T20:55:01Z
• Authors: Ethel J. Ngen; Amnon Bar-Shir; Anna Jablonska; Guanshu Liu; Xiaolei Song; Roxana Ansari; Jeff W. M. Bulte; Miroslaw Janowski; Monica Pearl; Piotr Walczak; Assaf A. Gilad
• Keywords: Melphalan

Brain tumors are among the most lethal types of tumors. Therapeutic response variability and failure in patients have been attributed to several factors, including inadequate drug delivery due blood-brain barrier (BBB). Consequently, strategies being developed for local targeted drugs brain These could benefit from new approaches monitor Here, we evaluated feasibility imaging 4-[bis(2-chloroethyl)amino]-l-phenylalanine (melphalan), a clinically used DNA alkylating agent, using chemical exchange saturation transfer magnetic resonance (CEST MRI), theranostic applications. We physicochemical parameters that affect melphalan's CEST contrast demonstrated unmodified by saturating its exchangeable amine protons. Melphalan generated signal despite reactivity an aqueous milieu. The maximum was observed at pH 6.2. This trend then therapeutic responses melphalan vitro. Upon cell death, decrease cellular ∼7.4 ∼6.4 caused amplification signal. is contrary what has reported other agents where following death results Ultimately, this method be noninvasively also validate clinically.