Dual-Peak Lorentzian CEST MRI for antiretroviral drug brain distribution

Abstract

Objectives Spatial–temporal biodistribution of antiretroviral drugs (ARVs) can now be achieved using MRI by utilizing chemical exchange saturation transfer (CEST) contrasts. However, the presence of biomolecules in tissue limits the specificity of current CEST methods. To overcome this limitation, a Lorentzian line-shape fitting algorithm was developed that simultaneously fits CEST peaks of ARV protons on its Z-spectrum. Case presentation This algorithm was tested on the common first line ARV, lamivudine (3TC), that has two peaks resulting from amino (–NH2) and hydroxyl (–OH) protons in 3TC. The developed dual-peak Lorentzian function fitted these two peaks simultaneously, and used the ratio of –NH2 and –OH CEST contrasts as a constraint parameter to measure 3TC presence in brains of drug-treated mice. 3TC biodistribution calculated using the new algorithm was compared against actual drug levels measured using UPLC-MS/MS. In comparison to the method that employs the –NH2 CEST peak only, the dual-peak Lorentzian fitting algorithm showed stronger correlation with brain tissue 3TC levels, signifying estimation of actual drug levels. Conclusions We concluded that 3TC levels can be extracted from confounding CEST effects of tissue biomolecules resulting in improved specificity for drug mapping. This algorithm can be expanded to measure a variety of ARVs using CEST MRI.