Chemical exchange saturation transfer for detection of antiretroviral drugs in brain tissue.

OBJECTIVE

Antiretroviral drug theranostics facilitates the monitoring of biodistribution and efficacy of therapies designed to target HIV type-1 (HIV-1) reservoirs. To this end, we have now deployed intrinsic drug chemical exchange saturation transfer (CEST) contrasts to detect antiretroviral drugs within the central nervous system (CNS).

DESIGN AND METHODS

CEST effects for lamivudine (3TC) and emtricitabine (FTC) were measured by asymmetric magnetization transfer ratio analyses. The biodistribution of 3TC in different brain sub-regions of C57BL/6 mice treated with lipopolysaccharides was determined using MRI. CEST effects of 3TC protons were quantitated by Lorentzian fitting analysis. 3TC levels in plasma and brain regions were measured using ultraperformance liquid chromatography tandem mass spectrometry to affirm the CEST test results.

RESULTS

CEST effects of the hydroxyl and amino protons in 3TC and FTC linearly correlated to drug concentrations. 3TC was successfully detected in vivo in brain sub-regions by MRI. The imaging results were validated by measurements of CNS drug concentrations.

CONCLUSION

CEST contrasts can be used to detect antiretroviral drugs using MRI. Such detection can be used to assess spatial--temporal drug biodistribution. This is most notable within the CNS where drug biodistribution may be more limited with the final goal of better understanding antiretroviral drug-associated efficacy and potential toxicity.