Using FDA-approved drugs as off-label fluorescent dyes for optical biopsies: from in silico design to ex vivo proof-of-concept

Abstract

Optical biopsies bring the microscope to the patient rather than the tissue to the microscope, and may complement or replace the tissue-harvesting component of the traditional biopsy process with its associated risks. In general, optical biopsies are limited by the lack of endogenous tissue contrast and the small number of clinically approved in vivo dyes. This study tests multiple FDA-approved drugs that have structural similarity to research dyes as off-label in situ fluorescent alternatives to standard ex vivo hematoxylin & eosin tissue stain. Numerous drug-dye combinations shown here may facilitate relatively safe and fast in situ or possibly in vivo staining of tissue, enabling real-time optical biopsies and other advanced microscopy technologies, which have implications for the speed and performance of tissue- and cellular-level diagnostics.

Multispectral confocal endomicroscopy in lung biopsy guidance

“…Although multiple dye combinations were evaluated as described in Ref. 10, the work presented here employed proflavine as a nuclear stain and rose bengal as a proteinaceous connective tissue stain. Multispectral imaging was done using these dyes on ex vivo human lung core-biopsy tissue samples obtained under UA IRB Protocol 1706540415, and on rat lung resected from euthanized rats under UA IACUC Protocol 16-209.…”

“…In prior work in Ref. 10, a bench top confocal microscope with three spectral channels was used to investigate different dye combinations. Although many dye combinations produced useful image contrast, proflavine and rose bengal appeared to have the fastest binding to the desired targets.…”

“…In previous work, 10 several combinations of FDA-approved fluorescent dyes were used to image ex vivo ovine lung tissue. Each combination was made from one DNA-binding dye and one protein binding dye.…”