Preclinical evaluation of molecularly targeted fluorescent probes in perfused amputated human limbs

Logan M. Bateman; Kendra A. Hebert; Jenna A. Nunziata; Samuel S. Streeter; Connor W. Barth; Lei G. Wang; Summer L. Gibbs; Eric R. Henderson

doi:10.1117/1.JBO.28.8.082802

5 January 2023 Preclinical evaluation of molecularly targeted fluorescent probes in perfused amputated human limbs

Logan M. Bateman, Kendra A. Hebert, Jenna A. Nunziata, Samuel S. Streeter, Connor W. Barth, Lei G. Wang, Summer L. Gibbs, Eric R. Henderson

Author Affiliations +

Journal of Biomedical Optics, Vol. 28, Issue 8, 082802 (January 2023). https://doi.org/10.1117/1.JBO.28.8.082802

Abstract

Significance

This first-in-kind, perfused, and amputated human limb model allows for the collection of human data in preclinical selection of lead fluorescent agents. The model facilitates more accurate selection and testing of fluorophores with human-specific physiology, such as differential uptake and signal in fat between animal and human models with zero risk to human patients. Preclinical testing using this approach may also allow for the determination of tissue toxicity, clearance time of fluorophores, and the production of harmful metabolites.

Aim

This study was conducted to determine the fluorescence intensity values and tissue specificity of a preclinical, nerve tissue targeted fluorophore, as well as the capacity of this first-in-kind model to be used for lead fluorescent agent selection in the future.

Approach

Freshly amputated human limbs were perfused for 30 min prior to in situ and ex vivo imaging of nerves with both open-field and closed-field commercial fluorescence imaging systems.

Results

In situ, open-field imaging demonstrated a signal-to-background ratio (SBR) of 4.7 when comparing the nerve with adjacent muscle tissue. Closed-field imaging demonstrated an SBR of 3.8 when the nerve was compared with adipose tissue and 4.8 when the nerve was compared with muscle.

Conclusions

This model demonstrates an opportunity for preclinical testing, evaluation, and selection of fluorophores for use in clinical trials as well as an opportunity to study peripheral pathologies in a controlled environment.

CC BY: © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 International License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

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Logan M. Bateman, Kendra A. Hebert, Jenna A. Nunziata, Samuel S. Streeter, Connor W. Barth, Lei G. Wang, Summer L. Gibbs, and Eric R. Henderson "Preclinical evaluation of molecularly targeted fluorescent probes in perfused amputated human limbs," Journal of Biomedical Optics 28(8), 082802 (5 January 2023). https://doi.org/10.1117/1.JBO.28.8.082802

Received: 26 August 2022; Accepted: 9 November 2022; Published: 5 January 2023

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