Feasibility of dual‐contrast fluorescence imaging of pathological breast tissues

Abstract

The combination of intravital dye, methylene blue (MB), with molecular cancer marker, pH low insertion peptide (pHLIP) conjugated with fluorescent Alexa532 (Alexa532‐pHLIP), was evaluated for enhancing contrast of pathological breast tissue ex vivo. Fresh, thick breast specimens were stained sequentially with Alexa532‐pHLIP and aqueous MB and imaged using dual‐channel fluorescence microscopy. MB and Alexa532‐pHLIP accumulated in the nuclei and cytoplasm of cancer cells, respectively. MB also stained nuclei of normal cells. Some Alexa532‐pHLIP fluorescence emission was detected from connective tissue and benign cell membranes. Overall, Alexa532‐pHLIP showed high affinity to cancer, while MB highlighted tissue morphology. The results indicate that MB and Alexa532‐pHLIP provide complementary information and show promise for the detection of breast cancer.

Aiming the magic bullet: targeted delivery of imaging and therapeutic agents to solid tumors by pHLIP peptides

“…Routes of administration have included intraperitoneal, intravenous, retro-orbital and sub-cutaneous injections. pHLIP uptake has been followed in more than 20 different animal tumor models including transgenic mouse models ( Reshetnyak et al, 2011 ; Adochite et al, 2014 ; Cruz-Monserrate et al, 2014 ; Cheng et al, 2015 ; Tapmeier et al, 2015 ) and human cancer tissue specimens ( Loja et al, 2013 ; Luo et al, 2014 ; Golijanin et al, 2016 ; Brito et al, 2020 ; Mitrou et al, 2021 ).…”