%0 Journal Article %A Aditi Sahu %A Jose Cordero %A Xiancheng Wu %A Susanne Kossatz %A Ucalene Harris %A Paula Demetrio Desouza Franca %A Nicholas R. Kurtansky %A Niasia Everett %A Stephen Dusza %A Jilliana Monnier %A Piyush Kumar %A Christi Fox %A Christian Brand %A Sheryl Roberts %A Kivanc Kose %A William Phillips %A Erica Lee %A Chih-Shan Jason Chen %A Anthony Rossi %A Kishwer Nehal %A Melissa Pulitzer %A Caterina Longo %A Allan Halpern %A Thomas Reiner %A Milind Rajadhyaksha %A Manu Jain %T Combined PARP1-Targeted Nuclear Contrast and Reflectance Contrast Enhance Confocal Microscopic Detection of Basal Cell Carcinoma %D 2022 %R 10.2967/jnumed.121.262600 %J Journal of Nuclear Medicine %P 912-918 %V 63 %N 6 %X Reflectance confocal microscopy (RCM) with endogenous backscattered contrast can noninvasively image basal cell carcinomas (BCCs) in skin. However, BCCs present with high nuclear density, and the relatively weak backscattering from nuclei imposes a fundamental limit on contrast, detectability, and diagnostic accuracy. We investigated PARPi-FL, an exogenous nuclear poly(adenosine diphosphate ribose) polymerase (PARP1)–targeted fluorescent contrast agent, and fluorescence confocal microscopy toward improving BCC diagnosis. Methods: We tested PARP1 expression in 95 BCC tissues using immunohistochemistry, followed by PARPi-FL staining in 32 fresh surgical BCC specimens. The diagnostic accuracy of PARPi-FL contrast was evaluated in 83 surgical specimens. The optimal parameters for permeability of PARPi-FL through intact skin was tested ex vivo on 5 human skin specimens and in vivo in 3 adult Yorkshire pigs. Results: We found significantly higher PARP1 expression and PARPi-FL binding in BCCs than in normal skin structures. Blinded reading of RCM–and–fluorescence confocal microscopy images by 2 experts demonstrated a higher diagnostic accuracy for BCCs with combined fluorescence and reflectance contrast than for RCM alone. Optimal parameters (time and concentration) for PARPi-FL transepidermal permeation through intact skin were successfully determined. Conclusion: Combined fluorescence and reflectance contrast may improve noninvasive BCC diagnosis with confocal microscopy. %U https://jnm.snmjournals.org/content/jnumed/63/6/912.full.pdf