TY - JOUR T1 - Combined PARP1-targeted nuclear contrast and reflectance contrast enhances confocal microscopic detection of basal cell carcinoma JF - Journal of Nuclear Medicine JO - J Nucl Med DO - 10.2967/jnumed.121.262600 SP - jnumed.121.262600 AU - Aditi Sahu AU - Jose Cordero AU - Xiancheng Wu AU - Susanne Kossatz AU - Ucalene Harris AU - Paula Demetrio Desouza Franca AU - Nicholas R Kurtansky AU - Niasia Everett AU - Stephen Dusza AU - Jilliana Monnier AU - Piyush Kumar AU - Christi Alessi-Fox AU - Christian Brand AU - Sheryl Roberts AU - Kivanc Kose AU - William Phillip AU - Erica Lee AU - Chih-Shan Jason Chen AU - Anthony Rossi AU - Kishwer Nehal AU - Melissa Pulitzer AU - Caterina Longo AU - Allan Halpern AU - Thomas Reiner AU - Milind Rajadhyaksha AU - Manu Jain Y1 - 2021/10/01 UR - http://jnm.snmjournals.org/content/early/2021/10/14/jnumed.121.262600.abstract N2 - 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 impose a fundamental limit on contrast, detectability, and diagnostic accuracy. We investigated PARPi-FL, an exogenous nuclear poly (ADP-ribose) polymerase (PARP1)-targeted fluorescent contrast agent and fluorescence confocal microscopy (FCM) towards 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. Diagnostic accuracy of PARPi-FL contrast was evaluated in 83 surgical specimens. Optimal parameters for trans-epidermal 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, as compared to normal skin structures. Blinded reading of RCM-and-FCM images by two experts demonstrated a higher diagnostic accuracy for BCCs with combined fluorescence and reflectance contrast, as compared to RCM-alone. Optimal parameters (time and concentration) for PARPi-FL trans-epidermal permeation through intact skin were successfully determined. Conclusion: Combined fluorescence and reflectance contrast may improve noninvasive BCC diagnosis with confocal microscopy. ER -