TY - JOUR T1 - Combined PARP1-Targeted Nuclear Contrast and Reflectance Contrast Enhance Confocal Microscopic Detection of Basal Cell Carcinoma JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 912 LP - 918 DO - 10.2967/jnumed.121.262600 VL - 63 IS - 6 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 Fox AU - Christian Brand AU - Sheryl Roberts AU - Kivanc Kose AU - William Phillips 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 - 2022/06/01 UR - http://jnm.snmjournals.org/content/63/6/912.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 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. ER -