RT Journal Article
SR Electronic
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
FD Society of Nuclear Medicine
SP 912
OP 918
DO 10.2967/jnumed.121.262600
VO 63
IS 6
A1 Aditi Sahu
A1 Jose Cordero
A1 Xiancheng Wu
A1 Susanne Kossatz
A1 Ucalene Harris
A1 Paula Demetrio Desouza Franca
A1 Nicholas R. Kurtansky
A1 Niasia Everett
A1 Stephen Dusza
A1 Jilliana Monnier
A1 Piyush Kumar
A1 Christi Fox
A1 Christian Brand
A1 Sheryl Roberts
A1 Kivanc Kose
A1 William Phillips
A1 Erica Lee
A1 Chih-Shan Jason Chen
A1 Anthony Rossi
A1 Kishwer Nehal
A1 Melissa Pulitzer
A1 Caterina Longo
A1 Allan Halpern
A1 Thomas Reiner
A1 Milind Rajadhyaksha
A1 Manu Jain
YR 2022
UL http://jnm.snmjournals.org/content/63/6/912.abstract
AB 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.