PT - JOURNAL ARTICLE AU - Azari, Feredun AU - Zhang, Kevin AU - Kennedy, Gregory T. AU - Chang, Ashley AU - Nadeem, Bilal AU - Delikatny, Edward J. AU - Singhal, Sunil TI - State of the Art: Precision Surgery Guided by Intraoperative Molecular Imaging AID - 10.2967/jnumed.121.263409 DP - 2022 Aug 01 TA - Journal of Nuclear Medicine PG - jnumed.121.263409 4099 - http://jnm.snmjournals.org/content/early/2022/08/11/jnumed.121.263409.short 4100 - http://jnm.snmjournals.org/content/early/2022/08/11/jnumed.121.263409.full AB - Intraoperative molecular imaging (IMI) has recently emerged as an important tool in the armamentarium of surgical oncologists. IMI allows real-time assessment of oncologic resection quality, margin assessment, and occult disease detection during real-time surgery. Numerous tracers have now been developed for use in IMI guided tissue sampling. Fluorochromes localize to the tumor by taking advantage of their disorganized capillary milieu, overexpressed receptors, or upregulated enzymes. Although fluorescent tracers can suffer from issues of autofluorescence and lack of depth penetration, these challenges are being addressed through hybrid radioactive/fluorescent tracers and new tracers that fluoresce in the NIR-II range. IMI is already being utilized to treat numerous cancers, with demonstrated improvement in cancer recurrence and patient outcomes without incurring significant burden on either clinicians or patients. In this comprehensive review, we discuss history, mechanism, current oncologic applications, and future directions of IMI guided optical biopsy.