Molecular imaging is a highly beneficial tool with the capacity to improve every aspects of cancer care. It is an in vivo imaging-based characterization and measurement of the key biomolecules and molecular events that are basic to the malignant or aberrant state . Prior to the emergence of molecular imaging, a number of “gold standard” scientific approaches (such as ViziLite, VELscope, Trimira and OralCDx, etc.) aimed at oral lesion detection were fraught with inconsistencies during standard routine head and neck examinations [184–186]. However, the establishment of integrated MRI/PET has improved the consistency and effectiveness of earlier stage cancer detection . Molecular imaging such as positron emission tomography (PET) often integrated with cross sectional imaging in the form of PET/computed tomography (PET/CT), PET/magnetic resonance imaging (MRI)/MR spectroscopic imaging (MRSI), as well as optical imaging; play a vital role in cancer detection, staging and assessment of treatment response. The optical imaging is mostly performed with the radiotracer 18F-fluoro-2-deoxy-d-glucose [FDG], integrated with cross-sectional imaging in the form of PET/computed tomography (PET/CT) . PET has been said to be the leading molecular imaging approach in a clinical environment [189–191]. PET imaging methods have been successful in both staging of diverse cancers and assessment of response of tumors to therapy [192, 193]. Several authors have shown a significantly higher level of sialic acid in oral cancer patients when compared to normal patients [194–196]. The recent discovery of molecular imaging-based individualized potential molecular tumor fingerprint has facilitated a rapid and effective development of theranostic drugs for novel treatment algorithms [197, 198]. In another study, the efficacy of fluorescence imaging using topically applied lectin-fluorophore conjugates as compared to conventional tissue autofluorescence in distinguishing tumor from normal tissues was also investigated . The results revealed that the changes in glycosylation could differentiate normal from cancerous tissues in the oral cavity with high SNRs . This is potentially a non-invasive screening method for premalignant and malignant oral mucosal tumors; and as a method for defining surgical margins and monitoring cellular changes over time. To further validate this approach for oral cancer screening, in vivo testing in a larger clinical cohort is needed. Not least, Nanobodies have also been considered as highly beneficial agent in molecular imaging of cancers, due to its rapid accumulation in tumors, homogenous distribution; efficient blood clearance, high specificity, safety, high tumor signal-to-background ratios; as well as ease of conjugation to several kinds of imaging techniques .