# Immuno-PET for Glioma Imaging: An Update
## 4 Targets for Immuno-PET
### Cell Differentiation Antigens  
CD146 is a key biomarker in cancer that was first discovered in 1987 in metastatic lesions and advanced original melanoma, with infrequent detection in benign lesions, and was dubbed \"MIC18\". CD146's principal functions are associated with intercellular and cell-matrix adhesion [43]. Nonetheless, its involvement in a variety of other processes, including development, cell motility, signal transmission, stem cell differentiation, immunological response, angiogenesis, and, more recently, the onset of epithelial-mesenchymal transition, has been documented. [PERSON] et al. developed YY146, an mAb -targeting human CD146, using a novel approach for noninvasive CD146 imaging in GBM mice [44]. Their research also studied CD146's correlation with tumor traits and used a unique immunization approach, identifying YY146 as the top CD146-binding clone, especially in CD146-overexpressingmelanoma cells. They compared CD146 levels in U87 MG and U251 GBM cell lines, showing higher CD146 expression in U87 MG cells. In vivo, immuno-Pet with [64 Cu]-NOTA-YY146 effectively located CD146-overexpressing U87 MG tumors, with high-contrast PET imaging. Blocking studies confirmed specificity, and biodistribution studies and immunofluorescence validated uptake. Of note, CD146-positive staining correlated with high tumor grade, highlighting [64 Cu]-NOTA-YY146's potential for use in GBM detection and targeted therapy. The antibody YY146 was subsequently labeled with the 89 Zr radionuclide, known for its longer half-life (t1/2: 78.4 h), aiding in distribution and kinetics studies. [PERSON] and colleagues synthesized [89 Zr]-Df-YY146, a new mAb for imaging CD146 expression in GBM mouse models via noninvasive immuno-PET [45]. YY146 was linked to deferoxamine (Df) for 89 Zr labeling. In vitro assays on two different cell lines, U87 MG and U251 GBM, defined CD146 levels. The CD146-binding affinities of YY146 and Df-YY146 were compared (5%), and their activity was 44 GBq/mol. Longitudinal PET revealed significant and persistent U87 MG absorption (14.00 3.28%ID/g at 48 h p.i.). U251 tumors, on the other hand, displayed lesser uptake (5.15 0.99%ID/g at 48 h p.i.) due to lower CD146 expression. CD146-specificity was confirmed by a competitive inhibition experiment that prevented U87 MG absorption. PET data from biodistribution were confirmed, and histological investigation associated tracer uptake with CD146 expression. Notably, [89 Zr]-Df-YY146 exhibited significant and specific uptake in brain tumors, highlighting its potential for use in the noninvasive PET imaging of CD146 expression. In future clinical applications, this might guide interventions and assess responses to CD146-targeted therapies. In recent years, immunoevasion has emerged as one of the most significant mechanisms underlying tumor growth and proliferation. This is especially important in the setting of GBM, where tumor-associated myeloid cells (TAMCs) account for roughly 40% of the tumor mass. TAMCs play a pivotal role not only in disease progression, but also in therapy resistance, making them promising targets for therapeutic interventions [46; 47]. Therefore, it is imperative to develop imaging and molecular biomarkers capable of detecting and monitoring TAMCs. [PERSON] et al. devised a novel approach by conjugating a human/mouse cross-reactive anti-CD11b antibody with desferrioxamine, incorporating 89 Zr for the purpose of detecting TAMC infiltration in GBM models [48]. Immuno-PET imaging was conducted, with and without the administration of a blocking dose of anti-CD11b antibody, 72 h after injecting [89 Zr]-anti-CD11b antibody into mice bearing orthotopic syngeneic GL261 gliomas, as well as in non-tumor-bearing mice. Significantly, increased tracer uptake was observed at tumor sites compared to the contralateral brain hemisphere. Notably, the use of a radiocompound with a 10-fold lower specific activity for blocking substantially reduced the SUV in tumor xenografts, providing compelling evidence of binding specificity.