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Illustration showing binding mechanism and associated signaling pathways of PET agents that become bound to receptors / transporters. See also main text. The grey box represents the cytoplasm, while the yellow and blue boxes represent mitochondria and nucleus, respectively. Green arrows represent binding of specific PET agent, while black arrows represent signaling pathway of receptor. Red text / arrows show brain tumor cell-specific alterations. Not shown for the sake of clarity: positive effect of adenosine / adenosine receptor pathway on tumor invasion and migration, as well as on suppressing immune reaction to the tumor.
Abbreviations: A₁AR, adenosine A₁ receptor; A_2AAR, adenosine A_2A receptor; AKT, protein kinase B; AQP, aquaporin; ARF, ADP ribosylation factor; ATRX, alpha-thalassemia / mental retardation syndrome X; CXCR4, C-X-C motif chemokine receptor 4; CXCL12, C-X-C motif chemokine ligand 12; EGF, epidermal growth factor and EGFR, its receptor; EMT, epithelial-mesenchymal transition; FAP, fibroblast activation protein; GLUT, glucose transporter; GRP, gastrin releasing peptide and GRPR, its receptor; MAPK, mitogen-activated protein kinase; MDM, E3 ubiquitin-protein ligase; MGMT, O⁶-methylguanine-DNA-methyltransferase; MMP, matrix metalloproteinase; mTORC, mechanistic target of rapamycin complex 1; NFκB, nuclear factor kappa-B; PI3K, phosphatidylinositol 3-kinase; PSMA, prostate-specific membrane antigen; PTEN, phosphatase and tensin homolog; Rb, retinoblastoma protein; ROS, reactive oxygen species; SSTR, somatostatin receptor; TERT, telomerase reverse transcriptase; TNF-α, tumor necrosis factor alpha; TSPO, translocator protein; VEGF, vascular endothelial growth factor and VEGFR, its receptor.

Simplified illustration of key metabolic and regulatory pathways that can be impaired, inhibited or upregulated in tumor cells, including the associated PET agents. The grey box represents the cytoplasm, while the yellow and blue boxes represent mitochondria and nucleus, respectively. Main results of the different pathways are highlighted by red boxes (e.g., increased protein synthesis). Red texts indicate oncogenic or tumoral changes influencing the illustrated pathways. Green texts indicate PET agents. Orange lines (both solid and dashed, different for clarity only) represent upregulated pathways, while normal interactions that are nonetheless relevant for the illustration are shown as black (solid or dashed) lines. The lipid raft (dashed box) was randomly placed, merely illustrating its function of clustering proteins and associated signaling pathways. Dark blue and light blue boxes crossing the plasma membrane represent resp. transporters and receptors.
Abbreviations: 2HG, 2-hydroxyglutarate; A₁AR, A₁ adenosine receptor; A_2AAR, A_2A adenosine receptor; ACSS, acyl coenzyme A synthetase; AKT, protein kinase B; AQP, aquaporin; ARF, ADP ribosylation factor; ATP, adenosine triphosphate; ATRX, alpha thalassemia / mental retardation syndrome X-linked; BRAF, B-Raf proto-oncogene; CHT1, high-affinity choline transporter; CKα, choline kinase alpha; CoA, acyl coenzyme A; COX, cyclooxygenase; CTL, choline transporter-like protein; Ctr1, copper transporter 1; CXCR4, C-X-C motif chemokine receptor 4 and its ligand CXCL12, C-X-C motif chemokine ligand; DAT, dopamine active transporter; DNA, deoxyribonucleic acid; EGF, epidermal growth factor and EGFR, its receptor; EMT, epithelial-mesenchymal transition; ENT, equilibrative nucleoside transporter; EP, prostaglandin E2 receptor; ERK, extracellular signal-regulated kinases; FAP, fibroblast activation protein; G6P, glucose-6-phosphate; GRP, gastrin releasing peptide and GRPR, its receptor; HIF, hypoxia-inducible factors; IDH, isocitrate dehydrogenase; IDO, indoleamine 2,3-dioxygenase; LDH, lactate dehydrogenase; MAPK, mitogen-activated protein kinase; MCT, monocarboxylate transporter; MDM, E3 ubiquitin-protein ligase; MGMT, O⁶-methylguanine-DNA-methyltransferase; MMP, matrix metalloproteinase; mTORC, mechanistic target of rapamycin complex 1; NFκB, nuclear factor kappa-B; NF, neurofibromatosis; PDGF, platelet-derived growth factor; PGE₂, prostaglandin E2; PI3K, phosphatidylinositol 3-kinase; PKM2, pyruvate kinase M2; PS, phosphatidylserine; PSMA, prostate-specific membrane antigen; PTEN, phosphatase and tensin homolog; Rb, retinoblastoma protein; ROS, reactive oxygen species; SMCT, Na⁺ monocarboxylate cotransporter; SSTR, somatostatin receptor; TCA, tricarboxylic acid; TERT, telomerase reverse transcriptase; Tf, transferrin; TFRC, transferrin receptor; TGF-β, transforming growth factor beta; TNF-α, tumor necrosis factor alpha; TSPO, translocator protein; VEGF, vascular endothelial growth factor and VEGFR, its receptor.