Oncologic PET Radiotracers and Their Mechanisms of Uptake in Cancer

RadiotracerMeasures or targetsUptake mechanismMain indications studiedAvailability
18F-FDGGlucose metabolism (indirect)Is taken up via GLUT1 and phosphorylation by hexokinaseVarious cancersWidely, routine
SSTASomatostatin receptorsBinds mainly to subtype 2 and in lesser degree to subtypes 3 and 5Well- and moderately differentiated NETsIncreasing
68Ga-PSMACellular PSMABinds to cellular PSMA and internalizesProstate cancerIncreasing
18F-NaFOsteoblastic activityExchanges 18F ions with hydroxyl ions on surface of hydroxyapatite to form fluoroapatiteBone metastases from various cancersIncreasing
18F-FLTCellular proliferation (indirect)Is phosphorylated by thymidine kinase (not incorporated into DNA)Various cancers; NSCLC, lymphomasLimited
18F-FETAA uptake by transportersEnters cells by LAT1Brain tumors, particularly gliomasLimited
11C-METAA uptake and protein synthesisEnters cells by LAT1 and is involved in synthesis of proteins and phospholipidsBrain tumors, particularly gliomasLimited
18F-FLUCAA uptake by transportersEnter cells by AA transporter ASCT2 and LAT1Prostate cancerLimited
18F-DOPA18F-DOPA transport, storage, and metabolismEnters neuroendocrine cells by LAT1, is converted to dopamine by AA decarboxylase, and is trapped in vesicles via VMATNETs, pheo, neuroblastoma, PG, gliomasLimited
11C-choline and 18F-fluorocholineCell membrane synthesis or cellular proliferationIs phosphorylated by choline kinase to phosphocholine and converted to phosphatidylcholineProstate cancerLimited
11C-acetateCellular proliferationIncorporates into cellular membraneHCC (well-differentiated), renal cancersLimited
68Ga-FAPICancer-associated fibroblastsBinds to fibroblast activation protein on cancer-associated fibroblastsVarious cancersLimited
18F-FESEstrogen receptorBinds to estrogen receptorBreast cancer, ovarian cancerLimited
89Zr-trastuzumabHuman epidermal growth factorBinds to human epidermal growth factorBreast cancerLimited
18F-FDHTAndrogen receptorBinds to androgen receptorProstate cancerLimited
124IIodine metabolismIs taken up by thyroid follicular cells via Na+/I− symporter, is oxidized by thyroid peroxidase, stays in colloid, or leaves as thyroid hormonesWell-differentiated thyroid cancerLimited
124I-MIBGNorepinephrine transporterIs taken up by sympathicomedullary tissue via norepinephrine transporter (uptake-1 system) and stored in neurosecretory granulesPheo, neuroblastoma, PGLimited
18F-FMISOHypoxiaNitro-group undergoes reduction in hypoxia, forms highly reactive oxygen radicals, and binds to intracellular macromoleculesVarious cancers, particularly brain and HNLimited
64Cu-ATSMHypoxiaAccumulates in regions with higher CD133+ expression and activates hypoxia inducible factor 1 (possible mechanisms)Various cancers, particularly brain and HNLimited
Folate*Folate receptor αBinds to folate receptor-αVarious cancersLimited
68Ga-pentixaforCXC motif chemokine receptor 4Binds to CXC motif chemokine receptor 4Various cancersLimited
11C-lactateLactate metabolismUndergoes oxidative phosphorylationVarious cancersLimited
Immuno-PET*Tumor-associated antigensMonoclonal antibodies bind to tumor-associated antigensVarious cancersLimited
  • * Various radiotracers.

  • GLUT1 = glucose transporter 1; SSTA = 68Ga-SSTAs (somatostatin analogs); NET = neuroendocrine tumor; FLT = fluorothymidine; NSCLC = non–small cell lung carcinoma; FET = fluoroethyltyrosine; AA = amino acid; LAT1 = L-type amino acid transporter; MET = methionine; FLUC = fluciclovine; ASCT2 = alanine, serine, cysteine transporter 2; 18F-DOPA = 6-18F-fluoro-l-dopa; VMAT = volumetric modulated arc therapy; pheo = pheochromocytoma; PG = paraganglioma; HCC = hepatocellular carcinoma; FAPI = fibroblast-activation-protein inhibitor; FES = fluoroestradiol; FDHT = fluorodihydrotestosterone; MIBG = metaiodobenzylguanidine; FMISO = fluoromisonidazole; ATSM = diacetyl-bis(N4-methythiosemicarbazone); HN = head and neck.