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. 2022 Sep 22;10(9):e004902. doi: 10.1136/jitc-2022-004902

Table 1.

Seminal preclinical nuclear-based, MRI and ultrasound studies employing direct and indirect molecular imaging for the in vivo monitoring of T cell-based immunotherapies and their immune-related components

Immune
Cell		 Molecular
Target		 Imaging
agent		 Labeling
approach		 Reporter
Gene		 Imaging modality Ref
T lymphocyte n/a 89Zr-oxine Direct n/a PET 15
T lymphocyte n/a 111In-oxine Direct n/a SPECT 16
T lymphocyte n/a 18F]MFBG and(123I/124I)MIBG, 124I, 18F-FEAU, 124I-FIAU Indirect hNET, hNIS, dCKDM, HSV1-tk PET 26
T lymphocyte n/a 124I scFv antibody fragment Indirect CEA N-A3 PET 23
T lymphocyte n/a 124I-FIAU Indirect HSV1-tk, GFP PET 43
T lymphocyte Pan-ErbB CAR (18F)BF4- Indirect hNIS PET 27
T lymphocyte CD19 CAR (18F)DCFPyL Indirect tPSMA(N9del) PET 28
T lymphocyte GD2 CAR (18F)TMP Indirect eDHFR PET 29
T lymphocyte CD19 CAR 86Y-AABD Indirect DAbR1 PET 30
T lymphocyte EGFRvIII CAR 19F-PFC Direct n/a MRI 75
T lymphocyte CD19 CAR n/a Indirect Heat-inducible-GFP-PGK-mCherry MRI-guided FUS 8
T lymphocyte OX40 64Cu-DOTA-AbOX40 Direct n/a PET 77
T lymphocyte ICOS 89Zr-DFO-ICOS Direct n/a PET 76
T lymphocyte IL-2 (18F)FB-IL-2 Direct n/a PET 78
T lymphocyte TCR 64Cu-DOTA-KJ1-26 Direct n/a PET 79
T lymphocyte CD3 89Zr-DFO-CD3 Direct n/a PET 80 81
T lymphocyte CD4 89Zr-GK1.5 cDb Direct n/a PET 82
T lymphocyte CD8 89Zr- malDFO-169 cDb and 64Cu-169 cDb Direct n/a PET 38 83
T lymphocyte CD4/CD8 (123I)MIBG/(124I)FIAU Indirect hNET/ HSV1-tk SPECT/
PET		 22
T lymphocyte CD8 SPIO Direct n/a MRI 84
T lymphocyte Granzyme B 68Ga-NOTA-GZP Direct n/a PET 41
T lymphocyte IFN-gamma 89Zr- IFN-gamma Direct n/a PET 42
T lymphocyte n/a (phosphorylated by TK1) (18F)FLT Direct n/a PET 54 62
T lymphocyte dGK (18F)F-AraG Direct n/a PET 85
T lymphocyte dCK (18F)CFA,(18F)FAC,(18F)FACB Direct n/a PET 86 87
T lymphocyte PD-1 64Cu- PD-1, 64Cu-DOTA- PD-1, 64Cu-NOTA-PD-1, 89Zr-Df-Pembrolizumab, 89Zr-Df-Nivolumab Direct n/a PET 47 48 88 89
T lymphocyte PD-L1 99mTc, 111In,
111In-DTPA,
89Zr-DFO, 64Cu,
64Cu-DOTA,
68Ga-NOTA,
18F-BMS-986192		 DIrect n/a SPECT/PET 36 46 50 51
T lymphocyte CTLA-4 64Cu-DOTA- and NOTA-Ipilimumab Direct n/a PET 52 53
T lymphocyte LAG-3 99mTcO4-,
89Zr-REGN3767		 Direct n/a SPECT,
PET		 55 56
T lymphocyte TIM-3 64Cu-NOTA-RTM3-23 Direct n/a PET 57
T lymphocyte TIGIT 89Zr- and 64Cu-AB154 Direct n/a PET 58
Treg n/a 99mTcO4- Indirect hNIS SPECT 33
Treg IL-10-HLA-A2 CAR 99mTcO4- Indirect hNIS SPECT 34
Gamma delta T lymphocyte n/a 89Zr-oxine Direct n/a PET 35
NK n/a 89Zr-oxine Direct n/a PET 60
NK n/a (18F)FDG Direct n/a PET 59
NK n/a 19F-PFC, 19F,
Ferumoxides/
Ferucarbotran		 Direct n/a MRI 59
DC n/a (18F)BF4- Indirect hNIS PET 65
DC n/a (phosphorylated by TK1) (18F)FLT Direct n/a PET 62
DC n/a 19F-PFC, 19F, SPIO Direct n/a MRI 61 64
DC n/a n/a Indirect Ferritin MRI 66
Macrophages n/a SPION ferumoxytol Direct n/a MRI 67
Monocytes/
macrophages		 CD40 89Zr-TRAF6i-HDL Direct n/a PET 90
Monocytes n/a 19F-PFC Direct n/a MRI 68

BI, Boehringer Ingelheim; BMS, Bristol-Myers Squibb; CAR, chimeric antigen receptor; CEA, carcinoembryonic antigen; DC, dendritic cell; dCK, Deoxycytidine kinase; Df or DFO, Deferoxamine; dGK, Deoxyguanosine; DOTA, 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid; eDHFR, Escherichia Coli dyhydrofolate reductase; EGFRvIII, Epidermal Growth Factor Receptor variant III; [18F]BF4, Tetrafluoroborate; [18F]CFA, [18F]Clorafabine; [18F]DCFPyL, Piflufolastat fluorine 18F; [18F]FAC, 1-(2’-deoxy-2’-18F-fluoroarabino-furanosyl) cytosine; [18F]F-AraG, 2’-deoxy-2’-18F-fluoro-9β-D-arabinofuranosyl-guanine; [18F]FB-IL-2, N-(4-18F fluorobenzoyl_interleukin-2; [18F]FDG, [18F]fluorodeoxyglucose; [18F]FHBG, 9-(4-(18)F-Fluoro 3[hydroxymethyl]butyl)guanine; [18F]FIAU, 2’-deoxy-2’-[18F]-fluoro-1-beta-D-arabinofuranosyl-5-iodouracil; [18F]FLT, [18F]fluorothymidine; (18F)TMP, (18F)fluoropropyl-trimethoprin; FUS, Focused Ultrasound; 68Ga-NOTA-hGZP, 68Gallium-1,4,7-Triazacyclononane-1,4,7-triacetic acid-human biotin βAla-GGG-IEPD-CHO; GRm13Z40, Interleukin-13 zetakine Receptor Alpha 2-targeted CAR; hNET, human norepinephrine transporter; hNIS, human sodium iodide symporter; [124I]FIAU, 124I-2’-fluoro-deoxy-1-beta-D-arabinofuranosyl-5-iodouracil; [123I]MIBG, [123I]metaiodobenzylguanidine; n/a, not available; NK, natural killer; PET, positron emission tomography; PFC, Perfluorocarbon; P28z, PSMA-targeted CD28z CAR; SPECT, single photon emission computed tomography; SPION, superparamagnetic iron oxide nanoparticle; TRAF6, tumor necrosis factor receptor-associated factor 6; 86Y-AABD, 86Yttrium (S)-2-(4-acrylamidobenzyl)-DOTA.