. 2022 Apr 13;128(14):2704–2716. doi: 10.1002/cncr.34228

TABLE 1.

PET Molecular Imaging to Study Cancer Hallmarks

Hallmarks	Studied Aspects	Imaging Targets ^a	PET Imaging Tools ^a	References
Sustaining proliferative signaling	Signaling	EGFR	⁸⁹Zr‐cetuximab, ⁸⁹Zr‐panitumumab, ⁸⁹Zr‐nimotuzumab	12, 13
Sustaining proliferative signaling	Signaling	PI3K	¹⁸F‐FMTA‐2, ¹¹C‐pictilisib and ¹⁸F‐PEG3‐GDC‐0941	14
Evading growth suppressors	Specific gene	P53	p53‐TKGFP system, p53‐TAg‐TK‐GFP system	15, 16
Evading growth suppressors	Transduction pathway	TGF‐β	⁸⁹Zr‐fresolimumab, ⁶⁴Cu‐NOTA‐TRC105	17, 18
Resisting cell death	Apoptosis	Phosphatidylserine exposure	¹⁸F‐annexin V, ¹⁸F‐FBAM, ¹⁸F‐C2Am	19
		Apoptotic membrane imprint	¹⁸F‐ML‐10	20
		Caspase	¹⁸F‐ICMT‐11, ¹⁸F‐CP18, caspase‐3‐cTK system	21, 22, 23
Enabling replicative immortality	Telomerase function	hTERT	hTERT‐reporter systems, radiolabeled ASON, radiolabeled siRNA, ⁶⁴Cu‐hTERT IgM	24, 25, 26, 27, 28
Enabling replicative immortality	Telomerase function	hTR	hTR‐NIS system	24
Inducing angiogenesis	Direct angiogenetic processes	VEGF/VEGFR	¹⁸F‐AlF‐NODA‐scVR1, ⁸⁹Zr‐bevacizumab, ⁸⁹Zr‐ranibizumab, ¹¹C‐erlotinib	29, 30
	Direct angiogenetic processes	Integrin	¹⁸F‐galacto‐RGD, ¹⁸F‐fluciclatide, ¹⁸F‐RGD‐K5, and ⁶⁸Ga‐NOTA‐RGD	31
	Indirect angiogenetic state	Hypoxia	¹⁸F‐FMISO, ¹⁸F‐FAZA, ¹⁸F‐HX4, and ⁶⁴Cu‐ATSM	32, 33, 34, 35
Activating invasion and metastasis	Metastasis‐initiating processes	CSCs	⁶⁴Cu‐NOTA‐AC133 mAb, ⁶⁴Cu‐T140‐2D	36, 37
	Metastasis‐initiating processes	Cancer dormancy	¹⁸F‐NFTG	38
	Phenotypic plasticity	EMT and MET	¹¹C‐SU11274	39
Genome instability and mutation	DNA damage	Single‐strand break	¹⁸F‐FTT and ¹⁸F‐PARPi	40, 41
	DNA damage	Double‐strand break	⁸⁹Zr‐anti‐γH2AX‐TAT	42
	Gene mutation	Nucleic acid	Radiolabeled ASON	43
Tumor‐promoting inflammation	Cellular components of tumor microenvironment	Macrophages	⁶⁸Ga‐pentixafor, ⁶⁴Cu‐MAN‐LIPs, 3′‐Aza‐2′‐[¹⁸F]fluorofolic acid, ¹⁸F‐FDR‐NOC, ¹¹C‐AM7, ⁶⁴Cu‐DOTA‐DAPTA	44, 45
	Enzymes of tumor microenvironment	MMPs	⁶⁴Cu‐DOTA‐CTT, ¹⁸F‐CGS27023A	46, 47
	Enzymes of tumor microenvironment	COX‐2	¹⁸F‐desbromo‐Dup‐697, ¹⁸F‐SC58125, ¹¹C‐celecoxib, and ¹¹C‐rofecoxib	48
Reprogramming energy metabolism	Glucose metabolism	Glucose	¹⁸F‐FDG	49
	Amino acid metabolism	Various amino acids	¹¹C‐MET, ¹⁸F‐FET, ¹⁸F‐DOPA, ¹⁸F‐FGln, ¹¹C‐glutamine,	50
	Metabolism of other nutrients	Fatty acids, choline, etc.	¹¹C‐acetate, ¹¹C‐choline, ¹⁸F‐choline, ¹⁸F‐fluoroethylcholine	51, 52
Evading immune destruction	Immune cell infiltration	CD8+ T cell	⁸⁹Zr‐DFO‐CD3, ⁸⁹Zr‐malDFO‐GK1.5 cDb, ⁸⁹Zr‐Df‐IAB22M2C	53
	Cancer checkpoint	PD‐1, PD‐L1, and CTLA‐4	⁶⁴Cu‐NOTA‐PD‐1 mAb, ⁸⁹Zr‐Df‐nivolumab, ⁶⁴Cu‐NOTA‐PD‐L1 mAb, ⁶⁴Cu‐DOTA‐anti‐CTLA‐4, ⁶⁴Cu‐DOTA‐ipilimumab	54, 55, 56
	Other tumor‐associated immune cells	TAM, MDSC, neutrophils, natural killer cell, etc.	Radiopharmaceuticals targeting macrophages, ⁶⁴Cu‐NOTA‐αCD11b‐mAb, ¹⁸F‐MAPP, ⁸⁹Zr‐NKp30Ab	57, 58, 59

Abbreviations: ASON, antisense oligonucleotide; COX‐2, cyclooxygenase‐2; CSCs, cancer stem cells; CTLA‐4, cytotoxic T‐lymphocyte‐associated antigen 4; EGFR, epidermal growth factor receptor; EMT, epithelial‐to‐mesenchymal transition; hTERT, human telomerase reverse transcriptase; hTR, human telomerase RNA; IgM, immunoglobulin M; mAb, monoclonal antibody; MDSC, myeloid‐derived suppressor cells; MET, mesenchymal‐to‐epithelial transition; MMPs, matrix metalloproteinases; PD‐1, programmed cell death protein 1; PD‐L1, programmed death‐ligand 1; PET, positron emission tomography; PI3K, phosphoinositide 3‐kinase; TAM, tumor associated macrophages; TGF‐β, transforming growth factor β; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor.

^{^a}

Examples of imaging targets and corresponding PET imaging tools.