Table 1.

An overview of the targets expressed as a result of altered TME processes and the tumor ECM, with a number of their corresponding radioligands

Source	Target	Compound	Research phase	Reference
Hypoxia	Nitroimidazole analogs	FMISO FAZA FETNIM Cu-ATSM FETA EF1/3/5 FRP170 HX4 N4-NIM	Approved Approved Clinical trial Clinical trial Preclinical Preclinical Preclinical Preclinical Preclinical	[12, 14, 15, 24]
	CAIX	cG250 cG250-F(Ab’) A3/SIP(A3) CAIX inhibitors ZCAIX:1/2/3/4	Clinical trial Preclinical Preclinical Preclinical Preclinical	[30, 31, 34, 36, 37]
	HIF-1	IPOS (m)DKOP	Preclinical Preclinical	[41, 42]
TME acidity	Low extracellular pH (6.0–7.0)	pHLIPs FDG amine Malonic acid derivatives	Clinical trial Preclinical Preclinical	[52, 53]
Metabolism	Elevated glucose uptake	FDG	Approveda	[59, 60, 62]
Extracellular matrix	TNC-A1	F16SIP (Tenarad)	Clinical trial	[64, 65]
	EDB-FN	L19 L19SIP L19(ScFv)2 AP39 FnBPA5 ZD2-NOTA NJB2	Clinical trial Clinical trial Clinical trial Preclinical Preclinical Preclinical Preclinical	[69, 73, 76, 77]
	MMPs	MMPIs Protective antigen + LFE687a	Preclinical Preclinical	[78, 84]

^aIn clinical use for tumor imaging, not for specific TME imaging