Table 2.

Summary of preclinical biological evaluation of radiolabeled CA-IX small molecule inhibitors shown in Figure 4.

Agent	Binding affinity, Ki (nM)	Model	Tumour uptake (%ID/g)*	T:B ratio	T:M ratio	Tumour visualization (Yes/No)	Ref
1a-c	0.9 (R = 3-NO2)	-	-	-	-	-	75
	5.4 (R = 4-Ac)	-	-	-	-	-
	0.3 (R = 2-CN)	-	-	-	-	-
2	124	HT-29	< 0.25 at 2 h	-	-	No	78
		U373	< 0.25 at 4 h	-	-	No
3	45	HT-29	0.83 at 1 h	< 1.0	< 1.0	No	79
4	70	HT-29	1.16 at 1 h	< 1.0	< 2.0	No	79
5a-c	9.3 (R = Me)	HT-29	0.51 at 1 h	~ 1.0	~ 1.0	No	81
	9.6 (R = Ac)		0.59 at 1 h	~ 2.0	~ 1.0	No
	9.1 (R = Cl)		0.98 at 1 h	~ 1.0	~ 1.0	No
6a-b	8.5 (n = 0)	HT-29	0.33 at 1 h	3.9	9.6	Yes	82
	35.7 (n = 2)		0.30 at 1 h	2.9	4.9	Yes
7a-b	6.6 (n = 0)	HT-29	0.64 at 1 h	1.3	2.2	Yes	82
	8.0 (n = 2)		0.56 at 1 h	1.0	3.2	Yes
8	220	HT-29	0.41 at 1 h	~ 1.0	~ 2.0	Yes	83
9	9†	-	-	-	-	-	84
10	58	HT-29	0.2 at 0.5 h	< 1.0	-	-	85
11	59	HT-29	0.2 at 0.5 h	< 1.0	-	-	86
12	66	HT-29	0.5 at 0.5 h	< 1.0	-	-	86
13‡	-	HT-29	0.1 at 0.5 h	< 1.0	-	-	86
			0.1 at 0.5 h	< 1.0	-	-
14	10.8	HT-29	0.81 at 1 h	1.3	5.0	Yes	87
15	25.4	HT-29	1.93 at 1 h	1.3	4.1	Yes	87
16	7.7	HT-29	2.30 at 1 h	2.7	4.2	Yes	87
17	63.1	HCT 116	-	2.4	-	Yes	89
18	-	SK-RC-52	22.1 at 3 h	69.9	-	Yes	90
19	108†	SK-RC-52	34.0 at 8 h	77.0	34.2	Yes	91
20	157†	SK-RC-52	19.3 at 4 h	57.7	29.4	Yes	92

*Maximum uptake

^† IC₅₀ value

^‡ Diastereoisomers

-not applicable/not reported

T:B: tumour-to-blood ratio at corresponding time point; T:M: tumour-to-muscle ratio at corresponding time point; HT-29: human colorectal cancer cell line; U373: human glioblastoma cell line; HCT 116: human colorectal cancer cell line; SK-RC-52: human clear cell renal cell carcinoma cell line