Design, synthesis and evaluation of ¹⁸F-labeled cationic carbonic anhydrase IX inhibitors for PET imaging

Figures & data

Figure 1. Reported sulfonamide derivatives that are CA-IX selective agents. (A) Trimeric AmBF₃-(AEBS)₃ and AmBF₃-(ABS)₃, (B) Ga-DOTA-AEBSA, and (C) cationic sulfonamide derivatives.

Figure 2. Chemical structures of three cationic carbonic anhydrase IX inhibitors evaluated in this study.

Scheme 1. Synthesis of cationic carbonic anhydrase IX inhibitors 1–3.

Table 1. Inhibition constants (K_i) of cationic inhibitors 1–3 to carbonic anhydrases I, II, IV, and IX as determined by a stopped-flow CO₂ hydration assay. Errors in the range of 5–10% of the reported value from three different assays.

	Inhibition constant (Ki, μM)
Compound	CA-I	CA-II	CA-IV	CA-IX
1	0.89	0.72	>50.0	0.44
2	0.52	0.07	9.54	0.22
3	0.78	0.48	3.63	0.96
Acetazolamide	0.25	0.01	0.08	0.03

Scheme 2. (A) Synthesis of the radiolabeling precursor 8. (B) Synthesis of ¹⁸F-labeled 2.

Figure 3. HPLC chromatograms of ¹⁸F-labeled 2 from (A) QC sample, or plasma sample after being incubated at 37 °C for (B) 5 min, (C) 15 min, or (D) 60 min.

Figure 4. Biodistribution of ¹⁸F-labeled 2 at 1 h post-injection in HT-29 tumor-bearing mice. Values (%ID/g) are presented as mean ± standard deviation (n = 5).

Figure 5. Representative PET and CT images acquired at 1 h post-injection with ¹⁸F-labeled 2 in HT-29 colorectal cancer xenograft-bearing mice. Arrow indicates location of tumor.

Figure 6. Time activity curves for ¹⁸F-labeled 2 using ROIs drawn around high activity organs (A) heart, liver, and kidneys, and low activity organs (B) tumor, bone, muscle, and muscle.