Table 6.

PSMA-i labeled with [^99mTc][Tc-HYNIC]²⁺-core.

	HYNIC-PSMA-i Scaffold	Affinity	Performance Clinical Translation	Ref.
[Tc-HYNIC]1 (2013)		a 1.74	Complexes were evaluated on PC3-PIP/PC3-flu xenografts. Whole-body SPECT-CT imaging show low PSMA-dependent tumor uptake and high background activity. Clinical translation: No	[106]
[Tc-HYNIC]2 (2017)		n.d	Complex was evaluated on LNCaP/PC3 xenografts. High and stable PSMA-dependent tumor uptake (9.84 ± 2.63%I D/g at 3 h p.i.). High kidney uptake followed by slow washout (12.63 ± 0.56%ID/g at 3 h p.i.). Low nontarget organs uptake (<2% ID/g at 1 h p.i.). High target-to-nontarget ratios: Tumor-to-blood 271 and tumor-to-muscle 246 at 3 h p.i. Clinical translation: Yes, phase 1	[117]
[Tc-HYNIC]3 (2017)		n.d	Complex was evaluated on LNCaP/PC3 xenografts. High and stable PSMA-dependent tumor uptake (19.45 ± 2.14% ID/g at 2 h p.i). High kidney uptake followed by slow washout. Low nontarget organs uptake (<3% ID/g at 1 h p.i.) High target-to-non-target ratios: Tumor-to-blood 24.33 at 23 h p.i. Clinical translation: Yes, phase 1	[109]
[Tc-HYNIC]4-6 (2020)		b 13.58 23.63 42.36	Complexes were evaluated on LNCaP/PC3 xenografts. PSMA-dependent tumor uptake (3.62 ± 0.78–1.8 ± 0.32% ID/g at 2 h p.i.). High kidney uptake. Low nontarget organs uptake. Clinical translation: No	[110]
[Tc-HYNIC]7 (2020)		c 80 (7)	Complex was evaluated in healthy BALB/C mice. No data on LNCaP/PC3 xenografts were reported. Reduced kidney uptake (37.5 ± 9.5) at 4 h p.i. with respect to other 99mTc-PSMA. Low nontarget organs uptake (<1%ID/g at 4 h p.i). Clinical translation: Yes, phase 1	[111]

^a PSMA inhibitory affinity was determined using the ligand, data are reported as K_i (nM); ^b PSMA inhibitory affinity was determined by using the corresponding technetium-99m complexes. Data are reported as K_D (nM). ^c PSMA inhibitory affinity was determined by using the ligand precursor in competition studies, data are reported as IC₅₀ (nM).