Preparation and Bioevaluation of Novel 99mTc-Labeled Complexes with a 2-Nitroimidazole HYNIC Derivative for Imaging Tumor Hypoxia

Abstract

To develop novel 99mTc-labeled single-photon emission computed tomography (SPECT) radiotracers for imaging hypoxia, a novel HYNICNM ligand (6-hydrazinonicotinamide (HYNIC) 2-nitroimidazole derivative) was designed and synthesized. It was radiolabeled with technetium-99m using tricine/trisodium triphenylphosphine-3,3′,3′′-trisulfonate (TPPTS), tricine/sodium triphenylphosphine-3-monosulfonate (TPPMS) and tricine as co-ligands to obtain [99mTc]Tc-tricine-TPPTS-HYNICNM, [99mTc]Tc-tricine-TPPMS-HYNICNM, and [99mTc]Tc-(tricine)2-HYNICNM, respectively. The three technetium-99m complexes were radiolabeled in one step with a high yield (95%) and had good stability in saline and mouse serum. In vitro cellular uptake results showed that these complexes exhibited good hypoxic selectivity. The partition coefficient indicated that they were good hydrophilic complexes, and [99mTc]Tc-tricine-TPPTS-HYNICNM displayed the highest hydrophilicity (-3.02 ± 0.08). The biodistribution in mice bearing S180 tumors showed that [99mTc]Tc-tricine-TPPTS-HYNICNM exhibited higher tumor uptake (1.05 ± 0.27% IA/g); more rapid clearance from the liver, blood, muscle, and other non-target organs; and a higher tumor/non-target ratio, especially for the tumor/liver ratio (1.95), than [99mTc]Tc-tricine-TPPMS-HYNICNM and [99mTc]Tc-(tricine)2-HYNICNM. The results of single-photon emission computed tomography (SPECT) imaging studies of [99mTc]Tc-tricine-TPPTS-HYNICNM were in accordance with the biodistribution results, which suggested that [99mTc]Tc-tricine-TPPTS-HYNICNM is a promising agent for imaging tumor hypoxia.

A Simple Kit Formulation for Preparation and Exploratory Human Studies of a Novel 99mTc-Labeled Fibroblast Activation Protein Inhibitor Tracer for Imaging of the Fibroblast Activation Protein in Cancers

“…The linker, which connects the targeting group with the chelating group, plays an important role in adjusting the affinity of tracers and their biodistribution properties in organisms. Using amino acids as linkers could improve the hydrophilicity and alter the metabolism of radioactive drugs; thus, this approach may reduce the uptake of the tracer by nontarget organs such as the kidney and improve the uptake of radiotracers in tumors. , Therefore, in this work, hydrophilic d -proline was selected as a linker to connect the hydrazinonicotinamide (HYNIC) group and FAPI moiety, and tricine and 3,3′,3″-phosphanetriyltris trisodium salt (TPPTS) were used as co-ligands to form a technetium complex , to obtain a potential tumor imaging agent targeting FAP.…”

Recent Developments in PET and SPECT Radiotracers as Radiopharmaceuticals for Hypoxia Tumors

“…Scintigraphy imaging studies in mice bearing S180 tumors also showed a h accumulation of [ 99m Tc]46 in tumors with a tumor/normal tissue ratio of 3.39 ± 0.38, wh were in accordance with the biodistribution studies of [ 99m Tc]46. 50) were developed by Zhang and co-workers (Figure 23) [150]. In vitro stud showed that the three 99m Tc-labeled complexes remained stable in saline and in mou serum, and all were hydrophilic.…”

Synthesis and Bioevaluation of Novel Technetium-99m-Labeled Complexes with Norfloxacin HYNIC Derivatives for Bacterial Infection Imaging

“…The synthesis of compound 1 (HYNIC active ester) has been previously reported. 23 Compound 2 (HY-NICNF) was synthesized according to the reported literature, 22 and the reaction route is shown in Scheme 1. The general procedure for the preparation of HYNIC norfloxacin was as follows.…”