Development of a ⁶⁸Ga‐labelled PET tracer for carbonic anhydrase IX‐overexpressed tumors using the artificial sweetener saccharin

Abstract

In this study, we developed a saccharin (SAC)‐based radiopharmaceutical ( 68 Ga‐NOTA‐SAC) and evaluated the possibility of its application as a PET tracer in the diagnosis of carbonic anhydrase IX (CA IX)‐overexpressed tumors. We did a water‐soluble tetrazolium assay and flow cytometry analysis to identify the cell viability decrease by SAC. The radiochemical purity and stability of 68 Ga‐ NOTA‐SAC in human and mouse serum was greater than 98%. The small animal PET image‐based radioactivity distribution of all organs decreased over time. 68 Ga‐NOTA‐SAC presented the highest tumor‐to‐muscle ratio at 90 min post injection (p.i). The growth rates of tumor‐to‐muscle ratios of 68 Ga‐NOTA‐SAC were 88% at 60 min and 220% at 90 min, compared to 30 min p.i. The potential of 68 Ga‐NOTA‐SAC as a PET tracer is expected to contribute to the diagnostic research on CA IX‐overexpressed tumors with the advantages of a relatively simple synthesis method.

Development and Assessment of 1,5–Diarylpyrazole/Oxime Hybrids Targeting EGFR and JNK–2 as Antiproliferative Agents: A Comprehensive Study through Synthesis, Molecular Docking, and Evaluation

“…Compounds 7a – j , 8a – j , 9a – c , and 10a – c were evaluated for in vitro anticancer activities against five different cancer cell lines, namely, human colorectal adenocarcinoma cell lines DLD-1, human cervical cancer cell line Hela, human pancreatic cancer cell line SUIT-2, human myelogenous leukemia cell line K562, and human hepatocellular carcinoma cell line HepG2 using WST-8 assay at concentrations of 100 µM to investigate the growth inhibition percent (GI%) of each compound using daunorubicin as a reference drug [ 47 ]. From the screening results in Table 1 , compounds 7a – j and 9a – c , which are 1,5-diarylpyrazole acetophenone derivatives, displayed considerable cytotoxicity towards the pancreatic cell line SUIT-2 with GI% ranging from 68 to 104% for compounds 7a – j and 42 to 60% for compounds 9a – c .…”

New Developments in Carbonic Anhydrase IX-Targeted Fluorescence and Nuclear Imaging Agents

“…However, the tumor uptake of 16 was significantly lower than that of 12 ( Figure 7 ) [ 45 ]. Very recently, Shin et al performed the synthesis and evaluation of [ 68 Ga]Ga-NOTA-SAC ( 17 ) for CAIX-overexpressing U87MG tumor detection [ 49 ]. The 68 Ga tracer remained in the U87MG tumor for at least 90 min with 1.2~1.5% ID/g.…”

Design, synthesis, molecular docking and biological evaluation of novel 1,5-diarylpyrazole-N,O-dimethyl hydroxamate derivatives as antiproliferative agents.

“…The newly synthesized compounds were evaluated for in vitro anticancer activity against different five cancer cell lines namely, human colorectal adenocarcinoma cell lines DLD1, human cervical cancer cell line Hela, human pancreatic cancer cell line Suit-2, human myelogenous leukemia cell line K562 and human hepatocellular carcinoma cell line HepG2 using WST-8 assay [23]. All compounds are screened on the five-cell line at concentration 100 µM to investigate the growth inhibition percent (GI%) induced by each compound using Daunorubicin as reference drug.…”