Dataset Information

Synthesis, characterization and biological evaluation of Pd(ii), Cu(ii), Re(i) and ^99mTc(i) thiazole-based complexes.

ABSTRACT: A new thiazole-containing multidentate ligand 2-((2-phenylthiazol-4-yl)methylthio)ethanamine, L, was synthesized and used to prepare new complexes of the formula Pd^IILCl₂ (Pd-L), Cu^IIL₂Cl₂ (Cu-L) and fac-[Re/^99mTc^I(CO)₃(L)]⁺ (Re/^99mTc-L). The ligand L and the metal complexes were characterized spectroscopically. Furthermore, the structures of Re-L and Cu-L were elucidated by X-ray crystallography. Ligand L acts as a bidentate (N_th, S) chelator in Pd-L, as a bidentate (N, S) chelator in Cu-L and as a tridentate (N_th, S, N) chelator in Re-L. The radiotracer ^99mTc-L was synthesized in high yield and characterised by HPLC comparison with the Re-L analog. The synthesized compounds were evaluated for their anti-inflammatory and cytotoxic properties. The compounds exhibited low anti-inflammatory activity with Pd-L showing the highest activity among them. The cytotoxic activity of the ligand and the complexes against several human cancer cell lines (cervical adenocarcinoma HeLa, colorectal adenocarcinoma LS-174T, lung adenocarcinoma A549, breast adenocarcinoma MDA-MB-231 and normal human lung fibroblast cell line MRC-5) was examined using the MTT assay. The complex Cu-L exhibited the highest cytotoxicity and the complex Pd-L showed the best tumor selectivity. The changes in the cell cycle phase distribution were determined by flow cytometry and it was found that ligand L shows the highest apoptotic activity. The biodistribution studies of ^99mTc-L in mice showed fast tissue clearance. Of all the thiazole-containing compounds, the palladium complex appears to be more promising for future efforts.

SUBMITTER: Maskovic JM

PROVIDER: S-EPMC6072317 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Synthesis, characterization and biological evaluation of Pd(ii), Cu(ii), Re(i) and 99mTc(i) thiazole-based complexes.

Mašković Jelena M JM Hatzidimitriou Antonios A Damjanović Ana A Stanojković Tatjana P TP Trifunović Srećko R SR Geronikaki Athina A AA Papagiannopoulou Dionysia D

MedChemComm 20180413 5

A new thiazole-containing multidentate ligand 2-((2-phenylthiazol-4-yl)methylthio)ethanamine, L, was synthesized and used to prepare new complexes of the formula PdIILCl2 (Pd-L), CuIIL2Cl2 (Cu-L) and fac-[Re/99mTcI(CO)3(L)]+ (Re/99mTc-L). The ligand L and the metal complexes were characterized spectroscopically. Furthermore, the structures of Re-L and Cu-L were elucidated by X-ray ...[more]

PMID: 30108972

Similar Datasets

Project description:PurposeSentinel lymph node (SLN) biopsy has proven to reliably stage the clinically negative neck in early-stage oral squamous cell carcinoma (OSCC). [99mTc]Tc-tilmanocept may be of benefit in OSCC with complex lymphatic drainage patterns and close spatial relation to SLNs.MethodsA prospective within-patient evaluation study was designed to compare [99mTc]Tc-tilmanocept with [99mTc]Tc-nanocolloid for SLN detection. A total of 20 patients with early-stage OSCC were included, who underwent lymphoscintigraphy with both tracers. Both lymphoscintigraphic images of each patient were evaluated for SLN detection and radiotracer distribution at 2-4 h post-injection.ResultsThe injection site's remaining radioactivity was significantly lower for [99mTc]Tc-tilmanocept (29.9%), compared with [99mTc]Tc-nanocolloid (60.9%; p < 0.001). Radioactive uptake in SLNs was significantly lower for [99mTc]Tc-tilmanocept (1.95%) compared with [99mTc]Tc-nanocolloid (3.16%; p = 0.010). No significant difference was seen in SLN to injection site ratio in radioactivity between [99mTc]Tc-tilmanocept (0.066) and [99mTc]Tc-nanocolloid (0.054; p = 0.232). A median of 3.0 and 2.5 SLNs were identified with [99mTc]Tc-tilmanocept and [99mTc]Tc-nanocolloid, respectively (p = 0.297). Radioactive uptake in higher echelon nodes was not significantly different between [99mTc]Tc-tilmanocept (0.57%) and [99mTc]Tc-nanocolloid (0.86%) (p = 0.052). A median of 2.0 and 2.5 higher echelon nodes was identified with [99mTc]Tc-tilmanocept and [99mTc]Tc-nanocolloid, respectively (p = 0.083).Conclusion[99mTc]Tc-tilmanocept had a higher injection site clearance, but at the same time a lower uptake in the SLN, resulting in an SLN to injection site ratio, which was not significantly different from [99mTc]Tc-nanocolloid. The relatively low-radioactive uptake in SLNs of [99mTc]Tc-tilmanocept may limit intraoperative detection of SLNs, but can be overcome by a higher injection dose.

Project description:Most epithelial tumors recruit fibroblasts and other nonmalignant cells and activate them into cancer-associated fibroblasts. This often leads to overexpression of the membrane serine protease fibroblast-activating protein (FAP). It has already been shown that DOTA-bearing FAP inhibitors (FAPIs) generate high-contrast images with PET/CT scans. Since SPECT is a lower-cost and more widely available alternative to PET, 99mTc-labeled FAPIs represent attractive tracers for imaging applications in a larger number of patients. Furthermore, the chemically homologous nuclide 188Re is available from generators, which allows FAP-targeted endoradiotherapy. Methods: For the preparation of 99mTc-tricarbonyl complexes, a chelator was selected whose carboxylic acids can easily be converted into various derivatives in the finished product, enabling a platform strategy based on the original tracer. The obtained 99mTc complexes were investigated in vitro by binding and competition experiments on FAP-transfected HT-1080 (HT-1080-FAP) or on mouse FAP-expressing (HEK-muFAP) and CD26-expressing (HEKCD26) HEK cells and characterized by planar scintigraphy and organ distribution studies in tumor-bearing mice. Furthermore, a first-in-humans application was done on 2 patients with ovarian and pancreatic cancer, respectively. Results: 99mTc-FAPI-19 showed specific binding to recombinant FAP-expressing cells with high affinity. Unfortunately, liver accumulation, biliary excretion, and no tumor uptake were observed on planar scintigraphy for a HT-1080-FAP-xenotransplanted mouse. To improve the pharmacokinetic properties, hydrophilic amino acids were attached to the chelator moiety of the compound. The resulting 99mTc-labeled FAPI tracers revealed excellent binding properties (≤45% binding; >95% internalization), high affinity (half-maximal inhibitory concentration, 6.4-12.7 nM), and significant tumor uptake (≤5.4% injected dose per gram of tissue) in biodistribution studies. The lead candidate 99mTc-FAPI-34 was applied for diagnostic scintigraphy and SPECT of patients with metastasized ovarian and pancreatic cancer for follow-up to therapy with 90Y-FAPI-46. 99mTc-FAPI-34 accumulated in the tumor lesions, as also shown on PET/CT imaging using 68Ga-FAPI-46. Conclusion: 99mTc-FAPI-34 represents a powerful tracer for diagnostic scintigraphy, especially when PET imaging is not available. Additionally, the chelator used in this compound allows labeling with the therapeutic nuclide 188Re, which is planned for the near future.

Dataset Information

Synthesis, characterization and biological evaluation of Pd(ii), Cu(ii), Re(i) and ^99mTc(i) thiazole-based complexes.

Publications

Synthesis, characterization and biological evaluation of Pd(ii), Cu(ii), Re(i) and <sup>99m</sup>Tc(i) thiazole-based complexes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets