Search Results
Abstract
[99mTc-EDDA-HYNIC-D-Phe1, Tyr3]-Ocreotide (99mTc-EDDA-HYNIC-TOC) increasingly emerges to be an alternative tool for somatostatin receptor (SSTR) scintigraphy of neuroendocrine tumours. The high quality of this radiopharmaceutical and its uniformity are very important facts for application of this preparation in clinical practice. Various factors may influence the radiochemical purity (RCP) of certain reagent kits. Some of these include the amount of activity added to the reagent kit, heating time and the age of the formulated kit. The effect of these factors on RCP of 99mTc-EDDA-HYNIC-TOC has been investigated using high performance liquid chromatography (HPLC) and instant thin layer chromatography (ITLC).
Abstract
A conjugate of 6-hydrazinopyridine-3-carboxylic acid (HYNIC) with the amino analogue of metronidazole (MN) was synthesized through a multiple-step reaction. HYNIC-MN could be labeled easily and efficiently with 99mTc using N-(2-hydroxy-1,1-bis(hydroxymethyl)ethyl)glycine (tricine) and ethylenediamine -N,N′-diacetic acid (EDDA) as coligands to form the 99mTc–HYNIC–MN complex in high yield (>95%). Its partition coefficient indicated that it was a good hydrophilic complex. The tumor cell experiment showed that the 99mTc–HYNIC–MN complex had a certain hypoxic selectivity. The biodistribution studies of 99mTc–HYNIC–MN in Kunming mice bearing S180 tumor showed a favorable tissue distribution profile with high tumor uptake, and low or negligible accumulation in non-target organs, suggesting 99mTc–HYNIC–MN would be a novel potential tumor hypoxia imaging agent.
Abstract
A conjugate of 6-hydrazinopyridine-3-carboxylic acid (HYNIC) with aminomethylenediphosphonic acid (AMDP) was synthesized through a multiple-step reaction. HYNIC–AMDP could be labeled easily and efficiently with 99mTc using N-(2-hydroxy-1,1-bis(hydroxymethyl)ethyl)glycine (tricine) as coligand to form the 99mTc–HYNIC–AMDP complex in high yield (> 95%). Its partition coefficient indicated that it was a good hydrophilic complex. The biodistribution studies of 99mTc–HYNIC–AMDP in normal ICR mice showed that this complex had high bone uptake and low or negligible accumulation in non-target organs. As compared with 99mTc–MDP, 99mTc–HYNIC–AMDP had a higher bone uptake and the ratios of bone/blood and bone/muscle at early time after injection, suggesting that it could be potentially useful for bone imaging at an earlier time after injection according to further investigations of the biological behavior of this complex.
Abstract
In vivo imaging of tumours using radiolabelled somatostatin (SST) analogues has become an accepted clinical tool in oncology. HYNIC-Tyr3 octreotide and Tyr3 octreotide were synthesized by FMOC solid-phase peptide synthesis using a semi-automated synthesizer. These were analyzed and purified by RP-HPLC, mass spectroscopy, IR spectroscopy, 1H NMR and 13C NMR. The prochelator 6-BOC-HYNIC was also synthesised and characterised indigenously. HYNIC-Tyr3 octreotide was labelled with 99mTc using Tricine and EDDA as coligand by SnCl2 method. Labelling with 99mTc was performed at 100 °C for 15 min and radiochemical analysis by ITLC and HPLC methods. The radiochemical purity of the complex was over 98% and log p value was found to be −1.27 ± 0.12. The stability of radiolabelled peptide complex was checked at 37 °C up to 24 h. Blood clearance and protein-binding study was also performed. In vivo biodistribution studies in rat showed uptake of 99mTc-HYNIC-TOC in kidney than any other organs. The blood clearance was faster with rapid excretion through kidneys and relatively low uptake in liver.
Abstract
A variety of human tumors like prostate and breast cancer express bombesin receptors. Due to this a new bombesin analogue was labeled with 99mTc via HYNIC and tricine as a coligand and investigated further. Peptide was synthesized on a solid phase using Fmoc strategy. Labeling with 99mTc was performed at 100 °C for 10 min and radiochemical analysis involved ITLC and HPLC methods. The stability of radiopeptide was checked in the presence of human serum at 37 °C up to 24 h. Internalization was studied with the human GRP receptor cell line PC-3. The biodistribution was studied in mice. Labeling yield of >98% was obtained corresponding to a specific activity of ~80.9 GBq/μmol. Radiopeptide internalization into PC-3 cells was moderate and specific (10.7 ± 1.2% at 4 h). A high and specific GRP receptor expressing mouse tumor and pancreas uptake (1.12 ± 0.08 and 1.04 ± 0.11% ID/g after 1 h respectively) was also determined.
Abstract
Tumors such as prostate, small cell lung cancer, breast, gastric and colon cancer are known to overexpress receptors to bombesin (BBN). In this study, a new bombesin analogue was labeled with 99mTc via HYNIC and tricine/EDDA as coligands and investigated further. HYNIC-GABA-Bombesin (7–14) NH2 was synthesized using a standard Fmoc strategy. Labeling with 99mTc was performed at 100 °C for 10 min and radiochemical analysis involved ITLC and HPLC methods. The stability of radiopeptide was checked in the presence of humane serum at 37 °C up to 24 h. The receptor bound internalization and externalization rates were studied in GRP receptor expressing PC-3 cells. Biodistribution of radiopeptide was studied in nude mice bearing PC-3 tumor. Labeling yield of >98% was obtained corresponding to a specific activity of ~2.6 MBq/nmol. Peptide conjugate showed good stability in the presence of human serum. The radioligand showed high and specific internalization into PC-3 cells (14.63 ± 0.41% at 4 h). In biodistribution studies, a receptor-specific uptake was observed in GRP-receptor-positive organs so that after 4 h the uptakes in mouse tumor and pancreas were 1.31 ± 0.18 and 1.2 ± 0.13% ID/g, respectively.
Abstract
Bombesin (BNN)-like peptides have very high binding affinity for the gastrin-releasing peptide (GRP) receptor. The goal of the current study was to optimize the labeling conditions of a new 99mTc-radiolabeled BNN-like peptide based on the bifunctional chelating ligand HYNIC using different co-ligands (EDDA and tricine). The radiolabeling conditions (pH, amount of co-ligand, amount of stannous chloride, temperature and reaction time) for newly-formed 99mTc-tricine-HYNIC-Q-Litorin and 99mTc-EDDA-HYNIC-Q-Litorin were optimized and evaluated by RHPLC and RTLC. Radiochemical yields for 99mTc-tricine-HYNIC-Q-Litorin and 99mTc-EDDA-HYNIC-Q-Litorin were 98.0 ± 1.7 and 97.5 ± 2.5%, respectively. When EDDA was used as co-ligand, the labeling of 99mTc-EDDA-HYNIC-Q-Litorin was optimal in the following reaction mixture: HYNIC-peptide: EDDA: 10 μg/5 mg, pH 3, SnCl2 concentration: 12 μg/0.1 mL, reaction temperature: 100 °C, reaction time: 15 min. Besides, the optimum conditions were HYNIC-peptide:tricine: 10 μg/50 mg, pH 5, SnCl2 concentration: 12 μg/0.1 mL, reaction temperature: 100 °C, reaction time: 15 min for preparing 99mTc-tricine-HYNIC-Q-Litorin. The manufactured 99mTc-HYNIC-Q-Litorin conjugates may offer new possibilities for imaging cancer cells expressing bombesin receptors.
Abstract
The present study shows the development of 99mTc-labeling of the P149-QY peptide, a modified fragment of human alpha-fetoprotein (hAFP), with the intention of potential application for diagnosis of AFP positive tumors. An efficient preparation of 99mTc-labeled P149-QY using HYNIC was developed. It has been shown that the free sulfhydryl groups in P149-QY can be protected with N-ethylmaleimide, preventing the radiolabeled peptide from loss of its biological activity. The biodistribution studies revealed favorable pharmacokinetics and a better specificity to the mammary adenocarcinoma tumor for the SH-protected radiolabeled P149-QY peptide in comparison to the radioiodinated and to the directly 99mTc-labeled peptide.
