Preclinical evaluation of [99mTc/EDDA/tricine/HYNIC0, 1-Nal3, Thr8]-octreotide as a new analogue in the detection of somatostatin-receptor-positive tumors

Ghanei, Mostafa; Najafi, Rezvan; Shafiei, Mohammad; Mazidi, Mohammad; Ebrahimi, S E Sadat

doi:10.1016/j.nucmedbio.2007.06.006

Cited by 28 publications

(22 citation statements)

References 15 publications

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“…Two new octreotide analogs DOMA-Asn 3 -Octreotate (DOMA-AATE), DOMA-Pro 3 -Octreotate (DOMA-PATE), and HYNIC-Tyr 3 -octreotide (HYNIC-TOC) were synthesized by standard Fmoc solid-phase synthesis (SPPS) (Kwekkeboom and Krenning 2002;Panwar et al2005;Gandomkar et al 2007) on acid sensitive H-Thr(tBu)-(2-chlorotrityl) resin for DOMA-AATE, DOMA-PATE and O-t-butylthreoninol-(2-chlorotrityl) resin for HYNIC-TOC. The amino acid sequence of the peptides Asn 3 -octreotate was D-Phe-Cys-Asn-(D)Trp-Lys-Thr-Cys-Thr-OH, Pro 3 -octreotate was D-Phe-Cys-Pro-Trp-Lys-Thr-Cys-Thr-OH and for Tyr 3 -octreotide was D-Phe-Cys-Tyr-(D)Trp-LysThr-Cys-Thr-OH.…”

Section: Solid-phase Peptide Synthesismentioning

confidence: 99%

“…The binding affinity of DOMA-AATE/DOMA-PATE was performed in a competition binding assay (Nikolopoulou et al 2006;Maina et al 2006;Gandomkar et al 2007;De et al 2012) against 99m Tc-HYNIC-TOC as the radioligand.…”

Section: Receptor-binding Studymentioning

confidence: 99%

“…Here C6 glioma cell membranes and rat brain cortex membrane homogenates were used as a source of SSTR2. Both the membrane preparations were performed according to a published method (Gandomkar et al 2007;De et al 2012) and the protein concentration of the membrane samples was determined by Bradford reagent (Biorad) using bovine serum albumin as the standard. Typically, 50,000 cpm of radioligand was added in each test tube, containing rat brain cortex (corresponding to 50 μg protein) or C6 cell membrane homogenates (corresponding to 10 μg protein) in the presence of increasing amounts of DOMA-AATE/ DOMA-PATE peptide in a total volume of 300 µL of 50 mM HEPES (pH 7.6, 0.3 % BSA, 5 mM MgCl 2 , 10 µM bacitracin).…”

Section: Receptor-binding Studymentioning

confidence: 99%

“…Internalization experiments were performed using C6 cells seeded at a density of 8-9 × 10 5 cells per well in six-well plates and grown to confluence for 48 h. On the day of the experiment, cells were washed twice with ice-cold internalization medium prepared with DMEM nutrient mixture supplemented by 1 % (v/v) FBS (Nikolopoulou et al 2006;Maina et al 2006;Gandomkar et al 2007;De et al 2012). Furthermore, 1 mL of internalization buffer was added to each well and the plates were incubated at 37 °C for about 1 h. Afterward, approximately 300,000 cpm 99m Tc-DOMA-AATE/ 99m Tc-DOMA-PATE/ 99m Tc-HYNIC-TOC (150 μL, 2.5 pmol per well) were added to the medium and the cells were incubated at 37 °C in triplicates for each time point of 2, 5, 15, 30, 60 and 120 min incubation.…”

Section: Radioligand Internalization Studymentioning

confidence: 99%

“…Solid-phase peptide synthesis (SPSS) has been accepted as a prevailing tool in the generation of several biological important and chemically modified peptides (Arnold et al 2000;Liu and Edwards 1999;Susini and enzymatic degradation (t 1/2 = 2.3 min in blood) and is, therefore, unsuitable for in vivo applications. For this purpose, long-lived small synthetic somatostatin analogs have been developed, such as octreotide, octreotate and their derivatives (Nikolopoulou et al 2006;Gandomkar et al 2007). Numerous studies have focused on improving the target tissue uptake of radiolabeled somatostatin analogs.…”

Section: Introductionmentioning

confidence: 99%

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Radiolabeled new somatostatin analogs conjugated to DOMA chelator used as targeted tumor imaging agent: synthesis and radiobiological evaluation

2015

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Several receptor-specific radiopeptides have been developed and effective in the diagnosis of malignant diseases. Among them, somatostatin receptor (SSTR) scintigraphy with (111)In-DTPA-octreotide has become a tumor diagnostic radiopharmaceutical in nuclear medicine. However, it suffers some drawbacks concerning the imaging properties and elevated radiation burden of (111)In. Here, we report the synthesis of radiolabeled two new octapeptides with improved uptake in SSTR2-positive tumors in comparison with (99m)Tc-HYNIC-Tyr(3)-octreotide (HYNIC-TOC). Octapeptides were synthesized in high yield by Fmoc solid-phase synthesis and coupling the macrocyclic chelator DOMA(1,4,7-Tri-Boc-10-(carboxymethyl)-1,4,7,10-tetraazocyclododecane-1-yl-monoacetic acid) to these peptides for (99m)Tc labeling. New peptides DOMA-Asn(3)-octreotate(DOMA-AATE) and DOMA-Pro(3)-octreotate(DOMA-PATE) were purified, characterized by RP-HPLC, MALDI-mass, (1)H-NMR, (13)C-NMR. Labeling was performed by SnCl2 method to get products with excellent radiochemical purity (97 %). Radiopeptides were found to be substantially stable under physiological condition for 24 h. Internalization and receptor-binding studies were determined in somatostatin receptor-expressing C6-glioma cell line and rat brain cortex membrane and the results compared with HYNIC-TOC as standard. The IC50 values of (99m)Tc-DOMA-AATE(1.10 ± 0.48 nM) and (99m)Tc-DOMA-PATE(1.76 ± 0.06 nM) showed high affinity binding for SSTR2 receptor and they internalized rapidly in C6 cells. Biodistribution and imaging studies were performed in C6 tumor-bearing rat under gamma camera showing significant uptake in kidney, urine and C6 tumor. Radiopeptides exhibited fast blood clearance and rapid elimination through the urinary systems. However, (99m)Tc-DOMA-AATE exhibited the highest tumor to muscle and tumor to blood uptake ratios among three. These favorable characteristics validate (99m)Tc-DOMA-AATE as a more promising (99m)Tc-radiotracer than (99m)Tc-DOMA-PATE, (99m)Tc-HYNIC-TOC for SSTR2-positive tumor scintigraphy.

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Section: Solid-phase Peptide Synthesismentioning

confidence: 99%

Section: Receptor-binding Studymentioning

confidence: 99%

Section: Receptor-binding Studymentioning

confidence: 99%

Section: Radioligand Internalization Studymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Radiolabeled new somatostatin analogs conjugated to DOMA chelator used as targeted tumor imaging agent: synthesis and radiobiological evaluation

2015

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A^99mTc-tricine-HYNIC-labeled peptide targeting the neurotensin receptor for single-photon imaging in malignant tumors

Erfani

Ahrabi

Shafiei

et al. 2014

J. Label Compd. Radiopharm

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In this study, a new neurotensin (NT) analog was labeled with (99m) Tc via HYNIC chelator and tricine as coligand and investigated further. An NT (7-13) analog was prepared, and labeling with (99m) Tc was performed. The internalization rate and biodistribution of radiopeptide were studied in HT-29 cells and nude mice bearing tumor, respectively. Radiolabeling with (99m) Tc was performed at high specific activities (54 MBq/nmol) with an acceptable labeling yield (>95%). In vitro cell line studies showed a specific internalization uptake up to 13.23 ± 0.45% during 4 h which was blocked in the presence of excess cold peptide to 0.83 ± 0.15%. In biodistribution studies, uptake was observed in NT receptor-positive organs so that after 1 h the uptakes in mouse intestine and tumor were 1.23 ± 0.16% ID/g and 1.12 ± 0.11% ID/g, respectively. In animals co-injected with excess cold peptide, reduction uptake in tumor and intestines were 73% (1.10% vs. 0.29% ID/g at 4 h) and 61% (1.22% vs. 0.47% ID/g at 4 h) respectively. Predominant renal excretion pathway with a highest accumulation of activity in bladder was observed for this radiopeptide. This radiolabeled peptide could be a candidate for detection of NT positive tumors.

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Synthesis and evaluation of a ^99mTc‐labeled tubulin‐binding agent for tumor imaging

Erfani

Shamsaei

Mohammadbaghery

et al. 2014

Labelled Comp Radiopharmac

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Cholchicine and its derivatives are very potent tubulin-binding compounds and can be used as a potential tumor targeting agents. In this study, colchicine was labeled with (99m) Tc via hydrazinonicotinic acid (HYNIC) and was investigated further. HYNIC/cholchicine was synthesized and labeling with (99m)Tc was performed at 95 °C for 15 min and radiochemical analysis included HPLC method. The stability of radiconjugate was checked in the presence of human serum at 37 °C up to 24 h. Biodistribution was studied in breast tumor-bearing mice. Labeling yield of 95.8 ± 0.54% was obtained corresponding to a specific activity of 54 MBq/µmol. Radioconjugate showed good stability in the presence of human serum. Biodistribution studies in tumor-bearing mice showed that (99m) Tc/HYNIC/colchicine conjugate accumulated in tumor with good uptake (3.17 ± 0.14% g/g at 1 h post-injection). The radioconjugate was cleared fast from normal organs and showed clearance through urinary and hepatobiliary systems with accumulation of activity in kidneys and intestine. This radioconjugate may be useful to assess the presence of tumor by imaging.

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Preclinical evaluation of [99mTc/EDDA/tricine/HYNIC0, 1-Nal3, Thr8]-octreotide as a new analogue in the detection of somatostatin-receptor-positive tumors

Cited by 28 publications

References 15 publications

Radiolabeled new somatostatin analogs conjugated to DOMA chelator used as targeted tumor imaging agent: synthesis and radiobiological evaluation

Radiolabeled new somatostatin analogs conjugated to DOMA chelator used as targeted tumor imaging agent: synthesis and radiobiological evaluation

A^99mTc-tricine-HYNIC-labeled peptide targeting the neurotensin receptor for single-photon imaging in malignant tumors

Synthesis and evaluation of a ^99mTc‐labeled tubulin‐binding agent for tumor imaging

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Preclinical evaluation of [99mTc/EDDA/tricine/HYNIC0, 1-Nal3, Thr8]-octreotide as a new analogue in the detection of somatostatin-receptor-positive tumors

Cited by 28 publications

References 15 publications

Radiolabeled new somatostatin analogs conjugated to DOMA chelator used as targeted tumor imaging agent: synthesis and radiobiological evaluation

Radiolabeled new somatostatin analogs conjugated to DOMA chelator used as targeted tumor imaging agent: synthesis and radiobiological evaluation

A99mTc-tricine-HYNIC-labeled peptide targeting the neurotensin receptor for single-photon imaging in malignant tumors

Synthesis and evaluation of a 99mTc‐labeled tubulin‐binding agent for tumor imaging

Contact Info

Product

Resources

About

A^99mTc-tricine-HYNIC-labeled peptide targeting the neurotensin receptor for single-photon imaging in malignant tumors

Synthesis and evaluation of a ^99mTc‐labeled tubulin‐binding agent for tumor imaging