Nourollah Sadeghzadeh, Hadi Pishsaraie, Yaser Ghasemi, Iman Emrarian,
Volume 25, Issue 129 (10-2015)
Abstract
Background and purpose: Bombesin shows very high-affinity for the Gasterin releasing peptide (GRP) receptors which are over expressed in different human tumors such as breast and prostate. The aim of this study was to identify a new bombesin derivative labeled with 99mTc via HYNIC that might be used as a noninvasive tool for diagnosis of GRP receptor expressing tumors.
Materials and methods: Prepared bombein derivatives were radiolabeled with 99mTc at 100 °C for 10 min by exchange method and radiochemical analysis was performed using ITLC and HPLC methods. The stability of radiopeptide was checked in the presence of human serum at 37 °C and saline for up to 24 h.
Results: [99mTc-EDDA/tricin/HYNIC-(Ser)3-D-Phe13]BN(7-14) and [99mTc-EDDA/tricin/ HYNIC-(Gly)3-D-Phe13]BN (7-14) were obtained with radiochemical purities of >95%. Results of in-vitro studies demonstrated a high stability in serum and saline.
Conclusion: Radiolabeling of this novel conjugates with 99mTc were easily performed using exchange labeling. The prepared 99mTc-HYNIC-BN conjugates demonstrated some potential as site-directed diagnostic radiopharmaceuticals. Therefore, more in vivo studies are required.
Mohammad Hasankhah, Iman Emrarian, Nourollah Sadeghzade, Seyed Mohammad Abedi,
Volume 26, Issue 140 (9-2016)
Abstract
Background and purpose: Bombesin is a 14-amino acid peptide with high biological functions which has a high affinity to GRP )Gastrin releasing peptide( receptor. GRP receptors are overexpressed in many malignant tumors such as prostate and breast cancers. The purpose of this study was to prepare [HYNIC-(Gly)3-D-Phe13]Bombesin(7-14) to label it easily by 99mTc and to evaluate it as a potential agent for imaging the tumors that have GRP receptors.
Materials and methods: In this experimental study, the prepared derivative Bombesin was radiolabelled by 99mTc at 100°C in 10 minutes using the exchange method and radiolabelling analysis was applied by TLC and HPLC. Specific absorption test and specific internalization using prostate cancer cells PC-3 was done by blocking and unblocking the receptors. Biodistribution were determined in normal mice.
Results: More than 95% radiolabelling was obtained. Specific absorption and internalization after 4 hours were 17.9% and 9.5%, respectively in PC-3 cancer cells. Biodistribution data showed rapid clearance from blood with major renal excretion and specific binding to tissues that have GRP receptors such as pancreas.
Conclusion: Conjugated peptide radiolabelled with 99mTc has promising characteristics as potential agent for imaging the tumors that overexpress the GRP receptors.
Iman Emrariani, Nourollah Sadeghzadeh, Saeid Abediankenari, Seyed Mohammad Abedi,
Volume 33, Issue 1 (11-2023)
Abstract
Background and purpose: The selection of co-ligand has a profound effect on the labeling efficiency, biodistribution, and tumor-targeting ability of 99mTc-labeled HYNIC-conjugated peptides. This study compared the in-vitro and in-vivo properties from the 99mTc-labeling of 6-Hydrazinonicotinamide-conjugated neurotensin (HYNIC-[βAla7-Tle12] NT (5-13)) by Tricine/EDDA and Tricine as two co-ligand systems.
Materials and methods: After radiolabeling, cellular specific binding, affinity and internalization were evaluated toward the HT-29 cell line, as neurotensin overexpressing cells for both of them. Finally, the biodistribution studies were performed on HT-29 xenografted tumor-bearing nude mice, and the imaging was performed using a gamma camera.
Results: The radiochemical purity of 99mTc labeled peptide with tricine and tricine/EDDA as co-ligands was found over 95%, and they showed desirable saline and serum stability up to 24 h. The dissociation constant (Kd) value for radiolabeled peptide with tricine and tricine/EDDA toward NT receptors were determined as 50.41 ± 9.76 and 32.66 ± 4.00, respectively. Internalization of radiolabeled peptide with tricine/EDDA was reported almost 2-fold more than radiolabeled peptide with tricine as co-ligand for HT-29 cell line after 4 h incubation. In biodistribution and imaging, the tumor/muscle activity ratio was 2.30 and 4.20, 1.74 and 2.28 at 2 h post-injection with tricine and tricine/EDDA, respectively.
Conclusion: Despite relatively similar radiochemical properties of both peptide radio-complexes with 99mTc, the complex labeled with a mixture of tricine/EDDA as co-ligands showed more suitable in vivo properties than tricine.
