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.
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.
Sajjad Molavipordanjani,
Volume 34, Issue 240 (12-2024)
Abstract
Background and purpose: The serotonin receptor (5-HTR) family includes seven distinct members, with the serotonin seven receptor (5-HT7R) being the newest addition to this family. The
5-HT7R contributes to different physiological and pathological processes including glioblastoma multiforme (GBM). The standard treatment for GBM involves a combination of surgery, radiotherapy and chemotherapy. However, GBM tumors are highly diffuse and exhibit a significant risk of recurrence. As a result, the use of advanced monitoring techniques, such as nuclear medicine imaging, is essential. This study aims to develop an effective radiotracer for imaging 5-HT7R overexpression in GBM by utilizing a radiolabeled aryl piperazine derivative (99mTc(CO)3-[5]).
Materials and methods: In this experimental study, compound 5 1-(3-nitropyridin-2-yl) piperazine was designed, synthesized, and characterized, then radiolabeled with fac-[99mTc(CO)3(H2O)3]+ to produce 99mTc(CO)3-[5]. Quality control tests, including high-حperformance liquid chromatography (HPLC) and thin-layer chromatography (TLC) were performed to determine the radiochemical purity. The specific binding study was performed using various cell lines, including U-87 MG, MCF-7, SKBR3, HT-29, and A549. The affinity of 99mTc(CO)3-[5] for 5-HT7R was evaluated using the U87-MG cell line and the maximum binding capacity (Bmax,) and dissociation constant (Kd) were calculated.
Results: The initial radiochemical purity of 99mTc(CO)3-[5] was greater than 95% (RCP>95%). This radiotracer displayed moderate affinity for the U87-MG cell line’s 5-HT7R and lower affinity for MCF-7, SKBR3, HT-29, and A549 cell lines. The calculated Bmax, and Kd of the radioligands were 48±9.23nM and 2.94±0.09×105.
Conclusion: Compound 5 can be quantitatively radiolabeled with fac-[99mTc(CO)3(H2O)3]+ resulting in the radiotracer (99mTc(CO)3-[5]). The initial radiochemical purity of this radiotracer is approximately 95%; however, its stability decreases over time. 99mTc(CO)3-[5] recognizes the 5-HT7R on the surface of U87-MG cells and binds to this receptor with moderate affinity.
