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Background: The 5-hydroxytryptamine receptor (5-HTR) family includes seven classes of receptors. The 5-HT 7 R is the newest member of this family and contributes to different physiological and pathological processes. As a pathology, glioblastoma multiform (GBM) overexpresses 5-HT 7 R; hence, this study aims to develop radiolabeled aryl piperazine derivatives as 5-HT 7 R imaging agents.  METHODS: Compounds 6 and 7 as 1-(3-nitropyridin-2-yl)piperazine derivatives were radiolabeled with fac-[ 99m Tc(CO) 3 (H 2 O) 3 ] + and 99m Tc(CO) 3 -[6] and 99m Tc(CO) 3 -[7] were obtained with high radiochemical purity (RCP > 94%). The stability of the radiotracers was evaluated in both saline and mouse serum. Specific binding on different cell lines including U-87 MG, MCF-7, SKBR3, and HT-29 was performed. The biodistribution of these radiotracers was evaluated in normal and U-87 MG Xenografted models. Finally, 99m Tc(CO) 3 -[6] and 99m Tc(CO) 3 -[7] were applied for in vivo imaging in U-87 MG Xenografted models., Results: Specific binding study indicates that 99m Tc(CO) 3 -[6] and 99m Tc(CO) 3 -[7] can recognize 5-HT 7 R of U87-MG cell line. The biodistribution study in normal mice indicates that the brain uptake of 99m Tc(CO) 3 -[6] and 99m Tc(CO) 3 -[7] is the highest at 30 min post-injection (0.8 ± 0.25 and 0.64 ± 0.18%ID/g, respectively). The data of the biodistribution study in the U87-MG xenograft model revealed that these radiotracers could accumulate in the tumor site, and the highest tumor uptake was observed at 60 min post-injection (3.38 ± 0.65 and 3.27 ± 0.5%ID/g, respectively). The injection of pimozide can block the tumor's radiotracer uptake, indicating the binding of these radiotracers to the 5-HT 7 R. The imaging study in the xenograft model also confirms the biodistribution data. The acquired images clearly show the tumor site, and the tumor-to-muscle ratio for 99m Tc(CO) 3 -[6] and 99m Tc(CO) 3 -[7] at 60 min was 3.33 and 3.88, respectively.  CONCLUSIONS: 99m Tc(CO) 3 -[6] and 99m Tc(CO) 3 -[7] can visualize tumor in the U87-MG xenograft model  due to their affinity toward 5-HT 7 R., (© 2023. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Background: Peptide receptor radionuclide therapy (PRRT) has evolved in cancer therapy and diagnosis. LTVSPWY, as a peptide, can target HER2 receptor; on the other hand, 177 Lu emits β - which is helpful for cancer therapy. The radiolabeling of LTVSPWY with 177 Lu results in a therapeutic agent ( 177 Lu-DOTA-LTVSPWY) capable of cancer treatment., Methods: 177 Lu-DOTA-LTVSPWY was prepared with high radiochemical purity (RCP). The stability was investigated in saline and human serum. The radiotracer affinity toward the SKOV-3 cell line with overexpression of the HER2 receptor was evaluated. Then the impact of the radiotracer on the colony formation of the SKOV-3 cell line was investigated with colony assay. Moreover, the biodistribution of this radiotracer in SKOV-3 xenograft tumor-bearing nude mice were also studied to determine the radiotracer accumulation in the tumor site. The mice were treated with 177 Lu-DOTA-LTVSPWY and subjected to histopathological evaluation., Results: The RCP of 177 Lu-DOTA-LTVSPWY after radiolabeling and stability tests was more than 97.7%. The radiotracer displayed high affinity toward the SKOV-3 cell line (K D  = 6.6 ± 3.2 nM). Treatment of the SKOV-3 cell line with the radiotracer reduces the SKOV-3 colony survival to less than 3% for 5 MBq of the radiotracer. Tumor-to-muscle (T/M) ratio is the highest at 48 h and 1 h post-injection (2.3 and 4.75, respectively). The histopathological study also confirms the cellular damage to the tumor tissue., Conclusions: 177 Lu-DOTA-LTVSPWY can recognize HER2 receptors in vivo and in vitro; hence, it can serve as a therapeutic agent., (© 2023. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Objective: Hepatotoxicity remains amongst the restricting factors of Methotrexate (MTX)-associated cancer therapy, especially in high doses of chemo-drugs or prolonged treatment. Due to the known protective effects of Melissa officinalis (M. officinalis), the aqueous extract of this plant was evaluated to ameliorate MTX-associated hepatotoxicity in rats., Methods: Adult female Wistar rats were received or not M. officinalis aqueous extract at doses of 100 mg/kg (for 14 and 24 consecutive days) and 2 g/kg (for 14 consecutive days) by gavage technique. MTX (20 mg/kg) was intraperitoneally injected on the 10th- and 20th-day post-M. officinalis treatment. 24 h after the last day of treatment, 99m Tc-phytate was intravenously injected through the tail of rats. Animals were killed at 20 min after radiocolloid injection, and vital tissues including the liver and spleen were isolated, weighed, and their radioactivity was counted. As well, 99m Tc-phytate scintigraphy and histopathology of the liver were performed for higher accuracy., Result: A significant increase in liver radioactivity was detected in M. officinalis+MTX receiving groups compared with the MTX rats which were more robust at a dose of 100 mg/kg for 14 days. Also, a significant reduction in liver radioactivity was evident with M. officinalis extract at a dose of 2 g/kg for 14 days in comparison with the control group, this reduction was not significant at the lower dose of 100 mg/kg. Gamma scintigraphy and histopathological examinations confirmed the hepatoprotective effect of M. officinalis vs MTX-induced liver injury in rats., Conclusion: In conclusion, we highlighted the liver uptake of 99m Tc-phytate as a valuable method for assessment of liver toxicity and addressed that M. officinalis pretreatment (100 mg/kg for 14 days) ameliorates the MTX-associated hepatotoxicity in rats; however, M. officinalis itself induces liver toxicity at higher doses., (© 2022. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Purpose: In this study, we designed a new linear 6-Hydrazinonicotinamide (HYNIC)-conjugated peptide (HYNIC-KRWrNM) (M-6) and labeled with technetium-99m for gamma imaging of glioblastoma as a α v β 3 -positive tumor. We evaluated tumor targeting ability of this radio-peptide and compared with previous 99m Tc-labeled HYNIC-conjugated RGD analogue peptides., Procedures: One new linear peptide (HYNIC-KRWrNM) (M-6) was designed and labeled with technetium-99m in the presence of 2-[[1,3-dihydroxy-2-(hydroxymethyl) propan-2-yl] amino] acetic acid (Tricine)/Ethylenediamine-N,N'-diacetic acid (EDDA) as co-ligand system. Then, this 99m Tc-labeled peptide ([ 99m Tc]Tc-M-7) was evaluated for in vitro stability in saline and serum, specific binding assay, internalization, and binding affinity (K d ). In addition, we performed biodistribution study and planar imaging on nude mice bearing U87-MG xenograft as a α v β 3 -positive tumor., Results: The radiochemical yield of [ 99m Tc]Tc-M-7 was obtained ˃95%. This 99m Tc-labeled peptide remained stable and intact in saline solution after 24 h incubation. In addition, metabolic stability of this 99m Tc-labeled peptide was obtained ˃60% after 4 h incubation in serum. The K d value for [ 99m Tc]Tc-M-7 was obtained 5.2 ± 1.0 nM. Based on biodistribution results in nude mice bearing U87-MG xenograft, tumor/muscle activity ratio was 6.22 and decreased to 1.89 in blocking group at the same time point (4 h p.i.). The blocking experiment results also indicated that tumor uptake and kidney uptake were α v β 3 -mediated. In comparison with previous HYNIC-conjugated RGD analogue peptides, kidneys had the highest uptake of this 99m Tc-labeled peptide (52.29 ± 11.48 at 1.5 h p.i. and 27.04 ± 0.66%ID/g at 4 h p.i.). Finally, similar to previous 99m Tc-labeled HYNIC-conjugated RGD analogue peptides, [ 99m Tc]Tc-M-7 showed acceptable tumor uptake after 4 h post-injection (based on ROI technique, target-to-background activity ratio = 3.80)., Conclusions: This small linear 99m Tc-labeled peptide, with high affinity to α v β 3 integrin, desirable water solubility, and cost efficient, demonstrates a potent tumor targeting ability as well as previous HYNIC-conjugated RGD analogue peptides. Hence, [ 99m Tc]Tc-M-7 can be of service to as a new candidate for early detection of α v β 3 -positive tumors., (© 2022. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)