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The technetium-99m ethylene dicysteine (Tc-99m EC) is a radiopharmaceutical used for renal scintigraphy, a noninvasive imaging technique that assesses kidney function as well as urinary tract obstruction. We describe the extrarenal Tc-99m EC uptake in a 70-year-old man with recurrent well-differentiated abdominal liposarcoma. In the present case, both liposarcoma lesions which were diagnosed by abdominal CT scan showed heterogeneous accumulation of the Tc-99m EC.

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ABSTRACT: The fibroblast activation protein (FAP) is a biomarker that is selectively overexpressed on cancer-associated fibroblasts (CAFs) in various types of tumoral tissues and some nonmalignant diseases, including fibrosis, arthritis, cardiovascular, and metabolic diseases. FAP plays a critical role in tumor microenvironment through facilitating proliferation, invasion, angiogenesis, immunosuppression, and drug resistance. Recent studies reveal that FAP might be regarded as a promising target for cancer diagnosis and treatment. FAP-targeted imaging modalities, especially PET, have shown high sensitivity and specificity in detecting FAP-expressing tumors. FAP-targeted imaging can potentially enhance tumor detection, staging, and monitoring of treatment response, and facilitate the development of personalized treatment strategies. This study provides a comprehensive view of FAP and its function in the pathophysiology of cancer and nonmalignant diseases. It also will discuss the characteristics of radiolabeled FAP inhibitors, particularly those based on small molecules, their recent clinical implications in imaging and therapy, and the associated clinical challenges with them. In addition, we present the results of imaging and biodistribution radiotracer 68Ga-FAPI-46 in patients with nonmalignant diseases, including interstitial lung disease, primary biliary cirrhosis, and myocardial infarction, who were referred to our department. Our results show that cardiac FAP-targeted imaging can provide a novel potential biomarker for managing left ventricle remodeling. Moreover, this study has been organized and presented in a manner that offers a comprehensive overview of the current status and prospects of FAPI inhibitors in the diagnosis and treatment of diseases.

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INTRODUCTION: C-X-C Chemokine receptor type 4 (CXCR4) is often overexpressed or overactivated in different types and stages of cancer disease. Therefore, it is considered a promising target for imaging and early detection of primary tumors and metastasis. In the present research, a new cyclo-peptide radiolabelled with 99mTc, 99mTc-Cyclo [D-Phe-D-Tyr-Lys (HYNIC)- D-Arg-2-Nal-Gly-Lys(iPr)], was designed based on the parental LY251029 peptide, as a potential in vivo imaging agent of CXCR4-expressing tumors. METHODS: The radioligand was successfully prepared using the method of Fmoc solid-phase peptide synthesis and was evaluated in biological assessment. Molecular docking findings revealed high affinity (binding energy of -9.7 kcal/mol) and effective interaction of Cyclo [D-Phe- D-Tyr-Lys (HYNIC)-D-Arg-2-Nal-Gly-Lys(iPr)] in the binding pocket of CXCR4 receptor (PDB code: 3OE0) as well. RESULT: The synthesized peptide and its purity were assessed by both reversed-phase high-performance liquid chromatography (RP-HPLC) and mass spectroscopy. High stability (95%, n = 3) in human serum and favorable affinity (Kd = 28.70 ± 13.56 nM and Bmax = 1.896 ± 0.123 fmol/mg protein) in the B16-F10 cell line resulted. Biodistribution evaluation findings and planar image interpretation of mice both showed high affinity and selectivity of the radiotracer to the CXCR4 receptors. CONCLUSION: Therefore, the findings indicate this designed radioligand could be used as a potential SPECT imaging agent in highly proliferated CXCR4 receptor tumors.

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OBJECTIVES: Alzheimer's disease (AD) is a constant, developing brain impairment that is described as the aggregation of misfolded amyloid-beta-peptide (Ab) and abnormal tau protein in the brain. Stem cell therapy became a favorable candidate for the regeneration of neurodegenerative disorders like AD, but there is still shortage of knowledge about the underlying mechanisms. The goal of this survey was the determination of the necroptotic pathway as the possible mechanism for the effect of human adipose-derived stem cells (hADSCs) in the rat model of AD. MATERIALS AND METHODS: Twelve rats were consumed, dividing into four groups: Control, sham, AD model and AD + stem cell groups. We utilized Nissl and Thioflavin S staining for determining histological changes and immunofluorescent techniques for evaluating necroptotic markers in different regions of the hippocampus. RESULTS: The confirmation of AD model was approved with histological examination. The findings indicated more distinct Thio-S stain and an increased number of dead cells in AD rats comparing to other groups. Alternatively, the dead cells number in the CA3 area significantly lessened in AD + stem cell group comparing to AD group. Data showed that hADSCs significantly decreased the expression of necroptotic markers (receptor-interacting protein 1, receptor-interacting protein 3 and mixed lineage kinase domain-like pseudokinase (MLKL)) in AD + stem cell group compared to AD group in different regions of the hippocampus. CONCLUSION: Our findings revealed that the intravenous injection of hADSCs reduced necroptosis and consequently declined the death of neuronal cells in the hippocampus of AD rats.

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In spite of previous efforts, there is lack of a radiotracer for imaging the 5HT1A receptor density in human brain, which is involved in several neurological brain disorders. The aim of this study was to prepare a new derivative of 1-(2-methoxyphenyl)piperazine (MPP) as a main chemical structure of 5HT1A receptor antagonist with 3-carbon linker and radiolabeled by [99m Tc][Tc(CO)3 (H2 O)3 ]+ precursor. Docking studies before chemical synthesis showed similar fashion of interaction for both WAY100635 (potent 5HT1A receptor antagonist) and new designed ligand, despite of addition of 99m Tc(CO)3 group in the structure of new ligand. MPP-(CH2 )3 -N3 was synthesized via three efficient and reliable chemical synthesis steps (more than 80% yield) then radiolabeled by addition of 2-ethynylpyridine and [99m Tc][Tc(CO)3 (H2 O)3 ]+ precursor in one pot procedure (more than 95% radiochemical efficiency) through click chemistry method. After incubation, radiotracer was found stable in vitro up to 2 hours. Binding assays showed about 33% specific binding of radiotracer to the 5HT1A receptors. Brain biodistribution studies indicated (0.26 ± 0.05)% ID/g hippocampus uptake at 30 minutes post injection, which its specificity was verified through blocking studies. These results suggested that new designed radioligand might serve as a potent SPECT imaging agent to estimate status of 5HT1A receptors.

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Aptamers are short single-stranded DNA or RNA oligonucleotide ligand molecules with a unique three-dimensional shape, capable of binding to a defined molecular target with high affinity and specificity. Since their discovery, aptamers have been developed for various applications, including molecular imaging, particularly nuclear imaging that holds the highest potential for the clinical translation of aptamer-based molecular imaging probes. Their easy laboratory production without any batch-to-batch variations, their high stability, their small size with no immunogenicity and toxicity, and their flexibility to incorporate various functionalities without compromising the target binding affinity and specificity make aptamers an attractive class of targeted-imaging agents. Aptamer technology has been utilized in nuclear medicine imaging techniques, such as single photon emission computed tomography (SPECT) and positron emission tomography (PET), as highly sensitive and accurate biomedical imaging modalities towards clinical diagnostic applications. However, for aptamer-targeted PET and SPECT imaging, conjugation of appropriate radionuclides to aptamers is crucial. This review summarizes various strategies to link the radionuclides to chemically modified aptamers to accomplish aptamer-targeted PET and SPECT imaging.

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INTRODUCTION: It has been recognized that serotonin plays a main role in various pathological conditions such as anxiety, depression, aggressiveness, schizophrenia, suicidal behavior, panic and autism. 1-(2-Methoxyphenyl) piperazine pharmacophore, a fragment of the true 5-HT(1A) antagonist WAY100635, is found in numerous selective 5-HT(1A) imaging agents. In this paper, we have reported the synthesis of a novel derivative of 1-(2-methoxyphenyl) piperazine that is labeled with (99m)Tc (CO)(3) via click chemistry. METHODS: The bidentate alkyne, propargylglycine was reacted with phenyl piperazine triazole derivative in the presence of a catalytic amount of Cu (I) to form tridentate ligand. The ligand was radiolabeled with the precursor [(99m)Tc] [(H(2)O)(3) (CO)(3)](+) and characterized by HPLC. The bioevaluation of radio labeled ligand was carried out in rats. RESULTS: Triazole complex was labeled by (99m)Tc-tricarbonyl and its radiochemical yield was more than >95% which was determined by HPLC. In vivo stability studies in human serum albumin show a 93% ratio of complex after a 24h period. The calculated partition coefficient (logP) was 0.34±0.02. Receptor binding assays indicated about 70% specific binding of radioligand to 5-HT(1A) receptors. Biodistribution studies have shown brain hippocampus uptake of 0.40±0.08 %ID/g at 30 min post injection. CONCLUSIONS: Results indicate that this (99m)Tc-tricabonyl-arylpiperazine derivative has specific binding to 5-HT(1A) receptors and presented suitable characters for its use as a CNS imaging agent.

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