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Introduction: Iranian scorpion species are classified in Buthidae and Scorpionidae with 16 genera and 25 species. In Iran, similar to other parts of the world, there are a few known species of scorpions responsible for severe envenoming. Mesobuthus eupeus is the most common species in Iran. Its venom contains several toxin fractions which can affect the ion channel. In this study purification, labeling and biological evaluation of Mesobuthus eupeus scorpion venom are described. Methods: To separate different venom fractions, soluble venom was loaded on a chromatography column packed with sephadex G50 gel then the fractions were collected according to UV absorption at 280 nm wavelength. Toxic fraction (F3) was loaded on anionic ion exchanger resin (DEAE) and then on a cationic resins (CM). Finally toxic fraction F319 was labeled with 99mTc and radiochemical analysis was determined by paper chromatography. The biodistribution was studied after injection into normal mice. Results: Toxic fraction of venom was successfully obtained in purified form. Radiolabeling of venom was performed at high specific activity with radiochemical purity more than 95% which was stable for more than 4 h. Biodistribution studies in normal mice showed rapid clearance of compound from blood (2.64% ID at 4 h) and tissues except the kidneys (27% ID at 4 h). Conclusion: As tissue distribution studies are very important for clinical use, results of this study suggest that 99mTc labeling of venom can be a useful tool for in vivo studies and is an excellent approach to follow the process of biodistribution and kinetics of toxins. [ABSTRACT FROM AUTHOR]

PR81 is a monoclonal antibody that binds with high affinity to MUC1, which is over expressed on breast and other tumors. The objective of this study was to compare the two labeling methods (direct and indirect radioiodination) for application of this antibody against MUC1 as a radioimmunotherapeutical agent.Monoclonal antibody (PR81) against the tandem repeat of the core protein (MUC1) was prepared, characterized, purified, and labeled with ^{131}I using the direct (chloramin-T) and indirect (Fmoc-D-Tyr (tBu)-D-Tyr (tBu)-D-Lys (Boc)-OH (YYK) attached to N-hydroxysuccinimide as a linker between PR81 and ^{131}I) methods. The immunoreactivity of ^{131}I-PR81 and ^{131}I-TP-PR81 complexes with MUC1 (the native protein), BSA-P_{20} (a 20 amino acid corresponding the tandem repeat of MUC1) and MCF7 cell line were performed by RIA. In vitro stability of ^{131}I-PR81 and ^{131}I-YYK-peptide-PR81 complexes in human serum was determined by thin layer chromatography (TLC). Cell toxicity and in vitro internalization studies were performed with the MCF7 cell line, and the tissue biodistribution of the ^{131}I-PR81 and ^{131}I- YYK-peptide -PR81 complexes was evaluated in normal BALB/c mice at 4, 24 and 48 hrs. The labeling efficiency was determined by measuring the percentage recovery of radioactivity in the final product relative to the initial activity in the shipment vial, was found to be 59.9% ± 7.9% for direct and 50% ± 3.2% for indirect methods. ^{131}I-PR81 and ^{131}I- YYK- peptide -PR81 complexes showed high immunoreactivity towards MUC1 protein, BSA-P_{20} and MCF7 cell line. In vitro stability of the labeled products in human serum which was measured by thin layer chromatography (TLC) was found to be more than 50% over 24 hr for ^{131}I-PR81 and 70% for ^{131}I- YYK-peptide -PR81 complexes. Cell toxicity and in vitro nternalization studies showed that the ^{131}I-PR81 and ^{131}I- YYK-peptide -PR81 complexes inhibited 80% growth of the MCF7 cultured cell lines in vitro in a high concentration and up to 40% of the ^{131}I-PR81 and 60% of the ^{131}I- YYK-peptide -PR81 complexes internalized after 24 h. Biodistribution studies were performed in normal BALB/c mice at 4, 24 and 48 hrs post-injection. Thyroid and stomach levels from PR81 labeled with ^{131}I- YYK-peptide were two- to three- fold less than those with directly labeled ^{131}I-PR81, suggesting low recognition of its D-iodotyrosine residue by endogenous deiodinase. These results show that the indirect labeling was better than the indirect labeling and ^{131}I- YYK-peptide -PR81 may be considered as a promising candidate for therapy of breast cancer. [ABSTRACT FROM AUTHOR]

Introduction: Bombesin (BN), a 14-amino acid neuropeptide, shows high affinity for the human GRP (gastrin releasing peptide) receptors, which are overexpressed by a variety of cancers, including prostate, breast, pancreas, gastrointestinal, and small cell lung cancer. Aim was to prepare [6-hydrazinopyridine-3-carboxylic acid (HYNIC0), D-Tyr6, D-Trp8] - BN [6-14] NH2 that could be easily labeled with 99mTc and evaluation of its potential as an imaging agent. Methods: Synthesis of the peptide amide was carried out onto Rink Amide MBHA (4-Methylbenzhydrylamine) resin. A bifunctional chelating agent (BFCA) was attached to the N terminal peptide in solid-phase. 99mTc labeling was performed by addition of sodium pertechnetate to solution that include [HYNIC0, D-Tyr6, D-Trp8] Bombesin [6-14] NH2, tricine, ethylenediamine-N,N′-diacetic acid (EDDA) and SnCl2. Radiochemical evaluation was carried out by reverse phase high-performance liquid chromatography (HPLC) and instant thin layer chromatography (ITLC). In-vitro internalization was tested using human prostate cancer cells (PC-3) with blocked and non-blocked receptors. Biodistribution was determined in rats. Results: [99mTc/tricine/EDDA-HYNIC0, D-Tyr6, D-Trp8] bombesin [6-14] NH2 was obtained with radiochemical purities >98%. Results of in-vitro studies demonstrated a high stability in serum and suitable internalization. Biodistribution data showed a rapid blood clearance, with renal excretion and specific binding towards GRP receptor-positive tissues such as pancreas. Conclusion: In this study, labeling of this novel conjugate with 99mTc easily was performed using coligand. The prepared 99mTc-HYNIC-BN conjugate has promising characteristics for the diagnosis of malignant tumors. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Ubiquicidin (UBI) 29–41 is a cationic synthetic antimicrobial peptide fragment that binds preferentially with the anionic microbial cell membrane at the site of infection. This study was conducted to evaluate the potentiality of [99mTc/Tricine/HYNIC0]UBI 29–41 prepared from lyophilized kits as an infection imaging agent in humans. Methods: Seven patients (5 males and 2 females; mean age=55 years; age range=35–75 years) with suspected bone or soft-tissue infections participated in this study. [99mTc/Tricine/HYNIC]UBI 29–41, corresponding to activity in the range 555–740 MBq added to 40 μg of peptide obtained from instant freeze-dried kit formulations with radiochemical purities >95%, was injected intravenously. A 45-min dynamic study was followed by spot views of the suspected region of infection (target) and a corresponding normal area (nontarget). Whole-body anterior and posterior images were also acquired at 30, 60 and 120 min after injection. True- or false-positive or true- or false-negative images were interpreted upon bacterial culture, radiography, clinical tests and bone scanning. Results: The biodistribution of [99mTc/Tricine/HYNIC]UBI 29–41 in patients showed rapid accumulation of activity in the kidneys in the first 30 min after injection that gradually declined and accumulated in the urinary bladder. There were positive findings in five studies and negative findings in two. Findings were subsequently confirmed to be true positive or negative. Images showed minimal accumulation in nontarget tissues, with an average target/nontarget ratio of 2.10±0.33 in positive lesions at 30 min. Conclusion: Given its favorable clinical characteristics, [99mTc/Tricine/HYNIC]UBI 29–41 shows promise as a tracer for infection imaging that allows early diagnosis (30 min) of infection. [Copyright &y& Elsevier]

Introduction: Over expression of selected peptide receptors in human tumors has been shown to represent clinically relevant targets for cancer diagnosis and therapy. The aim of this work was to investigate Neuropeptide Y (NPY) as a new radiopharmaceutical for diagnosis of breast cancer. Methods: A neuropeptide Y analogues with Y1 receptor preference and agonistic properties was synthesized by solid phase method. After conjugation with diethylenetriaminepentaacetic acid (DTPA) labeling with 111In was performed. For labeled peptide, yield of labeling, stability in human serum, receptor binding in cell surface with internalization in SK-N-MC cells, and biodistribution in normal rat were determined. Results: Peptide was synthesized and labeled with more than 95% purity. Radiolabeled peptide was stable in human serum and specifically binds and internalized in the cells with Y1 receptor (4h = 22%). A rapid clearance from blood pool and urinary with hepatobiliary excretion were observed. Conclusion: Our results showed that this peptide can be considered as a candidate for diagnosis of breast tumors. [ABSTRACT FROM AUTHOR]

Introduction: Ubiquicidin 29-41 (UBI) is a fragment of the cationic antimicrobial peptide that is present in various species including humans. The purpose of this study was to investigate radiochemical and biological characteristics of [6-hydrazinopyridine-3-carboxylic acid (HYNIC)]-UBI 29-41 designed for the labeling with 99mTc using tricine as coligand. Methods: Synthesis was preformed on a solid phase using a standard Fmoc strategy and HYNIC precursor coupled at the N-terminus. Purified peptide conjugate was labeled with 99mTc at 100°C for 10 min, Radiochemical analysis involved ITLC and high-performance liquid chromatography methods. Peptide conjugate stability and affinity to human serum was challenged for 24 hours and its in vitro binding to bacteria was assessed. Biodistribution and accumulation of radiopeptide in staphylococcus aureus infected mice were studied using scintigraphy and ca- vivo counting. Results: Radiolabeling was performed at high specific activities, and radiochemical purity was >95%. The stability of radiolabeled peptide in human serum was excellent. In vitro studies showed 70% of radioactivity was bound to bacteria. After injection into mice with a bacterial infection, removing from the circulation occurred mainly by renal clearance and site of infection was rapidly detected within 30 rain. Target to nontarget muscle ratio was 2.099 ± 0.05% at 30 rain post injection. Conclusion: [99mTc-HYNIC]-UBI 29-41 showed favorable radiochemical and biological characteristics which permitted detection of the infection with optimal visualization within 30 min. [ABSTRACT FROM AUTHOR]

Introduction: Radioimmunotherapy (RIT) is a very promising new therapy for the treatment of recurrent B-Cell non-Hodgkin's lymphoma (NHL). Iodine-131 is the most frequently used nuclide in clinical RIT, but its usefulness has been limited by dehalogenation of monoclunal antibodies labeled via conventional methods. To circumvent this problem, we have synthesized a tri-peptide consisting of nonmetabolizable D amino acids attached to N-Hydroxysuccinimide (NHS). Methods: Tri-peptide was synthesized by standard Fmoc solid phase synthesis ola tritylchluride resin, Labeling of tri-peptide was performed using the chloramine-T method and the conventional extraction. Radioiodination of tri-peptide was followed by conjugation to anti-CD20 antibody. In vitro stability of labeled antibody in serum and phosphate buffered saline (PBS) was measured for 48hr by (thin layer chromatography) TLC. Raji cell line was used to test cell binding of the labeled anti-CD20. Results: The chemical purity of synthesized peptide as assessed by analytical (high performance liquid chromatography) HPLC was 95%. Labeling of tri-peptide resulted in a radiochemical yield of 50-71% with radiochemical purity of > 95%. At Rituximab concentration of 10mg/ml, coupling efficiencies of 65-80% was obtained with radiochemical purity of 95% and Specific activity (SA) of 185MBq/mg (5mCi/mg). Conclusion: This study showed that labeling monoclonal antibodies with radioiodine by non-metabolizable D amino acids will improve bio-stability of the product. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Radiolabeled somatostatin analogues are important tools for the in vivo localization and targeted radionuclide therapy of somatostatin-receptor-positive tumors. The aim of this study was to evaluate a new somatostatin analogue designed for the labeling with 99mTc: [6-hydrazinopyridine-3-carboxylic acid (HYNIC0), 1-Nal3, Thr8]-octreotide ([HYNIC]-NATE), using ethylenediamine-N,N′-diacetic acid (EDDA) and tricine as coligands. Methods: Synthesis was preformed on a solid phase using a standard Fmoc strategy. Labeling with 99mTc was performed at 100°C for 10 min using SnCl2 as a reductant. Radiochemical analysis involved ITLC and high-performance liquid chromatography methods. Peptide conjugate affinity was determined in AR4-2J cell membranes. The internalization and externalization rates were studied in sstr2-expressing AR4-2J cells. Biodistribution of radiopeptide was studied in rats bearing the AR4-2J tumor. Results: Radiolabeling was performed at high specific activities, and radiochemical purity was >95%. Peptide conjugate showed high affinity binding for sstr2. The radioligand showed a moderate and specific internalization into AR4-2J cells (14.13±0.61% at 4 h). In animal biodistribution studies, a receptor-specific uptake of radioactivity was observed in somatostatin-receptor-positive organs. After 4 h, uptake in the AR4-2J tumor was 1.33±0.23%ID/g (percentage of injected dose per gram of tissue). Conclusion: These data show that [99mTc/EDDA/tricine/HYNIC]-NATE is a specific radioligand for the somatostatin-receptor-positive tumors and is a suitable candidate for clinical studies. [Copyright &y& Elsevier]