Evaluation of 99mTc‐immunoglobulins for imaging infection in the rat

Three immunoglobulin molecules were evaluated as infection imaging agents in a rat model of S. aureas infection: ^99mTc‐infliximab, ^99mTc‐human immunoglobulin (HIG) and ^99mTc‐rat immunoglobulin (RIG). Infliximab is a chimeric monoclonal antibody specific for human tumour necrosis factor alpha (TNFα). ^99mTc‐HIG was chosen as an exogenous protein and ^99mTc‐RIG as an endogenous marker. Each immunoglobulin was treated with 2‐mercaptoethanol and the reduced antibody was isolated by size exclusion chromatography. In combination with Sn^II‐methylenediphosphonic acid, cold kit formulations were prepared. Native and reduced infliximab were tested for rat TNFα binding ability in vitro. A focal intramuscular infection of S. aureus (1 × 10⁸ colony forming units) was induced in the left thigh muscle of rats, that developed for 24 h. In separate experiments each tracer was administered by intravenous injection, then whole body scintigraphic imaging and biodistribution studies were performed at 1 and 4 h later. ^99mTc‐infliximab, ^99mTc‐HIG and ^99mTc‐RIG were prepared with ?95% radiochemical purity from stable cold kits. Results from the organ assay gave infected (target) to non‐infected (control) muscle ratios for ^99mTc‐infliximab as 5.7±0.8, 7.1±1.2, ^99mTc‐HIG gave 3.1±1.1, 7.8±1.2, and ^99mTc‐RIG 7.9±0.3, 12.5±1.5 at 1 and 4 h, respectively. Infliximab and Sn^II‐infliximab did not bind to rat TNFα by the in vitro assay. Although lacking specific affinity for TNFα, ^99mTc‐infliximab accumulated at infectious sites in vivo. ^99mTc‐infliximab gave similar infection uptake ratios to ^99mTc‐HIG at 1 and 4 h, but these proteins were inferior in comparison to ^99mTc‐RIG, and is likely to be due to increased clearance associated with the foreign protein structure. Copyright © 2006 John Wiley & Sons, Ltd.     

99mTc‐anti‐epidermal growth factor receptor nanobody for tumor imaging

Nanobodies are important biomolecules for tumor targeting. In this study, we synthesized and labeled anti‐epidermal growth factor receptor (EGFR) nanobody OA‐cb6 with ^99mTc(CO)₃⁺ and evaluated its characteristics for targeting the EGFR in the A431 human epidermal carcinoma cell line. Nanobody radiolabeling was achieved with high yield and radiochemical purity, and the radioconjugate was stable. Biodistribution results in nude mice exhibited a favorable tumor‐to‐muscle ratio at 4‐hr postinjection, and tumor location was visualized at 4 hr after injection of radiolabeled nanobody. Our result showed that the OA‐cb6‐^99mTc‐tricarbonyl radiolabeled nanobody is a promising radiolabeled biomolecule for tumor imaging in cancers with high EGFR overexpression.     

A 99mTc‐tricine‐HYNIC‐labeled peptide targeting the neurotensin receptor for single‐photon imaging in malignant tumors

In this study, a new neurotensin (NT) analog was labeled with ^99mTc via HYNIC chelator and tricine as coligand and investigated further. An NT (7–13) analog was prepared, and labeling with ^99mTc was performed. The internalization rate and biodistribution of radiopeptide were studied in HT‐29 cells and nude mice bearing tumor, respectively. Radiolabeling with ^99mTc was performed at high specific activities (54 MBq/nmol) with an acceptable labeling yield (>95%). In vitro cell line studies showed a specific internalization uptake up to 13.23 ± 0.45% during 4 h which was blocked in the presence of excess cold peptide to 0.83 ± 0.15%. In biodistribution studies, uptake was observed in NT receptor‐positive organs so that after 1 h the uptakes in mouse intestine and tumor were 1.23 ± 0.16% ID/g and 1.12 ± 0.11% ID/g, respectively. In animals co‐injected with excess cold peptide, reduction uptake in tumor and intestines were 73% (1.10% vs. 0.29% ID/g at 4 h) and 61% (1.22% vs. 0.47% ID/g at 4 h) respectively. Predominant renal excretion pathway with a highest accumulation of activity in bladder was observed for this radiopeptide. This radiolabeled peptide could be a candidate for detection of NT positive tumors.     

Synthesis and evaluation of a 99mTc‐labeled tubulin‐binding agent for tumor imaging

Cholchicine and its derivatives are very potent tubulin‐binding compounds and can be used as a potential tumor targeting agents. In this study, colchicine was labeled with ^99mTc via hydrazinonicotinic acid (HYNIC) and was investigated further. HYNIC/cholchicine was synthesized and labeling with ^99mTc was performed at 95 °C for 15 min and radiochemical analysis included HPLC method. The stability of radiconjugate was checked in the presence of human serum at 37 °C up to 24 h. Biodistribution was studied in breast tumor‐bearing mice. Labeling yield of 95.8 ± 0.54% was obtained corresponding to a specific activity of 54 MBq/µmol. Radioconjugate showed good stability in the presence of human serum. Biodistribution studies in tumor‐bearing mice showed that ^99mTc/HYNIC/colchicine conjugate accumulated in tumor with good uptake (3.17 ± 0.14% g/g at 1 h post‐injection). The radioconjugate was cleared fast from normal organs and showed clearance through urinary and hepatobiliary systems with accumulation of activity in kidneys and intestine. This radioconjugate may be useful to assess the presence of tumor by imaging.     

Quality control methods for 99mTc‐labeled exogenous natural surfactant (99mTc‐ENS)

To standardize the quality control for ^99mTc‐ENS, the following methods were studied: (1) physical properties and pH, (2) radiochemical purity (chromatographic studies on Whatman‐1 paper, or instant thin‐layer chromatography and solvent extraction using different solvents and (3) rat biodistribution studies by intratracheal injection. The tolerance limits were fixed for each method. The radiopharmaceutical stability was also evaluated. The results showed that ^99mTc‐ENS was a white suspension with a pH between 4.0 and 6.0. The limit for radiochemical impurities in Whatman‐1 paper/acetone was fixed at lower than 2% and the established limit for the organic aliquot in cyclohexane extraction was greater than 2%. In the biodistribution studies, the limits for activity concentration were fixed at greater than 90% for lungs, less than 9% for the gastrointestinal system and less than 1% for the sum of the other organs studied. After a storage time of 6 h at room temperature or in a refrigerator, ^99mTc‐ENS physical properties and pH, radiochemical and biodistribution results were within the established values. In conclusion, the quality control methods for ^99mTc‐ENS are tests on physical properties and pH, radiochemical purity by Whatman‐1 paper/acetone chromatography and cyclohexane extraction and biodistribution studies in rats. The stability of this radiopharmaceutical is at least 6 h at room temperature. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis of 99mTc‐labeled organo‐germanium nanoparticles and their in vivo study as a spleen imaging agent

^99mTc‐Labeled organo‐germanium nanoparticles ranging in size from 60 to 80 nm were newly developed for a spleen imaging agent. The radiolabeled nanoparticles were prepared with a high labeling efficiency (over 99%) and they also showed an excellent stability at room temperature for 6 h. The biodistribution data of the nanoparticles injected into rats via intravenous routes showed a notably higher accumulation in the spleen when compared to other reticuloendothelial system organs. Gamma image of the rabbits obtained after an intravenous injection of the nanoparticles revealed a localization of the radioactivity mainly in the spleen and the liver. Copyright © 2006 John Wiley & Sons, Ltd.     

99mTc‐labeled NGR‐chlorambucil conjugate, 99mTc‐HYNIC‐CLB‐c(NGR) for targeted chemotherapy and molecular imaging

Targeted delivery of chemotherapeutic drug at the tumor site enhances the efficacy with minimum systemic exposure. Towards this, drugs conjugated with peptides having affinity towards a particular molecular target are recognized as affective agents for targeted chemotherapy. Thus, in the present study, tumor‐homing asparagine‐glycine‐arginine (NGR) peptide ligand was conjugated to DNA alkylating nitrogen mustard, chlorambucil (CLB). The peptide‐drug conjugate (PDC), CLB‐c(NGR), was radiolabeled with ^99mTc‐HYNIC core to trace its pharmacokinetics and biodistribution pattern. In vitro cell‐binding studies of ^99mTc‐HYNIC‐CLB‐c(NGR) were conducted in murine melanoma B16F10 cells. The cytotoxicity studies conducted by incubation of the peptide/drug/PDC with B16F10 cells demonstrated enhanced cytotoxic effect of PDC in comparison to either the peptide or the drug alone. In vivo biodistribution studies in C57BL6 mice bearing melanoma tumor showed maximum tumor uptake at 30 minutes pi (2.45 ± 0.28% ID/g), which reduced to 0.77 ± 0.1% ID /g at 3 hours pi. The radiotracer being hydrophilic cleared rapidly from the heart, lungs, liver, and muscle. The tumor‐to‐blood and tumor‐to‐muscle ratios improved with time. This study opens avenues for conjugation of other targeting peptides with the drug CLB for enhanced toxicity at the diseased site.     

Labeling and evaluation of 99mTc‐tricarbonyl‐meloxicam as a preferential COX‐2 inhibitor for inflammation imaging

Imaging of inflammation has an important role in dissolving problems in diagnosis and therapy of patients with inflammatory disorders. In this study meloxican as a nonsteroidal anti‐inflammatory drug (NSAID) has been labeled with thechnetium‐99m‐tricarbonyl core ([^99mTc (CO)₃ (H₂O)₃]⁺) in order to evaluate its feasibility as an inflammation imaging agent for in vivo use. ^99mTc‐tricabonyl labeling of meloxicam was performed by its incubation with prepared precursor ^99mTc‐tricabonyl and heating in a boiling water bath for 30 min while various range of pH (1–9) was adjusted. The stability of ^99mTc‐tricarbonyl‐Meloxicam was checked in human serum at 37 °C, and biodistribution was studied in mice. Labeling yield of 98.1 ± 0.4% was obtained corresponding to a specific activity of 0.14 GBq/µmol. The radioconjugate showed good stability in human serum. Our main achievement was high accumulation of ^99mTc‐tricarbonyl‐Meloxicam in the inflammated muscle in mice (T/NT = 3.90 at 4 h post injection) which may diagnostically be beneficial for distinguish sites of inflammation.     

Synthesis and preliminary biological evaluation of a 99mTc‐labeled hypericin derivative as a necrosis avid imaging agent

Mono‐[¹²³I]iodohypericin and mono‐[¹²³I]iodohypericin monocarboxylic acid are iodine‐123‐labeled hypericin derivatives which have shown great promise in preclinical studies as necrosis avid imaging agents in animal models of infarction. In view of the more attractive properties of a ^99mTc‐labeled hypericin derivative, we have synthesized a conjugate of protohypericin monocarboxylic acid with S‐benzoylmercaptoacetyldiglycyl‐diaminopentane in an overall yield of 15%. The conjugate was labeled with technetium‐99m by exchange labeling at pH 10 in a labeling yield of 95% followed by photocyclization to yield ^99mTc‐mercaptoacetyldiglycyl‐1,5‐diaminopentylene hypericincarboxamide (^99mTc‐13). The negatively charged ^99mTc‐13 complex was purified by reversed phase high‐pressure liquid chromatography and the log P_7.4 was determined to be 2.36. In normal NMRI mice, the complex showed slow hepatobiliary clearance while plasma clearance was rapid. The tracer was evaluated in rats with reperfused hepatic infarction by ex vivo autoradiography, gamma counting and histochemical techniques. Unlike the radioiodinated hypericin derivatives, the new tracer agent did not show preferential uptake in necrotic tissue on autoradiography and gamma counting techniques. Conjugation of hypericin with a ^99mTc‐chelate, resulting in a change in size, charge and lipophilicity, had a profound effect on the necrosis avidity of the tracer agent. The results show that ^99mTc‐13 is not suitable for imaging necrosis. Copyright © 2008 John Wiley & Sons, Ltd.     

99mTc‐labeled DTPA‐colchicine dimer with improved tumor uptake

This work reports the synthesis, radiolabeling, and biological studies of ^99mTc‐diethylene triamine pentaacetic acid (DTPA)‐colchicine dimer in tumor‐bearing mice. The novel colchicine dimer was successfully synthesized by conjugation of DTPA to 2 colchicine biomolecules. The ligand could be labeled by ^99mTc in high yield to get ^99mTc‐DTPA‐colchicine dimer, which was hydrophilic and stable at room temperature. Biodistribution and imaging studies in tumor‐bearing mice showed that ^99mTc‐DTPA‐colchicine dimer accumulated in the tumor with improved uptake and retention. The results indicate the need for synthetic modification of the parent colchicine derivative and the ^99mTc‐chelate with a view to improve the tumor‐targeting efficacy and in vivo kinetic profiles.     

Synthesis and biological evaluation of a series of 99mTc‐labeled diphosphonates as novel radiotracers with improved bone imaging

Three radiolabeled diphosphonates, ^99mTc‐labeled 1‐hydroxy‐3‐(2‐propyl‐1H‐imidazol‐1‐yl)propane‐1,1‐diyldiphosphonic acid (PIPrDP), 1‐hydroxy‐4‐(2‐propyl‐1H‐imidazol‐1‐yl)butane‐1,1‐diyldiphosphonic acid (PIBDP), and 1‐hydroxy‐5‐(2‐propyl‐1H‐imidazol‐1‐yl)pentane‐1,1‐diyldiphosphonic acid (PIPeDP), have been designed and synthesized with good chemical yields and high radiochemical purity. Their in vitro and in vivo biological properties were investigated and compared. All radiotracers evaluated in mice showed substantial retention in bone (8.42 ± 0.53, 9.08 ± 0.65, and 10.3 ± 0.61 ID%/g, respectively) at 1 h post‐injection and had rapid clearance in blood (1.9484, 1.3666, and 0.7704 ID%/g/min, respectively). ^99mTc‐PIBDP has the highest uptake ratio of bone‐to‐soft tissue at 1 h post‐injection among the three radiotracers. The results indicate that ^99mTc‐PIBDP is the most promising bone imaging agent. Copyright © 2012 John Wiley & Sons, Ltd.     

Synthesis and preliminary evaluation of a 99mTc‐labeled folate‐PAMAM dendrimer for FR imaging

Folate receptor is an ideal target for tumor‐specific diagnostic and therapeutic. The aim of this study was to synthesize ^99mTc‐labeled folate‐polyamidoamine dendrimer modified with 2‐hydrazinonicotinic acid (^99mTc‐HP ₃FA ) for FR imaging. The ^99mTc‐HP ₃FA conjugate was prepared using N‐tris‐(hydroxymethyl)‐methylglycine and trisodium triphenylphosphine‐3,3′,3″‐trisulfonate as coligands. Physicochemical properties, in vitro cell uptake study, and in vivo micro‐single‐photon emission computed tomography/CT imaging were performed. The radiolabeled ^99mTc‐HP ₃FA conjugate was prepared with high radiolabeling yield, good stability, and water solubility (logP  = ?1.70 ± 0.21). In cell uptake study, the radiolabeled conjugate showed high uptakes in the FR ‐abundant KB cells and could be blocked significantly by excess folic acid. The 7721 cells which served as control group substantially had no uptakes. The results of micro‐single‐photon emission computed tomography/CT imaging exhibited that high accumulation of activity was found in FR ‐overexpressed KB tumor, and the tumor‐to‐muscle ratio was approximately 25.78, while, using free FA as inhibitor, the uptakes of ^99mTc‐HP ₃FA in KB tumor and kidney were obviously inhibited. In summary, a new radiocompound was synthesized successfully with specific FR targeting ability. The feasibility of ^99mTc‐HP ₃FA for early diagnosis of FR ‐positive tumors with non‐invasive single‐photon emission computed tomography imaging was demonstrated and the possibility of imaging‐guided drug delivery based on multifunctional polyamidoamine will be studied in the future.     

Synthesis and biodistribution of novel 99mTc‐nitrido methylpiperidine dithioformate derivatives as potential brain imaging agents

Three dithioformate ligands with methyl substituted on the piperidine rings, potassium 1‐(2‐methylpiperidine‐1‐yl)‐dithioformate (2‐mp), potassium 1‐(3‐methylpiperidine‐1‐yl)‐dithioformate (3‐mp) and potassium 1‐(4‐methylpiperidine‐1‐yl)‐dithioformate (4‐mp) were synthesized. The corresponding ^99mTc‐nitrido complexes were prepared in high yield (>95%) through the [^99mTcN] intermediate and characterized by thin layer chromatography and high‐performance liquid chromatography. All the neutral ^99mTc‐nitrido complexes were stable under physiological conditions and lipophilic with log P values between 1.40 and 1.58. In vivo biodistribution results showed that all the ^99mTc‐nitrido complexes displayed high brain uptakes and long retention times. Among them, ^99mTcN‐4mp, demonstrated the best properties for brain imaging with the brain uptake 3.40±0.24, 3.22±0.31, 2.72±0.28 and 2.22±0.18% ID/g at 5, 30, 60 and 120 min p.i., respectively. Moreover, the influence of stereochemistry of the ^99mTcN complexes with methyl substitution on ortho, meta and para positions on piperidine ring on the biodistribution properties were investigated with B3LYP/6‐31G*(LANL2DZ for Tc) method using the Gaussian 03 program package. Copyright © 2009 John Wiley & Sons, Ltd.     

Red blood cells labelling with 99mTc‐d,l‐HMPAO: an alternative method for specific cases

The effectiveness of the classic methods for red blood cells (RBCs) labelling with ^99mTc has been demonstrated in nuclear medicine. However, nuclear physicians have found, in certain circumstances, this diagnostic technique fails and poor quality images are obtained. In this work we report on an alternative method that is of useful in these occasions, for in vitro labelling RBCs with ^99mTc‐d,l‐HMPAO complex. The study shows a high and reproducible labelling efficiency (94.14±0.38), using low amount of tin. The RBCs were isolated from plasma and other interfering blood cells before adding ^99mTc‐d,l‐HMPAO. The tracer was retained and the elution rate from RBCs was low (less than 6% after 120 min). The preclinical results indicate that this new method could be a good alternative to the standard classic methods for specific cases. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis,characterization and pre‐clinical evaluation of 99mTc‐tricarbonyl complexes as potential myocardial perfusion imaging agents

Myocardial perfusion imaging is an established Nuclear Medicine investigation. Current myocardial perfusion imaging agents sestamibi and tetrofosmin have number of drawbacks; low heart uptake coupled with uptake into the surrounding tissues leads to a poorer image quality. There is a need for continued research into designing and evaluating potentially superior myocardial imaging agents. Tri‐carbonyl‐technetium and rhenium complexes were prepared by combination with mono‐dentate and bi‐dentate ligands. Complexes were characterized by HPLC, MAS, nuclear magnetic resonance, infrared, single‐crystal X‐ray diffraction and partition coefficient determinations. ^99mTc(CO)₃ complexes were administered intravenously to Sprague Dawley rats, and tissue distribution studies were carried out at 15 min and 1 h p.i. Radiochemical purity was assessed as >90%. 1‐10‐phenanthroline, 2,2′‐bipyridine and imidazole complexes gave the highest heart uptake. The percentage injected dose per gram (n = 3) at 1 h for 1‐10‐phenanthroline/imidazole was blood 0.21 ± 0.01, heart 1.12 ± 0.11, kidney 3.61 ± 1.13, liver 0.62 ± 0.06, lung 0.28 ± 0.12, spleen 0.24 ± 0.05, small intestine contents 1.87 ± 0.92; and for 2,2′‐bipyridine /imidazole was blood 0.23 ± 0.02, heart 1.07 ± 0.18, kidney 3.31 ± 1.28, liver 0.56 ± 0.09, lung 0.14 ± 0.02, spleen 0.2 ± 0.1, small intestine content 1.05 ± 0.48. Further investigation to evaluate more complexes based on 1,10‐phenanthroline, 2,2′‐bipyridine and imidazole derivatives could potentially lead to agents with an increased heart uptake and faster clearance from the liver and gastrointestinal tract.     

Preparation and biological evaluation of 99mTcN‐labeled pteroyl‐lys derivative as a potential folate receptor imaging agent

In order to develop a novel ^99mTc‐labeled folate receptor (FR) imaging agent, a dithiocarbamate derivative, pteroyl‐lys‐DTC, was synthesized and radiolabeled with ^99mTc through the [^99mTcN]²⁺ intermediate. The radiochemical purity of the corresponding ^99mTc‐complex, ^99mTcN‐pteroyl‐lys‐DTC, was over 95% as measured by reversed‐phase HPLC. The ^99mTcN complex was stable under physiological conditions. ^99mTcN‐pteroyl‐lys‐DTC exhibited specific FR binding in FR‐positive KB cells in vitro. The biodistribution in tumor‐bearing mice showed that the ^99mTcN‐labeled radiotracer had good uptake (3.56 ± 0.09%ID/g at 2 h postinjection) in FR‐positive KB tumors, as well as in the kidneys (30.34 ± 3.53%ID/g at 2 h postinjection). After coinjection with excess folic acid, the uptake in tumor and kidneys was significantly blocked. The results indicated that ^99mTcN‐pteroyl‐lys‐DTC was able to target the FR‐positive tumor cells and tissues specifically both in vitro and in vivo. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis and pharmacological evaluation of 99mTc‐labeled imidazolyl‐containing diphosphonic acid as a novel bone imaging agent

In order to develop a superior bone imaging agent, a new radiotracer ^99mTc‐1‐hydroxy‐5‐(2‐butyl‐1H‐imidazol‐1‐yl)pentane‐1,1‐diyldiphosphonic acid (BIPeDP) was designed and prepared with good radiochemical yield and stability. The biodistribution in mice shows that ^99mTc‐BIPeDP has high specificity in the skeleton with the maximum uptake of 17.30 ± 0.14 injected dose per gram at 60 min. Kinetics of blood clearance shows that the distribution half‐life (T_1/2α) and elimination half‐life (T_1/2β) of ^99mTc‐BIPeDP are 3.7 and 49.7 min, respectively. An excellent image can be obtained at 1‐h post‐injection with the single photon emission computed tomography bone scanning, which is clearer and quicker than ^99mTc‐zoledronic acid, ^99mTc‐1‐hydroxy‐5‐(1H‐imidazol‐1‐yl)pentane‐1,1‐diyldiphosphonic acid, and ^99mTc‐methylenediphosphonic acid All results indicate that ^99mTc‐BIPeDP holds great potential as a novel promising bone imaging agent. Copyright © 2013 John Wiley & Sons, Ltd.     

Development of a novel 99mTc‐labeled small molecular antagonist for CXCR4 positive tumor imaging

The chemokine receptor 4 (CXCR4) has been an attractive molecular target for tumor imaging, because it is overexpressed in many tumor types and involved in tumor progression and metastasis. The purpose of this study is to examine the CXCR4 targeting properties of ^99mTc‐labeled AMD3465, a small molecule antagonist of CXCR4. ^99mTc‐AMD3465 was prepared in high yield (>95%) and stable in mice serum at least for 4 hours. In vitro cell binding experiments were performed with Chinese hamster ovary (CHO), MCF‐7 (breast cancer), and CHO‐CXCR4 (CHO stably transfected to express CXCR4) cell lines. Small animal single photon emission computed tomography/computed tomography imaging studies in nude mice bearing MCF‐7 and CHO xenografts showed that the uptakes of the radiotracer in MCF‐7 tumors were significantly higher than those in the CXCR4‐negative CHO tumors (P < 0.05), and the MCF‐7 tumors uptake could be blocked with an excess of unlabeled AMD3465 (P < 0.05). These results suggested that ^99mTc‐AMD3465 could be a potential single photon emission computed tomography radiotracer for CXCR4 imaging.     

Improved synthesis and biological evaluation of Tc‐99m radiolabeled AMO for miRNA imaging in tumor xenografts

MicroRNAs (miRNAs) have been considered as important biomarkers for malignant tumors. In this study, we introduced an improved ^99mTc labeling method for noninvasive visualization of overexpressed miRNAs in tumor‐bearing mice. Anti‐miRNA‐21 oligonucleotide (AMO) with partial 2′‐O‐methyl and phosphorothioate modification was designed and chemically synthesized. After conjugated with NHS‐MAG3, AMO was labeled with ^99mTc. Optimization was made to shorten reaction time and to improve labeling efficiency. Labeling efficiency was 97%, and specific activity was 2.78 MBq/ng. During 12 h, ^99mTc‐AMO showed no significant degradation by gel electrophoresis. Its radiochemical purity was stable, between 95.8% and 99.1%. Further, ^99mTc‐AMO decreased the level of miR‐21 and increased the expression of PTEN protein at cellular level, shown by qRT‐PCR and Western blot. Fluorescent protein labeled AMO displayed specific distribution and good stability in tumor cells. After the administration in tumor‐bearing mice, ^99mTc‐AMO showed more radioactive uptake in the miR‐21 over‐expressed tumors than scramble control. Biodistribution results further proved the significant difference of tumor uptake between ^99mTc‐AMO and ^99mTc‐control. Therefore, this study presents an improved method with shorten time to prepare a ^99mTc radiolabeled AMO. In addition, it supports the role of ^99mTc‐AMO for noninvasive visualization of miR‐21 in malignant tumors.     

Synthesis and radiobiological evaluation of a new 99mTc‐labeled small peptide: 99mTc‐YGGSLAK as imaging agent

Peptides are known as receptor‐specific molecules that play an important role not only in diagnosis and therapy of neoplastic diseases, but also in the pathogenesis of other diseases. In an effort to develop a peptide‐based radiopharmaceutical for scintigraphic studies, a small peptide Tyr‐Gly‐Gly‐Ser‐Leu‐Ala‐Lys (YGGSLAK) was synthesized by Fmoc solid‐phase peptide synthesis using an automated synthesizer. This peptide was analyzed by TLC, HPLC and mass spectroscopy. Then, we investigated its analytical and pharmacokinetic study after radiolabeling with technetium‐99 m (^99mTc) using SnCl₂. The radiochemical purity of the complex was over 95% and log p value was 1.46. In vivo biodistribution studies in rat showed that most activity of this injected radiolabeled peptide (^99mTc‐YGGSLAK) was accumulated in the liver and followed by gallbladder, intestines and kidney. Scintigraphy studies on rabbits also showed very high uptake and retention in the liver and gallbladder, and after 1 h slowly excreted through the hepatobiliary system and a little amount was also excreted through the renal system. The radiochemical and in vitro and in vivo characterization indicates that ^99mTc‐YGGSLAK has certain favorable properties and it might be used as a new radiopharmaceutical for hepatobiliary scintigraphy. Copyright © 2011 John Wiley & Sons, Ltd.