Preparation and in vivo biological investigation of 99mTc‐HEIDP as a novel radioligand for bone scanning

A novel diphosphonic acid, 1‐hydroxy‐2‐(1‐ethyl‐imidazol‐2‐yl) ethane‐1,1‐diphosphonic acid (HEIDP), was prepared and labeled with ^99mTc in a high labeling yield under optimized labeling conditions. The biodistribution in mice shows that ^99mTc‐HEIDP has high specificity and efficacy in bone and joint uptake with 5.73 and 9.93%ID/g at 5 min, which increases continuously to a maximum of 7.62 and 18.0%ID/g at 30 min, respectively. Kinetics of blood clearance showed that distribution half‐life (T_1/2α) and elimination half‐life (T_1/2β) of ^99mTc‐HEIDP were 9.91 and 81.1 min, respectively. The total clearance rate was 1.94%ID/g?min^‐1. A plain and clear bone image was obtained at 1 h by using single photon emission computed tomography. All results indicate that ^99mTc‐HEIDP holds potential as a superior tracer agent for bone scanning. Copyright © 2012 John Wiley & Sons, Ltd.     

Lactosaminated N‐succinyl‐chitosan as a liver‐targeted carrier of 99mTc in vivo for nuclear imaging and biodistribution

Lactosaminated N‐succinyl‐chitosan (LNSC), a water‐soluble biodegradable derivative of chitosan, was prepared, characterized, and investigated for nuclear imaging and body distribution. The labeling efficiency of LNSC was examined with ^99mTc, and the obtained complex was used as liver‐targeted delivery system in vivo for nuclear imaging, and its biodistribution within the body was studied. The labeling efficiency with ^99mTc was investigated for time of reaction, effect of substrate amount, effect of stannous chloride (SnCl₂) concentration, and effect of the pH of the reaction mixture, in order to approach the optimum condition for labeling technique. It was found that the maximum yield for labeling of 2.5‐mg ^99mTc‐LNSC was 96.9% when 50 µg of SnCl₂ was used at pH 3.5–5, at room temperature and 5‐min reaction time. An in vivo biodistribution study of radiolabeled LNSC was carried out in female Wistar rats, and the body distribution profile was recorded by gamma scintigraphy. The biodistribution of ^99mTc‐labeled LNSC (^99mTc‐LNSC) in each organ was calculated as a percentage of the injected dose per gram of tissue (%ID/g). ^99mTc‐LNSC was shown to be a highly potential approach for liver imaging. Moreover, the rapid excretion of LNSC through the kidneys suggests that water‐soluble chitosan derivatives are good carriers of radioactive elements that do not accumulate in the body. The results indicate that the easy and inexpensive extraction, and thus the ready availability, of chitosan and its derivatives makes them potentially useful for applications in scintigraphic imaging.     

On the 99mTc‐labeling of isoniazid with different 99mTc cores

Recent advances in the chemistry of radiolabeling with ^99mTc such as use of the ^99mTc tricarbonyl and ^99mTc–HYNIC cores have revived interest in ^99mTc‐labeling of small biomolecules and further investigation as potential radiopharmaceuticals. Isoniazid, a drug commonly used for treatment of tuberculosis, has been chosen for the present study. Three distinct strategies were utilized to radiolabel isoniazid with ^99mTc. In the direct labeling protocol, the hydrazino amide functional group of isoniazid was used for ^99mTc‐labeling in the HYNIC sense using tricine and EDDA as co‐ligands. The other strategies of ^99mTc‐labeling involved the derivatization of isoniazid to its N, N‐diacetic acid derivative, which in turn was either used as a tridentate ligand for labeling with the [^99mTc(CO)₃(H₂O)₃]⁺ synthon or directly labeled by the conventional route wherein ^99mTc is in the +3 oxidation state. The complexes prepared in >95% yields were characterized by paper chromatography, thin layer chromatography and HPLC. Comparison of the three approaches showed that maximum specific activity and stability was obtained in the ^99mTc–isoniazid derivative synthesized via the tricarbonyl method. However, in vitro cell‐binding studies indicated that none of the ^99mTc–isoniazid complexes prepared had any appreciable uptake in Mycobacterium tuberculosis. Copyright © 2005 John Wiley & Sons, Ltd.     

Preparation,analysis and biodistribution in mice of iodine‐123 labelled derivatives of hypericin

The synthesis of iodine‐123 labelled mono‐ and di‐iodo derivatives of hypericin, an hydroxylated phenanthroperylenequinone which is used for photodynamic therapy and has been shown to accumulate in several tumour types, is reported. Labelling was performed by electrophilic substitution on hypericin or iodohypericin with [¹²³I]iodide in the presence of peracetic acid and provided both mono‐[¹²³I]iodohypericin and di‐[¹²³I]iodohypericin in good radiochemical yields (>80%). Mono‐[¹²³I]iodohypericin was obtained with a high specific activity (925 GBq/μmol) whereas di‐[¹²³I]iodohypericin was obtained in low specific activity (4 GBq/μmol) due to deiodination and subsequent iodination of iodohypericin which occurred during the labelling reaction. Biodistribution studies in mice showed a slow blood clearance and extensive hepatobiliary clearance as well as faecal excretion for both compounds. They will be further evaluated with regard to their tumor seeking properties. Copyright © 2004 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.     

99mTc‐tazobactam,a novel infection imaging agent: Radiosynthesis,quality control,biodistribution, and infection imaging studies

The radiolabeled drug ^99mTc‐tazobactam (^99mTc‐TZB) was developed and assessed as an infection imaging agent in Pseudomonas  aeruginosa and Salmonella  enterica infection–induced animal models by comparing with inflammation induced animal models. Radiosynthesis of ^99mTc‐TZB was assessed while changing ligand concentration, reducing agent concentration, pH, and reaction time while keeping radioactivity constant (~370 MBq). Percent labeling of the resulting complex was measured using paper chromatography and instant thin layer chromatography. The analysis of the ^99mTc‐TZB complex indicated >95% labeling yield and electrophoresis revealed complex is neutral in nature. The biodistribution study also showed predominantly renal excretion; however liver, stomach, and intestine also showed slight tracer agent uptake. The agent significantly accumulated in Pseudomonas aeruginosa and Salmonella enterica infection induced tissues 3.58 ± 0.26% and 2.43 ± 0.42% respectively at 1 hour postinjection. The inflamed tissue failed to uptake noticeable activity at 1 hour time point. The scintigraphic study results were found in accordance with biodistribution pattern. On the basis of our preliminary results, the newly developed ^99mTc‐TZB can be used to diagnose bacterial infection and to discriminate between infected and inflamed tissues.     

Radiochemical and biological characteristics of 99mTc‐difloxacin and 99mTc‐pefloxacin for detecting sites of infection

The optimization of the radiolabeling yield of ciprofloxacin analogous, difloxacin and pefloxacin, with ^99mTc was described. At pH 4, difloxacin was labeled with ^99mTc with a labeling yield of 95.6% by adding ^99mTc to 5 mg difloxacin in the presence of 100 µg SnCl₂·2H₂O whereas ^99mTc‐pefloxacin was labeled (98.1%) by adding ^99mTc to 4 mg pefloxacin in the presence of 50 µg SnCl₂·2H₂O. The radiochemical purity for both labeled compounds was evaluated with ITLC and HPLC system. Biological distribution of ^99mTc‐difloxacin and ^99mTc‐pefloxacin was carried out in experimentally induced infection rats, in the left thigh, using Staphylococcus aureus. Both thighs of the rats were dissected and counted and the ratio of bacterial infected thigh/contralateral thigh was then evaluated. T/NT for both ^99mTc‐difloxacin and ^99mTc‐pefloxacin was found to be 5.5±0.5 and 4.9±0.3, respectively, which was higher than that of the commercially available ^99mTc‐ciprofloxacin. Copyright © 2010 John Wiley & Sons, Ltd.     

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,radiolabeling and evaluation of a new positively charged 99mTc‐labeled fatty acid derivative for myocardial imaging

¹²³I‐labeled fatty acids and ¹⁸F‐FDG are used as metabolic markers for detecting myocardial abnormalities. However, a ^99mTc‐based molecule may find wider application. In the present work, a new ^99mTc‐labeled, uni‐positively charged, 16‐carbon fatty acid has been prepared and evaluated in normal Swiss mice. The results are then compared with the neutral analogue reported earlier. A 16‐cysteinyl hexadecanoic acid conjugate was synthesized in a six‐step synthetic procedure starting with 16‐bromohexadecanoic acid. The ligand upon incubation with [^99mTcN(PNP6)]²⁺ core formed the required positively charged complex in ～85% yield. The complex, which was obtained as a mixture of syn‐anti isomers, was purified by HPLC and the major fraction was used for in vivo studies in Swiss mice. The biodistribution studies in Swiss mice showed initial uptake similar to ¹²⁵I‐IPPA followed by rapid clearance from the myocardium till 10 min p.i. Thereafter, the rate of clearance was significantly decreased, an observation reported earlier for positively charged fatty acid complexes. In terms of absolute uptake, the positively charged complex performed better than the neutral analogue reported earlier. The positively charged fatty acid complexes, prepared using [^99mTcN(PNP)]²⁺ core, seems to be better candidates for the development of myocardial metabolic tracers than their neutral counterparts. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis and evaluation of two uncharged 99mTc‐labeled derivatives of thioflavin‐T as potential tracer agents for fibrillar brain amyloid

Thioflavin‐T is a fluorescent dye for in vitro detection of fibrillar amyloid β, a protein found in the brain of patients suffering from Alzheimer's disease. We synthesized and biologically evaluated two uncharged ^99mTc‐labeled derivatives of thioflavin‐T. The precursors for labeling were synthesized by coupling an S,S′‐bis‐triphenylmethyl‐N‐tert‐butoxycarbonyl bis‐amino‐bis‐thiol tetradentate ligand via a propoxy spacer to 2‐(4′‐aminophenyl)‐1,3‐benzothiazole at the 6‐position or the 2′‐position. Deprotection and labeling with ^99mTc were done via a one‐pot procedure (15% yield) after which the labeled compound was isolated by high performance liquid chromatography (LC). LC in combination with mass spectrometry (MS) was used for identity confirmation of the labeled compounds. Results of electrophoresis and log P determination supported the assumption that the radiolabeled compounds could cross the blood–brain barrier by passive diffusion. However, in normal mice both compounds showed a low brain uptake 2 min post injection. They were mainly excreted through the hepatobiliary system, with some accumulation in the stomach. Sixty minutes after intravenous injection, 37% of the ^99mTc‐activity in the blood corresponded to the original compound. In view of the low brain uptake, it is concluded that the studied ^99mTc‐labeled derivatives of thioflavin‐T are not suitable as tracer agents for in vivo visualization of amyloid in brain. Copyright © 2009 John Wiley & Sons, Ltd.     

Sodium cholate,a solubilizing agent for the necrosis avid radioiodinated hypericin in rabbits with acute myocardial infarction

Abstract

Objectives: We determined whether sodium cholate (NaCh) could act as a solubilizing agent for the necrosis avid iodine-123-labeled hypericin (¹²³I-Hyp) and investigated biodistribution and targetability of this formulation in rabbits with acute myocardial infarction (AMI).

Materials and methods: Solubility of radioiodinated hypericin/hypericin (Hyp) in NaCh solutions was evaluated by microscopy. Hyp with ¹²³I-sodium iodide was performed using hydrogen peroxide as oxidant in 0.06?M NaCh. Radiochemical yield determination and purification were conducted using high performance liquid chromatography. ¹²³I-Hyp was solubilized in 0.06?M NaCh containing 1.9?×?10^?4?M Hyp. The formulation was macroscopically inspected and intravenously injected to five rabbits with AMI. At 24?h, biodistribution was evaluated by tissue gamma counting (TGC) and necrosis targetability was assessed by TGC, autoradiography, fluorescence examination and histology.

Results: Microscopically NaCh at 0.06?M shows the best properties for solubilizing the radioiodinated Hyp/Hyp. ¹²³I-Hyp in 0.06?M NaCh was achieved in 85% with radiochemical purity of 99% after purification. NaCh-dissolved ¹²³I-Hyp/Hyp shows no particles. By TGC, animals exhibited higher (p?=?0.003) radioactivity accumulation in AMI (0.8?±?0.2% ID/g) than in normal myocardium (0.05?±?0.02% ID/g), as confirmed by autoradiography, fluorescence measurement and histology. Among organs, the highest uptake of radioactivity was found in liver (15.7?±?0.6% ID), large (9.7?±?1.0% ID) and small (5.9?±?0.6% ID) intestines.

Conclusion: Necrosis avidity of NaCh-dissolved ¹²³I-Hyp/Hyp and its hepatobiliary excretion were demonstrated. The suitability of NaCh as solubilizing agent of ¹²³I-Hyp for hotspot imaging of AMI was proved.     

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.     

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.     

99mTc‐labeled oligomeric nanoparticles as potential agents for folate receptor‐positive tumor targeting

One type of biocompatible nanoparticles functionalized with folate and ^99mTc was successfully synthesized. Maleimide‐folic acid (Mal‐FA) was selected to covalently conjugate with ‐SH of the nanoparticles ( NPs ) to prepare NPs‐FA for targeting. ^99mTc was selected to conjugate with ‐NH₂ and ‐SH groups of cysteine residues on the surface of NPs to prepare NPs‐FA‐ ^99m Tc for radioactive counting. The ability to target folate receptors of NPs‐FA‐ ^99m Tc was assessed in uptake studies with folate‐receptor–positive human HepG2 cells. The results showed that the as‐prepared NPs can selectively uptake by folate receptor‐overexpressing HepG2 tumor cells in vitro. The oligomeric hybrid NPs radiolabeled with ^99mTc may develop to be SPECT/CT imaging biomaterials with high selectivity.     

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.     

Synthesis,Characterization, and Preclinical Evaluation of 99mTc‐Labeled Macrobicyclic and Tricyclic Chelators as Single Photon Emission Computed Tomography Tracer

The novel tetraaza macrobicyclic chelator 3,6,9,15‐tetraazabicyclo[9.3.1]pentadeca‐1(15),11,13‐triene‐2,10‐dione (TBPD) and pentaaza macrotricyclic chelator 9‐oxa‐3,6,12,15,21‐pentaazatricyclo[15,3,2,1]trieicos‐1(21),17,19‐triene‐2,7,11,16‐tetradione (OPTT) were synthesized, characterized, and radiolabeled with ^99mTc to produce ^99mTc‐TBPD and ^99mTc‐OPTT. These radiolabeled complexes were prepared with high radiolabeling yield, radiochemical purity, and good in vitro stability up to 24 h. The labeling efficiency of ^99mTc‐TBPD and ^99mTc‐OPTT was found 98% and 97%. In vitro serum stability of ^99mTc‐TBPD was found to be 95.2%, while that of ^99mTc‐OPTT 94.2% up to 24 h. Blood kinetics experiments of ^99mTc‐labeled complexes showed biphasic pattern of blood clearance. About 99.57 ± 0.89% activity of ^99mTc‐TBPD and 99.42 ± 0.88% activity of ^9mTc‐OPTT were cleared off blood stream at 24 h postadministration. The biological half‐life of ^99mTc‐TBPD was observed: t_1/2(F) 1 h 5 min and t_1/2(S) 12 h and biological half‐life of ^99mTc‐OPTT was observed: t_1/2(F) 1 h 10 min and t_1/2(S) 9 h 50 min, respectively. The biodistribution studies revealed that maximum uptake of ^99mTc‐TBPD was found in liver, concluded that excretory pathway is hepatobiliary, while that of ^99mTc‐OPTT was renal as well as hepatobiliary. The negligible activity observed in stomach confirming the stability of radiolabeled complex in biological milieu. In vitro cytotoxicity study of TBPD and OPTT did not show any considerable antiproliferative activity against cancer cells of human cervical SW756, HeLa, and glioblastoma U‐87, U373 cell lines.     

Synthesis, 99mTc‐labeling,and preliminary biological evaluation of DTPA‐melphalan conjugates

Melphalan (MFL) is a typical nitrogen mustard for the treatment of many types of cancer. For the purpose to develop novel ^99mTc‐labeled tumor imaging agents with SPECT, MFL was directly labeled by ^99mTc using diethylene triamine pentacetate acid (DTPA) as bifunctional chelating agent. The novel ligands were successfully synthesized by conjugation of DTPA to MFL to get monosubstituted DTPA‐MFL and bis‐substituted DTPA‐2MFL. Radiolabeling was performed in high yield to get ^99mTc‐DTPA‐MFL and ^99mTc‐DTPA‐2MFL, respectively, which were hydrophilic and stable at room temperature. The high initial tumor uptake with retention, good tumor/muscle ratios, and satisfactory scintigraphic images suggested the potential of ^99mTc‐DTPA‐MFL and ^99mTc‐DTPA‐2MFL for tumor imaging. However, the slow normal tissue clearance would be a great obstacle. Further modification on the linker and/or ^99mTc‐chelate to improve the tumor targeting efficacy and in vivo kinetic profiles is currently in progress.     

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.     

Preparation,quality control and stability of 99mTc‐sparafloxacin complex,a novel agent for detecting sites of infection

Labeling of sparafloxacin with technetium‐99m using stannous chloride as a reducing agent was investigated. Dependence of the yield of ^99mTc‐sparafloxacin complex on the concentration of sparafloxacin, reducing agent, pH and reaction time was studied. Under optimum conditions, the labeling yield of ^99mTc‐sparafloxacin complex (95%) was achieved by using 2.5 mg of sparafloxacin, 50 µg of Sn(II), pH 10 and 30‐min reaction time. ^99mTc‐sparafloxacin complex was stable for 3 h after labeling, then the yield decreased gradually to 81.9% at 6 h. Biodistribution studies in rats were carried out in experimentally induced infection in the left thigh using Staphylococcus aureus. The ratios of bacterial infected thigh/contralateral thigh were then evaluated. The time for the maximum accumulation of ^99mTc‐sparafloxacin at the site of the infection was 30 min after the administration followed by gradual decline. The abscess‐to‐muscle ratio for ^99mTc‐sparafloxacin was 5.9±0.7, while that for the commercially available ^99mTc‐ciprofloxacin was 3.8±0.5 under the same experimental paradigm, indicating that ^99mTc‐sparafloxacin could be used for infection imaging. Copyright © 2009 John Wiley & Sons, Ltd.     

Evaluation of new positively charged 11‐ and 12‐carbon 99mTc‐labeled fatty acid derivatives for myocardial imaging

Radiolabeled fatty acids are used as tracers for myocardial metabolic imaging and currently ¹²³I‐iodophenyl pentadecanoic acid (IPPA) or ¹²³I‐β‐methyl‐iodophenyl pentadecanoic acid (BMIPP) are the agents of choice. However, ¹²³I being a cyclotron‐produced isotope, ^99mTc‐labeled fatty acids are more desirable substitutes to ¹²³I‐labeled fatty acids. Toward this, two fatty acids, having 11 and 12 carbon atoms respectively, modified with cysteine were synthesized in a four‐step procedure. These ligands were then radiolabeled with ^99mTc using the [^99mTcN(PNP6)]²⁺ core. Formation of the complexes and determination of radiochemical yields were ascertained by HPLC technique. In vivo distribution of the complexes was carried out in Swiss mice and the results are compared with ¹²⁵I‐IPPA. Both the complexes showed fast clearance from the myocardium till 10 min post injection (p.i.) followed by retention in the myocardium till 30 min p.i. However, compared with the result obtained with ¹²⁵I‐IPPA, the amount of activity retained in the myocardium by the present complexes were low. Both the complexes showed rapid clearance from liver, lungs, and blood unlike the case with ¹²⁵I‐IPPA. Copyright © 2010 John Wiley & Sons, Ltd.