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.     

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.     

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 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.     

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.     

Synthesis and evaluation of a novel 99mTc nitrido radiopharmaceutical with alendronate dithiocarbamate as a potential bone‐imaging agent

Currently, a popular strategy for designing novel radioprobes as bone‐imaging agents is based on the concept of bifunctional radiopharmaceuticals. Considering the dithiocarbamate ligand can act as a suitable bifunctional linking agent to attach technetium‐99m (^99mTc) to corresponding target molecules, in this study, alendronate dithiocarbamate (ALNDTC) was synthesized and radiolabeled with [^99mTc≡N]²⁺ core by ligand exchange reaction to produce ^99mTcN‐ALNDTC complex, for the potential use as a novel probe for bone imaging. The radiochemical purity of the complex was over 90%. The complex was stable in vitro and could bind to hydroxyapatite. The partition coefficient result indicated it was hydrophilic, and an evaluation of biodistribution in mice indicated that the complex exhibited a higher bone uptake than did ^99mTc‐labeled methylenediphosphonate (^99mTc‐MDP). Further, single photon emission computed tomography imaging study indicated clear accumulation in bone, suggesting that ^99mTcN‐ALNDTC would be a promising candidate for bone imaging.     

Synthesis and biodistribution of a new (99m) Tc-oxo complex with deoxyglucose dithiocarbamate for tumor imaging

The deoxyglucose dithiocarbamate (DGDTC) was radiolabeled with ^99mTc(V)‐glucoheptonate (GH), for the potential use as radiopharmaceuticals for tumor imaging. For labeling, ^99mTcO‐DGDTC was prepared by ligand‐exchange reaction with ^99mTc‐GH. The radiochemical purity of the ^99mTcO‐DGDTC complex was over 90% by thin‐layer chromatography and high‐performance liquid chromatography, without any notable decomposition at room temperature over a period of 6 h. Its partition coefficient indicated that it was a hydrophilic complex. The ligand‐exchange reaction occured at neutral condition and under 100 °C for 15 min to achieve high radiochemical purity. In vitro cell studies showed there was an increase in the uptake of ^99mTcO‐DGDTC as a function of incubation time and the cellular uptake of ^99mTcO‐DGDTC was possibly mediated by way of a d ‐glucose mechanism. The biodistribution of ^99mTcO‐DGDTC in mice bearing S 180 tumor showed that the complex accumulated in the tumor with good uptake and excellent retention. As compared with other reported ^99mTc radiolabeled glucose derivatives, ^99mTcO‐DGDTC showed the highest tumor uptake and good tumor/muscle ratios. The tumor/muscle ratio of ^99mTcO‐DGDTC uptake was higher than that of [¹⁸F] FDG uptake. Single photon emission computed tomography (SPECT) image studies showed there was a visible accumulation in tumor sites, suggesting ^99mTcO‐DGDTC would be a promising candidate for tumor imaging.     

Synthesis,characterization and biological activity of 99mTc‐labeled piperidine analogues targeting sigma receptors

Sigma receptors are expressed in high density in various types of cancer cells including brain tumours and are also involved in various diseases of central nervous system. This makes ligands that bind to these receptors, attractive molecular vectors for targeting radiation to the specific sites with the purpose of imaging and therapy of neurological disorders. We report synthesis of three derivatives of 4‐amino‐N‐benzylpiperidine namely, 4‐dithiocarbamato‐N‐benzylpiperidine, 4‐iminodiacetato‐N‐benzylpiperidine and 4‐(N‐benzylpiperidine)‐pyridin‐2‐ylmethyl‐amino)‐acetic acid and their radiolabeling with technetium‐99m. The in vivo evaluation of these radiolabeled compounds has been carried out in mice, for assessment of their binding affinity with sigma receptors. Of the three complexes, [^99mTcN]‐4‐dithiocarbamato‐N‐benzylpiperidine, [^99mTcN]Pip‐DTC exhibited the most promising characteristics with brain uptake of 0.6% ID/g at 5 min.p.i. that reduced to 0.3% ID/g after 2 h.p.i. Competition experiment carried out with [^99mTcN]Pip‐DTC complex, using (+)‐pentazocine showed its specificity towards sigma receptors, as was found to be evident from reduction in the brain uptake of this complex. Introduction of iminodiacetate and pyridine moieties and subsequent radiolabeling did not result in complexes with significant potential of targeting and binding with sigma receptors. Copyright © 2010 John Wiley & Sons, Ltd.     

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.     

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.     

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.     

Synthesis,characterization and biodistribution of 99mTc(CO)3–ABP and comparison with 99mTc–ABP

The (l‐hydroxy‐4‐amino‐butylidene‐l,l‐bisphosphate) (ABP) is a compound that inhibits bone resorption, and a highly effective drug in the treatment of metastatic bone disease. The fac‐[^99mTc(CO)₃(H₂O)₃]⁺ precursor was reacted with ABP in saline (pH=3–4) at 45°C for 15 min to produce the ^99mTc(CO)₃–ABP complex. The radiochemical purity (RCP) of the product was over 90% as measured by thin layer chromatography and high‐performance liquid chromatography. No decomposition of the complex at room temperature (25°C) was observed over a period of 6 h. Its partition coefficient indicated that it was a weak hydrophilic complex. The biodistribution in normal mice of ^99mTc(CO)₃–ABP complex differed greatly from that of ^99mTc–ABP, and the former had a lower bone uptake as compared with that of the latter. The experiment results showed that the incorporation of the [^99mTc(CO)₃]⁺ core into the ABP ligand may drastically change the characterization and biological features as compared with ^99mTc–ABP. Copyright © 2007 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.     

Synthesis,quality control,and bio‐evaluation of 99mTc‐cyclophosphamide

Cancer is found to be the leading cause of death worldwide characterized by uncontrolled cell division. Nuclear medicines imaging using radiopharmaceuticals have pronounced potential for the diagnosis and treatment of cancers. Cyclophosphamide (CPH) is an antineoplastic drug which targets selectively cancer cells. In the present work, labeling of CPH with Tc‐99m is performed for diagnostic purpose, which gave labeling yield as high as 99% using 20 μg SnCl₂·2H₂O, 200 μg of ligand at pH 7 for 10 min reaction time at room temperature. The characterization of the prepared complex was performed using ITLC, electrophoresis, and HPLC. In vitro stability was analyzed in the presence of human serum at 37°C which has maximum value of 94 ± 0.5. The biodistribution studies of ^99mTc‐CPH were performed in normal and tumor bearing Swiss Webster mice. The high accumulation of ^99mTc‐CPH was observed in liver and tumours respectively at 4 hr after injection. Biodistribution results revealed that ^99mTc‐CPH may be a potential tumour diagnostic agent simultaneously with chemotherapy.     

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.     

Synthesis and biological evaluation of 99mTc(CO)3(IDA‐CPT) for tumor imaging

This work reports the synthesis, radiolabeling, and preliminary biodistribution results in tumor‐bearing mice of ^99mTc(CO)₃(IDA‐CPT). The novel camptothecin (CPT) derivate was successfully synthesized by conjugation of iminodiacetic acid (IDA) to camptothecin via a short carbonyl‐methylene linker. Radiolabeling was performed in high yield with [^99mTc(CO)₃]⁺ core to get ^99mTc(CO)₃(IDA‐CPT), which was hydrophilic and stable at room temperature. Biodistribution studies in tumor‐bearing mice showed that ^99mTc(CO)₃(IDA‐CPT) accumulated in the tumor with good uptake and retention. However, its clearance from normal organs was slow, resulting in poor T/NT ratios. Further modification on the linker or/and ^99mTc‐chelate to improve the tumor‐targeting efficacy and in vivo kinetic profiles is currently in progress. Copyright © 2009 John Wiley & Sons, Ltd.     

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.     

Preparation and biological evaluation of 99mTc‐stannous fluoride colloid‐labelled‐leucocytes in rats 99mTc‐stannous fluoride‐labelled‐leucocytes in rats

High splenic activity is always visible in ^99mTc‐stannous fluoride (SnF₂)‐labelled‐leucocytes scans. In an attempt to reduce this activity, this study investigated the effect of pre‐injected SnF₂ colloid on the distribution of ^99mTc‐SnF₂ colloid, ^99mTc‐SnF₂‐labelled‐leucocytes, and opsonized ^99mTc‐SnF₂ colloid in rats. The radiopharmaceuticals ^99mTc‐SnF₂ colloid and ^99mTc‐SnF₂‐leucocytes were each found to exhibit identical biodistributions in separate experiments. SnF₂ colloid pre‐injection (26 μg) resulted in reduced splenic uptake of ^99mTc‐SnF₂ colloid (38%) and ^99mTc‐SnF₂‐labelled‐leucocytes (30%), but not for opsonized ^99mTc‐SnF₂ colloid. This indicates that the level of opsonization of radiocolloid is rate limiting rather than the phagocytic capacity of liver and spleen macrophages. There is a low level of ^99mTc‐SnF₂‐labelled‐leucocytes dominated by unopsonized radiocolloid in the ex vivo whole blood dose. Following administration of this dose, free radiocolloid is present in vivo that predominantly localizes in the liver and spleen. This uptake can be challenged with non‐radioactive stannous fluoride colloid pre‐injection, where splenic activity can be significantly reduced by up to 52%. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis and preliminary biological evaluation of a 99mTc‐chlorambucil derivative as a potential tumor imaging agent

Technetium‐99m‐based radiopharmaceuticals have been used widely as diagnostic agents in the nuclear medicine. Chlorambucil (CLB) as one typical alkylating drug exhibits excellent inhibition effects against many human malignancies. To develop and explore a novel potential imaging agent for early diagnosis of tumors, tricarbonyl technetium‐99m and rhenium complexes on the basis of the tridentate ligand dipicolylamine (DPA) bound to the chlorambucil pharmacophore were designed and synthesized: ^99mTc‐DPA‐CLB ( 3 ) and Re‐DPA‐CLB ( 4 ). The high performance liquid chromatography analyses showed that the retention time of 3 and 4 was 13.5 and 13.6 minutes, respectively. Radiolabeling efficiency of the ^99mTc‐DPA‐CLB tracer was 97%, and the radiochemical purity was larger than 95% after 6 hours stored in phosphate buffered saline or human serum as observed by thin layer chromatography and high performance liquid chromatography. Biodistribution studies in a mouse model of breast cancer showed ^99mTc‐DPA‐CLB exhibited a favorable tumor affinity. The radiotracer cleared quickly in the first hour via hepatobiliary and renal routes of excretion, resulted in a very low background at 4 hours post injection (p.i.). It had moderate uptake ratios of tumor to blood and tumor to muscle. These results suggested ^99mTc‐DPA‐CLB might be a promising SPECT imaging agent for tumor diagnosis.     

99mTc‐tricabonyl labeling of ofloxacin and its biological evaluation in Staphylococcus aureus as an infection imaging agent

Even in recent decades, one of the major causes of death and unhealthiness in the whole world is infection and inflammation. The use of radiopharmaceuticals is a powerful tool in managing the patients with infectious diseases. In this study, ofloxacin as a second‐generation fluoroquinolone has been labeled with [^99mTc(CO)₃(H₂O)₃]⁺ core to formulate a suitable infection imaging agent. Ofloxacin was radiolabeled with ^99mTc using carbonyl core. Radioligand chemical analysis involved HPLC methods. Radioconjugate stability and lipophilicity were determined. Binding with Staphylococcus aureus and biodistribution in infected mice for labeled compound were studied. The radioligand was characterized by HPLC, and its radiochemical purity was more than 90%. In vitro stability studies have shown the complex was stable at least 6 h after labeling at room temperature. The n‐octanol/water partition coefficient experiment exhibited logP = 1.52 ± 0.21 for ^99mTc(CO)₃‐ofloxacin. The complex showed specific binding to S. aureus. Biodistribution results showed that radioligand had high accumulation in the infected muscle in a mice (T/NT = 2.02 ± 0.12 at 4 h postinjection). On the basis of stability and infection site uptake ratio, suitability of this complex as a radiotracer for imaging of infections is recognized.