Synthesis of 99mTc(CO)3‐mebrofenin via [99mTc(OH2)3(CO)3]+ precursor and comparative pharmacokinetics studies with 99mTc‐mebrofenin

The organometallic precursor fac‐[^99mTc(OH₂)₃(CO)₃]⁺ was reacted with trimethyl‐bromoacetanilido‐iminodiacetic acid (mebrofenin) in phosphate buffered saline (pH 7) at 70°C for 1 h to produce the complex, ^99mTc(CO)₃‐mebrofenin, in >95% yields. High performance liquid chromatography analysis indicated the formation of a single species. In vitro studies of ^99mTc(CO)₃‐mebrofenin showed that the complex is stable for 24 h. No decomposition or alteration of the complex was observed in the presence of excess amount of cysteine and histidine. ^99mTc‐mebrofenin was also prepared for comparative evaluation by the conventional method using a ready to use kit HPLC analysis of this complex showed presence of two species. Biodistribution studies in normal Swiss mice with ^99mTc(CO)₃‐mebrofenin showed hepatobiliary clearance. However, the retention in liver was higher (13% at 1 h p.i.) as compared to that of ^99mTc‐mebrofenin (3.4% at 1 h p.i.). Copyright © 2003 John Wiley & Sons, Ltd.     

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.     

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.     

Application of 99Mo/99mTc alumina generator in the labeling of metoprolol for diagnostic purposes

Labeling of metoprolol by technetium‐99m in pertechnetate form (^99mTcO) eluted from a ⁹⁹Mo/^99mTc alumina generator in the presence of stannous chloride dihydrate was carried out via chelation reaction. The reaction parameters that affect the labeling yield such as metoprolol concentration, stannous chloride dihydrate concentration, reaction temperature, and pH of the reaction mixture were studied to optimize the labeling conditions. Using 1 GBq ^99mTcO, 500 µg metoprolol as substrate dissolved in 500 µL phosphate buffer at pH 9 and 50 µL of stannous chloride as reducing agent (1 mg/mL) at 25°C for 30 min reaction time, a maximum radiochemical yield of ^99mTc‐metoprolol (92%) was obtained. ^99mTc‐metoprolol was characterized by thin layer chromatography (TLC) and by high pressure liquid chromatography (HPLC). The specific activity of ^99mTc‐metoprolol obtained was 888 MBq/1.88 mmol. The biological distribution in normal mice showed that ^99mTc‐metoprolol is rapidly concentrated after injection in the heart, which indicates its suitability for heart imaging. Copyright © 2009 John Wiley & Sons, Ltd.     

Synthesis,radio‐LC‐MS analysis and biological evaluation of 99mTc‐techmazenil

A ^99mTc‐labelled compound with the biological characteristics of flumazenil would be useful for determination of neuronal viability after the onset of a stroke. Therefore, we have derivatized Ro‐15‐3890 (a flumazenil metabolite bearing a carboxylic acid group instead of an ethyl ester) by coupling it with a bisamino bisthiol tetraligand bearing a 3‐hydroxypropyl side chain (3‐hydroxypropyl‐BAT) to enable labelling with technetium‐99m. After purification by RP‐HPLC, the ligand was deprotected and labelled in a ‘one pot’ reaction, yielding a ^99mTc‐BAT‐propylester of Ro‐15‐3890 (^99mTc‐techmazenil). Radio‐LC‐MS analysis of the isolated main peak showed the molecular ion mass (608.0618) of the expected ^99mTc‐techmazenil. The biodistribution of ^99mTc‐techmazenil was investigated in normal mice and indicated that the tracer is cleared from plasma mainly by the hepatobiliary system and shows a very low uptake in brain. In vitro binding studies on mice brain slices indicated that techmazenil does not bind to benzodiazepine receptors. Copyright © 2004 John Wiley & Sons, Ltd.     

Preparation via coligand exchange and characterization of [99mTc‐EDDA‐HYNIC‐D‐Phe1,Tyr3]Octreotide (99mTc–EDDA/HYNIC–TOC)

[^99mTc‐EDDA–HYNIC‐D‐Phe¹,Tyr³]octreotide (^99mTc‐EDDA/HYNIC–TOC) is a promising new agent with the potential to replace [¹¹¹In‐DTPA‐D‐Phe¹]‐octreotide in somatostatin receptor scintigraphy. This hydrazinonicotinic acid derivatized somatostatin complex contains ethylenediamine N,N′ diacetic acid (EDDA) as a coligand resulting in a high in vitro and in vivo stability. Since direct ^99mTc‐labelling of HYNIC–TOC with EDDA results in low labelling yields, in this study we describe the preparation of ^99mTc‐EDDA/HYNIC‐TOC via coligand exchange from Tricine for EDDA. Exchange of coligands is achieved at elevated temperature and under optimized conditions of pH, EDDA concentration and stannous ion. High labelling yields (mean 95.9%) were achieved at high specific activities (>37GBq/µmol). Characterization via HPLC, receptor binding and LC–MS of the resulting complex is described. The formulation developed enables rapid and simple labelling of ^99mTc‐EDDA/HYNIC–TOC in a manner suitable for a clinical setting. Copyright © 2003 John Wiley & Sons, Ltd.     

Development of 99mTc‐thioflavin‐T derivatives for detection of systemic amyloidosis

In a search for a ^99mTc‐labelled tracer agent for imaging of amyloid plaques in patients with systemic amyloidosis (SA), we have conjugated three bifunctional chelating ligands, namely S‐benzyl‐mercaptoacetyl‐l‐aspartyl(tBu)‐glycine, HYdrazinoNICotinic acid and nitrilotriacetic acid, to the 2‐phenylbenzothiazole core of thioflavin‐T (ThT), which has known affinity for amyloid. The compounds were successfully synthesized and labelled with technetium‐99m. Their structure was confirmed by radio‐LC‐MS analysis. After i.v. injection in normal mice, all three ^99mTc‐labelled ThT derivatives were excreted almost exclusively via liver and intestines. This indicates that the new tracer agents have not the required biokinetics for application as a probe for detection of SA in the abdominal region. Copyright © 2008 John Wiley & Sons, Ltd.     

Physico‐chemical characterisation of 99mTc‐tin fluoride colloid agent used for labelling white cells

^99mTc–tin fluoride colloid is an agent used to label leucocytes, for the imaging and diagnosis of inflammatory conditions including Crohn's disease. Despite previous investigations, this radiolabelling agent is still poorly characterised. The aim of this work was to examine the process of formation and stability of ^99mTc–tin fluoride colloid using mass spectrometry, membrane filtration and atomic absorption spectrophotometric techniques. Tin‐oxide bonds in tin clusters were identified in the stannous fluoride reagent vial by mass spectrometry. From radioactive particle size distribution experiments, the facile disruption of radiocolloid particles with excess oxygen gas contrasted to the partial hydrolysis of Sn(II) during the formation process. Under the standard conditions, 10% of particles were determined as 1–3 µm, and this population coordinated 96% of the ^99mTc added. Colloid particle formation and the reduction of ^99mTc‐pertechnetate is discussed. Sodium fluoride may optimise 1–3 µm radioactive particle size, by regulating particle growth. ^99mTc–tin fluoride colloid is affected by positive or negative charge, as either Al, Mo ions or solid membranes, resulting in either coagulation and/or deflocculation of the particles. Copyright © 2006 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.     

Biodistribution of 99mTc‐sunitinib as a potential radiotracer for tumor hypoxia imaging

Tyrosine kinases are groups of enzymes, which are over‐expressed in solid tumor cells, representing good targets for different drugs such as sunitinib (N‐[2‐(diethylamino)ethyl]‐5‐{[(3Z)‐5‐fluoro‐2‐oxo‐2,3‐dihydro‐1H‐indol‐3‐ylidene]methyl}‐2,4‐dimethyl‐1H‐pyrrole‐3‐carboxamide). The aim of this work was to design and synthesize ^99mTc‐sunitinib radiotracer and to study its tumor binding specificity as a novel selective radiopharmaceutical for tumor hypoxia imaging. The in vivo biodistribution of ^99mTc‐sunitinib in tumor bearing mice showed high target/non‐target (T/NT) ratio (T/NT ~ 3 at 60 min post injection). This preclinical high biological accumulation in tumor cells suggests that ^99mTc‐sunitinib is ready to go through the clinical trials as a potential selective radiotracer able to image tumor hypoxia.     

99mTc‐Doxycycline hyclate: a new radiolabeled antibiotic for bacterial infection imaging

Radiolabeled antibiotics are promising radiopharmaceuticals for the precise diagnosis and detection of infectious lesions. Doxycycline Hyclate (DOX) was chosen to investigate new ^99mTc‐labeled antibacterial agent. Ready to use freeze dry kits were formulated with optimum labeling conditions. Human serum stability, sterility, and pyrogenicity of kits were estimated, and gamma scintigraphy, in vivo biodistribution, and histopathological studies with bacterial infected rats were performed. DOX were successfully labeled by ^99mTc with high radiochemical purity, and the labeled compound was stable in human serum. Kits were sterile, pyrogen‐free, and stable up to 6 months. Static images depicted rapid distribution throughout the body and high uptake in bacterial infected thigh muscle. The uptake ratios of radiopharmaceuticals in infected thigh muscle were found above 2 up to 5 h. Five hours after injection, the rats were sacrificed, and biodistribution was determined. Samples of bacterial infected muscle, healthy muscle, blood, liver, spleen, lung, kidney, stomach, intestine, urine and heart were weighed, and the radioactivity was measured by using a gamma counter. The %ID/g of ^99mTc‐DOX was found 0.23 ± 0.06 for infected thigh muscle. According to the imaging, biodistribution, and histopathological studies, the promising characteristics of ^99mTc‐DOX make the new radiopharmaceutical valuable to examine for future studies. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis and preclinical pharmacological evaluation of 99mTc‐TEDP as a novel bone imaging agent

The detection of bone metastasis in early stages requires the development of high‐affinity bone imaging radiopharmaceuticals for the improvement of the diagnostic accuracy of routine bone scanning and effective management of these medical cases. This study aimed to provide a convenient synthesis of 1‐thioethylidene‐l,l‐disodiumphosphonate (TEDP) and an improved preparation of its ^99mTc‐TEDP complex. The results showed that the radiochemical purity of ^99mTc‐TEDP was found to be 95 ± 2% and that its stability was up to 6 h. Biodistribution study showed high and long uptake of ^99mTc‐TEDP in bone starting from 15 min (39 ± 4 ID/g) to 3 h (53 ± 2.4 ID/g) showing high affinity of ^99mTc‐TEDP complex to bones. This research could introduce a novel radiopharmaceutical that could be used in scanning body bones starting from 15 min between injection of ^99mTc‐TEDP and bone imaging, minimizing the burden on patients in terms of the total length of the examination and the dose of radiation absorbed and showing high specificity and efficacy in bone scintigraphy.     

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.     

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.     

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.     

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.     

Synthesis,radio‐LC–MS analysis and biodistribution in mice of 99mTc–NIM–BAT

S,S′‐bis‐trityl‐N‐BOC‐1,2‐ethylenedicysteamine (S,S′‐bis‐trityl‐N‐BOC–BAT) was conjugated to 2‐nitroimidazole (NIM) through a propylene spacer in order to provide a precursor for a potential technetium‐99 m labelled hypoxia tracer. For labelling with technetium‐99 m, a two‐step one‐pot procedure was developed consisting of deprotection of the ligand by heating in mild acidic conditions and subsequent exchange labelling in the presence of SnCl₂, tartrate and ^99mTcO. The labelling reaction mixture was analyzed using electrospray radio‐LC–MS and the observed mass spectrum corresponding to the main radiometric peak was in accordance with the predicted structure of oxo–Tc(V)–NIM–BAT. ^99mTc–NIM–BAT was purified using RP–HPLC and its biodistribution was evaluated in normal mice at 10 min and 4 h p.i. ^99mTc–NIM–BAT was cleared from plasma mainly by hepatobiliary excretion. Copyright © 2003 John Wiley & Sons, Ltd.     

A 99mTc(CO)3‐labeled benzylguanidine with persistent heart uptake

We describe the synthesis and biological evaluation of the cationic ^99mTc–tricarbonyl complex fac‐[^99mTc(CO)₃(κ³‐L1)]⁺ (Tc1) anchored by a pyrazole‐diamine‐methylbenzylguanidine‐based ligand (L1), as potentially useful for myocardial imaging. The rhenium complex fac‐[Re(CO)₃(κ³‐L1)]⁺ (Re1) was prepared and characterized as a ‘cold’ surrogate of the radioactive complex. Cell uptake studies in a neuroblastoma cell line suggest that Tc1 uptake mechanism is related to the norepinephrine transporter (NET). Tissue distribution studies in CD1 mice showed that Tc1 presents high initial heart uptake and a slow washout from the heart (7.8 ± 1.3% injected dose per gram (ID/g), 30‐min post‐injection (p.i.); 6.3 ± 1.3% ID/g, 60‐min p.i.), with heart to blood ratios of 11.8 and 9.0 at 30‐ and 60‐min p.i., respectively. The uptake mechanism of Tc1 appears to be similar to that of metaiodobenzylguanidine (MIBG), as it can be reduced by coinjection with nonradioactive MIBG. The biodistribution profile of Tc2, where the benzylguanidine pharmacophore is absent, corroborates the fact that Tc1 does not accumulate in the heart by a simple diffusion mechanism but rather by a NET‐mediated mechanism. The results confirm those obtained in the cell assays. Despite the persistent heart uptake found for Tc1, the high hepatic and renal uptake remains to be improved.     

Technetium‐99m labeling and freeze‐dried kit formulation of levofloxacin (L‐Flox): a novel agent for detecting sites of infection

In this study, the labeling method of levofloxacin with technetium‐99m and its biological evaluation were described. ^99mTc‐L‐Flox was synthesized via direct complexation with technetium‐99m in the presence of stannous chloride dihydrate as reducing agent. The optimum amounts of the reactants are: 1–2 mg levofloxacin, 150 µg stannous chloride dihydrate and 48–1490 MBq pertechnetate. The reaction mixture was bring to pH 6 and kept at room temperature for 30 min. The labeled levofloxacin was stable for more than 8 h. The in vivo evaluation of ^99mTc‐L‐Flox in man‐induced inflammation models showed that this tracer was localized with different values. The live E. Coli model had the highest value which was 2.9%, the heat killed E. coli model had a value of 2.0%, and the turpentine oil model had a value of 1.2% at 24 post injection, while the non‐inflamed muscle had activity of 0.5%. All the gathered biological data support the usefulness of ^99mTc‐L‐Flox as infection imaging agent. The freeze‐dried form of Sn‐L‐Flox was prepared and found meet all the radiochemical and biological tests. Copyright © 2007 John Wiley & Sons, Ltd.     

Preparation and biological evaluation of 99mTc–ropinirole as a novel radiopharmaceutical for brain imaging

Noninvasive brain imaging is a process that allows scientists and physicians to view and monitor the areas of the brain. The aim of this study was to formulate a novel radiopharmaceutical for the detection of brain disorders at early stages in susceptible patients. ^99mTc–ropinirole was prepared by the direct complexation of ropinirole with technetium‐99m. The results showed that the radiochemical yield ^99mTc–ropinirole was 92 ± 2.87% and the radiochemical yield was evaluated by paper chromatography and HPLC. In vitro studies showed that the formed complex was stable for up to 6 h. In vivo uptake of ^99mTc–ropinirole in the brain was 4.87 ± 0.15% injected dose/g organ at 30 min post‐injection, which cleared from the brain with time till it reaches 2.3% at 2 h post‐injection indicating that the brain uptake of ^99mTc–ropinirole is higher than that of the commercially available ^99mTc‐HMPAO, which is 2.25% at 30 min. Pre‐dosing mice with cold ropinirole reduced the brain uptake to 0.26 ± 0.01% injected dose/g organ, so this confirms the high specificity and selectivity of this radiotracer for the assessment of the dopamine receptors.