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.     

Synthesis and bio evaluation of a new fatty acid derivative labelled with technetium‐99m

¹²³I‐iodophenylpentadecanoic acid (IPPA) and ¹²³I‐beta‐methyliodophenylpentadecanoic acid (BMIPP) are radiolabelled fatty acid derivatives used for assessment of myocardial viability. Because of limited accessibility of ¹²³I in the clinical scenario, a 99m‐technetium‐based agent would be more advantageous. In this context, a xanthate derivative of 15‐hydroxypentadecanoic acid (HPDA) was synthesized for radiolabelling with [^99mTcN]²⁺ intermediate. Direct reaction of the HPDA with carbon disulphide in presence of crushed sodium hydroxide in dry tetrahydrofuran resulted in moderate yield of the desired xanthate product. The prepared ligand was radiolabelled with [^99mTcN]²⁺ intermediate and the resultant complex was characterized by paper electrophoresis and HPLC. The labelled preparation was assessed for its myocardial extraction and retention characteristics using Swiss mice model. The HPDA xanthate derivative was obtained in a low yield of ～30%. Labelling via the [^99mTcN]²⁺intermediate gave more than 95% complexation. During in vivo studies with the [TcN]²⁺ labelled complex maximum heart uptake observed was 3.10%ID/g at 5 min p.i., which cleared out rapidly, with retention of 0.79%ID/g of the activity at 60 min p.i. The ^99mTcN‐HPDA xanthate derivative showed some uptake in the heart but rapid wash out and substantial uptake in the background organs (blood, liver and lungs) led to unfavourable critical ratios at all the time points of study. Copyright © 2006 John Wiley & Sons, Ltd.     

Synthesis and biodistribution in mice of a new 99mTc nitrido complex for brain imaging

The bis(N‐cyclopentyl dithiocarbamato) nitrido technetium‐99m complex ^99mTcN(CPEDTC)₂ was synthesized by the reduction of ^99mTcO into [^99mTc≡N]²⁺ with stannous chloride in the presence of succinic dihydrazide and propylenediamine tetraacetic acid, followed by the addition of sodium N‐cyclopentyl dithiocarbamate monohydrate. The radiochemical purity (RCP) of the product was over 90% as measured by thin layer chromatography(TLC) and high performance liquid chromatography(HPLC). In vitro studies showed that the complex possessed good stability under physiological conditions. Its partition coefficient studies indicated it was a good lipophilic complex. The electrophoresis results showed the complex was neutral. The biodistribution results in mice indicated that ^99mTcN(CPEDTC)₂ was significantly retained into the brain. The brain uptake(ID%/g) was 3.58, 5.26, 3.73 and 2.72 and the brain/blood ratios were 0.79, 1.69, 1.59 and 1.58 at 5, 30, 60 and 90 min post‐injection, respectively. These results suggested potential usefulness of the complex as a new brain perfusion imaging agent. Copyright © 2004 John Wiley & Sons, Ltd.     

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 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,characterization and biodistribution of a new technetium‐99 m nitrido complex with 2‐methoxyisobutylisonitrile and comparison with 99mTc–MIBI

The preparation of complex ^99mTcN–MIBI was carried out using two alternative procedures that led to the formation of the complex with high radiochemical purity (>90%). The partition coefficient, electrophoresis and cationic resin exchange experiments showed that the ^99mTcN–MIBI is a lipophilic and neutral complex, the structure of this complex is six‐coordinate distorted octahedral, its composition may be [^99mTcNCl₂(MIBI)₃], and the optimized geometry of this complex was calculated by using Gaussian 98 for Window (G98W) program. The biodistribution of ^99mTcN–MIBI shows high myocardial uptake and good target/non‐target ratios in mice at early post‐injection time, for 5 min post‐injection the heart‐to‐blood, heart‐to‐lungs and heart‐to‐liver ratios are 3.18, 1.72 and 1.42, respectively. In respect of the relatively good rations after 5 min and the rapid clearance from non‐target, the complex ^99mTcN–MIBI may be suitable for instant myocardial imaging. In addition, the lyophilized kit enables the convenient preparation of this complex for clinical use. Based on these promising properties, ^99mTcN–MIBI should be a new potential myocardial perfusion‐imaging agent. Copyright © 2002 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.     

Development of kit formulations for 99mTcN‐MPO: a cationic radiotracer for myocardial perfusion imaging

The objective of this study was to develop a kit formulation for [^99mTcN(mpo)(PNP5)]⁺ (MPO = 2‐mercaptopyridine oxide), (^99mTcN‐MPO) to support its clinical evaluations as a SPECT radiotracer. Radiolabeling studies were performed using three different formulations (two‐vial formulation and single‐vial formulations with/without SnCl₂) to explore the factors influencing radiochemical purity (RCP) of ^99mTcN‐MPO. We found that the most important factor affecting the RCP of ^99mTcN‐MPO was the purity of PNP5. ^99mTcN‐MPO was prepared >98% RCP (n = 20) using the two‐vial formulation. For single‐vial formulations with/without SnCl₂, β‐cyclodextrin (β‐CD) is particularly useful as a stabilizer for PNP5. The RCP of ^99mTcN‐MPO was 95–98% using β‐CD, but its RCP was only 90–93% with γ‐cyclodextrin (γ‐CD). It seems that PNP5 fits better into the inner cavity of β‐CD, which forms more stable inclusion complex than γ‐CD in the single‐vial formulations. The results from biodistribution and imaging studies in Sprague–Dawley rats clearly demonstrated biological equivalence of three different formulations. Single photon‐emission computed tomography data suggested that high quality images could be obtained at 0–30‐min post‐injection without significant interference from the liver radioactivity. Considering the ease for ^99mTc‐labeling and high RCP of ^99mTcN‐MPO, the non‐SnCl₂ single‐vial formulation is an attractive choice for future clinical studies.     

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.     

Initial evaluation of 99mTc‐tricarbonyl‐cyclopentadienyl fatty acids derivatives as SPECT tracers for myocardium

Fatty acids are myocardial metabolic agent for detecting myocardial ischemia and infraction. However, no ^99mTc‐labeled fatty acids had potential use in clinical practice. In this study, ^99mTc‐CpTT‐10‐oxo‐para‐PPA ( 1d ), ^99mTc‐CpTT‐11‐oxo‐para‐PPA ( 2d ), ^99mTc‐CpTT‐12‐oxo‐para‐PPA ( 3d ), ^99mTc‐CpTT‐11‐oxo‐ortho‐PPA ( 4d ), and ^99mTc‐CpTT‐11‐oxo‐meta‐PPA ( 5d ) were synthesized by a double ligand transfer reaction, and their biological behaviors were investigated. Compound 2d achieved good heart to blood ratio (3.39 at 5 min after intravenous), and 2d showed high‐heart uptake of 6.20% ID/g at 5 minutes after injection. Compound 3d displayed a prolonged retention in the myocardium (1.43% ID/g at 60 min after injection). Radioactivity accumulation in the lungs, spleen, and blood was eliminated rapidly. In vivo, metabolite analysis presented that compound 6d may be metabolite of 2d through β‐oxidation in tissue. Unfortunately, the biodistribution studies of 1d , 2d , 3d , 4d , and 5d showed fast heart clearance and poor heart to liver ratios, which suggested that the 5 ^99mTc‐labeled fatty acid analogues cannot be used for diagnosis.     

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.     

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.     

Preliminary studies of a novel cyclopentadienyl tricarbonyl technetium‐99m fatty acid derivative for myocardical imaging

This study reports the synthesis and evaluation studies of 6′‐cyclopentadienyl tricarbonyl technetium‐99m 6′‐oxo‐11‐(hexanamide)undecanoic acid (1). 1 was prepared with 26.5 ± 4.3% of radiochemical yield and more than 98% of radiochemical purity. Tissue distribution in mice showed that high radioactivity accumulated in the heart with moderate clearance. However, unfortunately, similar to those of other technetium‐labeled fatty acid analogs, the biodistribution studies of 1 in mice showed poor heart‐to‐blood ratios, which suggested that 1 cannot be used as myocardial imaging agent, and it may provide a theoretical basis or a lab experience for corresponding fatty acid tracers studies.     

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 and biological evaluation of a novel asymmetrical 99mTc‐nitrido complex of metronidazole derivative

The novel dithiocarbamate derivative of metronidazole, potassium 2‐(2‐methyl‐5‐nitro‐1H‐imidazolyl)‐ethyl‐dithiocarbamate (MNIE‐DTC), was synthesized as the pharmacophore‐containing bifunctional ligand. The corresponding asymmetrical ^99mTc‐nitrido complex, expected as a tumor hypoxia marker, had been successfully obtained by the addition of the biphosphine ligand PNP5 (PNP5 = N‐ethoxethyl‐N,N‐bis[2‐(bis(3‐methoxypropyl)phosphino)ethyl]‐amine) and the dithiocarbamate ligand (MNIE‐DTC) to the ^99mTc‐nitrido precursor solution at 100°C for 15 min. The radiochemical purity of the product was above 95% as measured by thin‐layer chromatography and high‐performance liquid chromatography. In vitro studies showed that the complex possessed good stability under physiological conditions. Its partition coefficient studies indicated that it was a lipophilic complex. The electrophoresis results showed that the complex was cationic. Biological evaluation of the complex [^99mTcN(PNP5)(MNIE‐DTC)]⁺ performed in Kunming mice bearing H22 tumor showed that the complex had a moderate tumor uptake (0.57±0.06%ID/g at 1h), and the ratios of tumor/blood and tumor/muscle were 2.46 and 1.31 at 1h p.i., and reached 4.52 and 2.86 at 4h p.i., respectively. Copyright © 2007 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.     

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,separation and biodistribution of 99mTc‐CO‐MIBI complex

^99mTc‐CO‐MIBI was prepared by a two‐step procedure involving the convenient preparation of the [^99mTc(CO)₃(OH₂)₃]⁺ precursor and followed by the substitution of the water molecules by the MIBI (2‐methoxyisobutylisonitrile) ligands. In a second step, the reaction solution was adjusted to different pH values, and then the product, ^99mTc‐CO‐MIBI, was confirmed to be a mixture of two complexes: complex A and complex B, whose labeling yields could be over 90%. The ratio of complex B to the sum of A and B could increase gradually from 0 to 1 when pH was shifted from 3.0 to 9.0. These changes were monitored by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). The two complexes were stable within 8 h at room temperature in vitro. The partition coefficient of the two complexes indicated that there was distinct difference between them. Biodistribution in mice demonstrated that complex B showed better myocardial imaging properties than that of complex A. The heart/liver ratios of complex A, the mixture, and complex B were 1.57, 1.93, and 2.33, respectively, for 30 min post‐injection. The discovery of chemical and biological properties of ^99mTc‐CO‐MIBI would certainly promote the research on a new promising myocardial perfusion‐imaging agent. Copyright © 2004 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.     

Development of 68Ga‐labeled fatty acids for their potential use in cardiac metabolic imaging

While [¹¹C]palmitate continues to be a promising tracer for cardiovascular Positron Emission Tomography (PET) imaging, unfavourable logistics due to the short half‐life of ¹¹C (20 min) and cumbersome labeling methodologies are the major impediments that limit its widespread use. In order to circumvent such limitations, an attempt has been made to explore the potential of ⁶⁸Ga‐labeled fatty acid analogs for metabolic imaging owing to the availability of ⁶⁸Ga through a ⁶⁸Ge/⁶⁸Ga generator on an on‐demand basis. In this study, two fatty acid conjugates were synthesized by conjugation of p‐SCN‐benzyl NOTA with the ω‐amino group of 11‐amino undecanoic acid and 12‐amino dodecanoic acid, respectively, under alkaline conditions. Both derivatives were radiolabeled in high yields with ⁶⁸Ga obtained from an in‐house ⁶⁸Ge/⁶⁸Ga generator. Biodistribution studies in Swiss mice showed reasonable myocardial uptake at 2 min for both derivatives (7.4 ± 2.8% ID/g for 11‐carbon fatty acid‐NOTA conjugate and 6.4 ± 2.1% ID/g for 12‐carbon fatty acid‐NOTA conjugate), which cleared rapidly over 30 min. However, significant activity was found in blood for both tracers, with heart/blood ratios observed to be below 0.5 at all time points, diminishing the potential of the synthesized complexes for cardiac imaging. Copyright © 2014 John Wiley & Sons, Ltd.