Radioiodinated acebutolol as a new highly selective radiotracer for myocardial perfusion imaging

Acebutolol was successfully labeled with ¹²⁵I via direct electrophilic substitution reaction. Radioiodinated acebutolol was prepared with a maximum radiochemical yield of 96.5 ± 0.3% and in vitro stability up to 72 h. The in vivo biological distribution of radioiodinated acebutolol showed high heart uptake of 37.8 ± 0.14% injected activity/g organ with low lungs and liver uptakes at 5 min post‐injection. In vivo receptor blocking study was carried out in mice to evaluate its selectivity to heart. Radioiodinated acebutolol showed fast heart accumulation with high heart/liver ratio, which provides the ability for fast myocardial imaging with significant decrease in the radiation hazards risk on patients. So, radioiodinated acebutolol could be displayed as a radiotracer drug of choice in case of emergency patients for myocardial perfusion imaging.     

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 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,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.     

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.     

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 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.     

Preparation and biodistribution of novel 99mTc(CO)3‐CNR complexes for myocardial imaging

We evaluated lipophilicity and biodistribution of a series of ^99mTc(CO)₃‐ether isonitrile complexes to determine whether different lipophilicity and structure of isonitrile ligands would improve the imaging properties of the radiopharmaceutical for the heart. Novel ^99mTc(CO)₃‐MIBI analogs were prepared and analyzed by radio‐HPLC, and their lipophilicity was determined. These new complexes could be bi‐ or tri‐substituted in specified pH conditions like ^99mTc(CO)₃‐MIBI. These new complexes exhibited low liver, lungs and blood uptake compared with [^99mTc(CO)₃(MIBI)₃]⁺ though their heart uptake was not so high. Among these complexes, [^99mTc(CO)₃(EPI)₂(OH₂)]⁺ showed higher target to non‐target ratios at 5 and 30 min post‐injection than that of [^99mTc(CO)₃(MIBI)₃]⁺. Copyright © 2007 John Wiley & Sons, Ltd.     

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.     

核素心肌灌注显像在无症状心肌梗死诊断中的应用

目的：探讨应用核素心肌灌注显像（NMPI）诊断无症状心肌梗死（MI）的临床价值。方法动态心电图或其他心电检测技术检测的无症状M I患者30例,均行NM PI和冠状动脉造影检查,计算NM PI显像阳性结果预测值。结果30例NM PI中,12例表现为不可逆性心肌缺血,18例表现为混合性心肌缺血。冠状动脉造影检出阳性血管45支（血管狭窄≥50％）,其中的28支狭窄＞90％,15支70％＜狭窄≤90％,2支狭窄≤70％。NMPI阳性结果预测值为88.9％。结论 NMPI对诊断无症状MI和评估心肌损害程度有重要价值。     

Preparation and biological evaluation of 99mTcN‐4‐(cyclohexylpiperazin‐1‐yl)‐dithioformate as a potential sigma receptor imaging agent

The goal of this study is to develop a novel ^99mTc‐labeled σ receptor imaging agent. Potassium 4‐(cyclohexylpiperazin‐1‐yl)‐dithioformate, 2 , and the corresponding rhenium complex, ReN‐2 , were synthesized and characterized. ReN‐2 possessed moderate affinity toward σ₁ (K_i = 1.94 ± 0.60 µmol/L) and σ₂ (K_i = 2.83 ± 1.39 µmol/L) receptors. The radiolabeled complex ^99m TcN‐2 was prepared in high yield (> 95%) through the [^99mTcN] precursor and characterized by HPLC. ^99m TcN‐2 was found to be a lipophilic and neutral complex with good stability. The biodistribution in tumor‐bearing mice showed that ^99m TcN‐2 had good tumor uptake (2.12 ± 0.01 %ID/g at 2 h p.i.) and moderate brain uptake (0.27 ± 0.05 %ID/g at 2 h p.i.). After blocking with haloperidol, the uptakes by tumor and brain were lower than control. The results indicated that the complex has specific binding to the σ receptors in vivo. Further structural modifications of this complex are needed to obtain ^99mTc‐based σ receptor imaging agents with high affinity and subtype selectivity. Copyright © 2007 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.     

N‐[3‐[4‐(2‐methoxyphenyl) piperaziny‐1‐yl]propyl]cyclam: synthesized as a potential 5‐HT1A receptor ligand and labelled with 99mTc‐nitrido core

This paper reports the synthesis of new potential 5‐HT_1A receptor ligand N‐[3‐[4‐(2‐methoxyphenyl)piperaziny‐1‐yl]propyl]cyclam (MPPC) and radiolabelling of it with ^99mTc‐nitrido core. The novel neutral complex ^99mTcN‐MPPC combines 1,4,8,11‐tetraazacyclotetradecane (cyclam) ligand as chelate moiety for ^99mTc‐nitrido with a 1‐(2‐methoxyphenyl)piperazine moiety derived from WAY 100635 via a 3‐carbon alkyl chain. This provided a reliable and reproducible method for attaching the technetium to the pharmacophore moiety of WAY 100635. ^99mTcN‐MPPC was prepared by a two‐step procedure and the radiochemical purity was found to be greater than 95%. It was hydrophilic and stable for at least 4 h at room temperature. In vivo stability study in normal rats showed that no degradation of ^99mTcN‐MPPC was found in deproteinated blood samples at 2 h post‐injection. This effective ^99mTc‐labelling strategy for obtaining neutral ^99mTc nitrido complexes would be a useful tool to prepare new SPECT agents to image 5‐HT_1A receptor with cyclam conjugated ligands. Copyright © 2008 John Wiley & Sons, Ltd.     

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.     

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.     

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

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

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.     

核素心肌灌注显像在左心衰竭与心肌缺血相关性研究中的临床价值

目的利用核素心肌灌注显像,分析左心衰竭与心肌缺血之间的相关性,为临床心力衰竭治疗决策提供重要依据。方法选取临床确诊的各类左心衰竭住院患者75例,其中男性46例,女性29例,年龄35～85岁,平均(60±24)岁,行核素心肌灌注显像,对其中阳性显像追加冠状动脉造影检查。将患者分为心肌灌注显像阴性组和心肌灌注显像阳性组,分别对负荷和静息2次左心室收缩末期容积、舒张末期容积进行行×列表χ2检验,观察缺血面积与心室容量整体的相互差异。同时对其中符合临床支架植入指征的30例患者进行了冠状动脉支架植入术,术后21例复查了核素心肌灌注显像并与术前进行了对比分析。结果核素心肌灌注显像结果无明显异常者15例,轻度缺血15例,中度缺血36例,且均为负荷显像阳性,静息显像阴性的可逆性缺血;严重缺血9例,均为负荷、静息显像阳性的不可逆性缺血。缺血面积百分比为(15±10)%,严重程度标准差值平均为-2.7±1.8,射血分数(EF)值为(43±8)%。不同缺血范围水平级的左心室容积和缺血范围,按α=0.05检验水准,呈现缺血越严重,心室容积越大趋势,心室射血功能也相应下降。缺血面积与负荷舒张末期容积、静息舒张末期容积、负荷收缩未期容积、静息收缩末期容积的相关系数(r值)分别为0.68、0.70、0.65、0.73,P值均<0.01。60例核素心肌灌注显像阳性组患者行冠状动脉造影检查,结果为46例有不同程度狭窄(≥50%)。21例支架植入术后患者左心室容量恢复具有统计学意义(P<0.05)。结论核素心肌灌注显像为临床早期判断左心衰竭病因,从而做出及时正确的决策有着重要临床意义。     

Development of a single vial kit formulation of [99mTc]‐labeled doxorubicin for tumor imaging and treatment response assessment‐preclinical evaluation and preliminary human results

The present study describes the successful radiolabeling of [99mTcO^?₄] with doxorubicin, and the resultant product was formulated in to a ready‐to‐label lyophilized single vial kit preparation for convenient use in a routine clinical setting. The radiolabeled preparation of [99mTc]‐doxorubicin exhibited a high radiolabeling efficiency of more than 95.0%, serum stability for up to 24 h, and shelf‐life of lyophilized cold kits was more than 6 months. Animal imaging data in tumor‐bearing mice demonstrated that [99mTc]‐doxorubicin accumulated in the tumor site with high target (tumor) to non‐target (contra‐lateral thigh) ratio (3.2 ± 0.5). The ratio decreased to 1.2 ± 0.6 indicating a good response on follow up imaging performed after 2 weeks of doxorubicin treatment. [99mTc]‐doxorubicin scintigraphic data in human volunteers supported the hepato‐renal excretion of the radiotracer as reflected by the increased accumulation of the radiotracer as a function of time in intestine, kidneys, and urinary bladder. Further, imaging in patients (very limited number) indicated that the technique may be useful in the detection of active sarcoma and post treatment (surgery/chemotherapy) remission or absence of the disease. The technique, however, needs validation through further preclinical evaluation and imaging in a larger number of patients.     

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.