Labeling,biodistribution and evaluation of [125I] gemcitabine: a potential agent for tumor diagnosis and radiotherapy

In this study, the optimization of gemcitabine labeling with iodine‐125 and its biological evaluation are described. Gemcitabine was labeled via direct electrophilic substitution using chloramine‐T as an oxidizing agent. The optimum amounts of reactants were 75 µg gemcitabine, 75 µg chloramine‐T and 18 MBq carrier‐free Na¹²⁵I. The labeled gemcitabine was stable for more than 20 h. Results of the in vivo evaluation revealed that the new tracer, [¹²⁵I] gemcitabine, tends to localize in tissues with high proliferation rate with preferential accumulation in cancerous tissues. Imaging should be carried at 2‐h postinjection. The in vitro cell growth inhibition assay showed that the effect of [¹²⁵I] gemcitabine was stronger than the effect of tenfold cold gemcitabine, which strongly suggested that its cytotoxicity was mainly due to radiotoxicity rather than chemotherapeutic activity. The binding assay revealed that [¹²⁵I] gemcitabine uptake by the Ehrlich cells was high and that it bound well to DNA where the decay of the radionuclide introduced lethal irreversible double‐strand breaks. Copyright © 2009 John Wiley & Sons, Ltd.     

Preparation and evaluation of [125I]troxacitabine: L‐nucleoside model of a potential agent for tumor diagnosis and radiotherapy

In this study, the optimization of troxacitabine labeling with iodine‐125 and its biological evaluation were described. Troxacitabine was labeled via direct electrophilic substitution using chloramine‐T as oxidizing agent. The optimum amounts of reactants were: 50 µ g troxacitabine, 75 µ g Chloramine‐T and ～19 kBq carrier free Na¹²⁵I. The labeled troxacitabine was stable for more than 24 h. Results of the in‐vivo evaluation revealed that the new tracer, [¹²⁵I]troxacitabine, tends to localize in tissues with high proliferation rate with preferential accumulation in cancerous tissues. Imaging should be carried at 3 h postinjection. The in vitro cell growth inhibition assay showed that the effect of [¹²⁵I]troxacitabine was stronger than the effect of cold troxacitabine, which strongly suggested that its cytotoxicity was mainly due to radiotoxicity rather than chemotherapeutic activity. The binding assay revealed that [¹²⁵I]troxacitabine uptake by the Ehrlich and the ARAC8C cells was high and that it bounded well to DNA. Copyright © 2010 John Wiley & Sons, Ltd.     

Iodine‐125‐terbutaline (125ITB): a new β2‐adrenoceptor probe for lung imaging

Development of a selective β₂‐adrenoceptor tracer for single photon emission tomography is important for imaging of the lungs. Iodine‐125‐terbutaline (¹²⁵ITB) was prepared by the reaction of terbutaline with iodine‐125 in the presence of chloramine‐T as the oxidizing agent. The reaction was completed by incubation of the reaction mixture at 70°C for 15 minutes at pH 7. The biodistribution study in mice indicated the ability of the tracer to bind β‐adrenoceptors in lungs, liver, heart, and spleen. The localization of the tracer in the lungs was high (85%/g at 60 minutes post‐injection) and the highest lung/blood/g ratio was 19.8% at 60 minutes post‐injection. The selectivity of the tracer for the β₂‐adrenoceptor was examined by blocking with both β₁ and β₂‐adrenoceptor selective antagonists. The results showed reduction of both heart and lung uptake of the ¹²⁵ITB tracer, indicating a moderate (not absolute) selectivity for the β₂‐adrenoceptor. Copyright © 2012 John Wiley & Sons, Ltd.     

18F labeled RGD‐A7R peptide for dual integrin and VEGF‐targeted tumor imaging in mice bearing U87MG tumors

The aim of this study is to develop a novel Arg‐Gly‐Asp acid (RGD) and Ala‐Thr‐Trp‐Leu‐Pro‐Pro‐Arg (ATWLPPR A7R) peptide‐containing ligand for ¹⁸F labeling as αvβ3 and vascular endothelial growth factor receptor‐targeted imaging agent. ¹⁸F‐RGD‐A7R was prepared by conjugation with ¹⁸F‐SFB. The final product was purified by high‐performance liquid chromatography and tested in vitro and in vivo. Cell‐binding assays of RGD‐A7R, RGD and RGD‐A7R, A7R were tested in U87MG cells (¹²⁵I‐RGDyK and ¹²⁵I‐A7RY as radioligand, respectively). Preliminary biodistribution of the ¹⁸F‐RGD‐A7R was also evaluated. The RGD‐A7R had good integrin binding affinity (50% inhibitory concentration (IC₅₀) = 21.67 and 23.68 nM, slightly lower than unmodified RGD (40.02 nM) and A7R (50.18 nM)). The radiotracer had receptor‐mediated activity accumulation in U87MG tumor (1.90 ± 0.34 percentage of injected dose per gram (%ID/g) at 0.5 h postinjection), which is known to be integrin positive. After blocking with RGD‐A7R, the tumor uptake was reduced to 0.47 ± 0.06 %ID/g at 0.5 h postinjection. ¹⁸F‐RGD‐A7R exhibited dual receptor targeting properties both in vitro and in vivo. The favorable characterizations of ¹⁸F‐RGD‐A7RY, such as convenient synthesis, high specific activity, and high tumor uptake, warrant its further investigation for clinical cancer imaging.     

Synthesis and biological evaluation of 125I/123I‐labelled analogues of citalopram and escitalopram as potential radioligands for imaging of the serotonin transporter

Two novel radioligands for the serotonin transporter (SERT), [¹²⁵I]{3‐[5‐iodo‐1‐[4‐fluorophenyl)‐1,3‐dihydroisobenzofuran‐1‐yl]‐propyl}‐dimethylamine ([¹²⁵I]‐2) and S‐[¹²⁵I]{3‐[5‐iodo‐1‐(4‐fluorophenyl)‐1,3‐dihydroisobenzofuran‐1‐yl]‐propyl}‐dimethylamine ([¹²⁵I]‐(S)‐2) were synthesized in a Br/¹²⁵I exchange reaction. Binding experiments in rats yielded K_d values of 0.7 ± 0.06 and 0.52 ± 0.02 nM for [¹²⁵I]‐2 and [¹²⁵I]‐(S)‐2, respectively. One hour after intravenous injection of [¹²⁵I]‐2, 0.34% of the injected dose had accumulated in the brain. The highest hypothalamus‐to‐cerebellum ratio was reached 2 h after injection of [¹²⁵I]‐(S)‐2 and amounted to 2.4. Pre‐treatment experiments with paroxetine resulted in effective reduction of the target‐to‐cerebellum ratios. The corresponding iodine‐123 labelled compound S‐[¹²³I]{3‐[5‐Iodo‐1‐(4‐fluorophenyl)‐1,3‐dihydroisobenzofuran‐1‐yl]‐propyl}‐dimethylamine [¹²³I]‐S‐ 2 was investigated in a pig single photon emission computed tomography (SPECT) study. Between 60 and 110 min after IV injection, the midbrain‐to‐cerebellum ratio was 1.2. However, the uptake did not differ between high‐density and medium‐density regions questioning the feasibility of the radioligand in imaging cortical SERT distribution in vivo. These data suggest that the iodine‐labelled derivatives of citalopram and escitalopram are not superior to another SPECT tracer for the SERT, namely [¹²³I]ADAM. Copyright © 2010 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.     

Synthesis and biological evaluation of a radioiodinated spiropiperidine ligand as a potential σ1 receptor imaging agent

We report the synthesis and evaluation of 1′‐(4‐[¹²⁵I]iodobenzyl)‐3H‐spiro[isobenzofuran‐1,4′‐piperidine] ([¹²⁵I]Spiro‐I) as a potential SPECT tracer for imaging of σ₁ receptors. [¹²⁵I]Spiro‐I was prepared in 55–65% isolated radiochemical yield, with radiochemical purity of >99%, via iododestannylation of the corresponding tributyltin precursor. In receptor binding studies, Spiro‐I displayed low nanomolar affinity for σ₁ receptors (σ₁: K_i=2.75±0.12 nM; σ₂: K_i=340 nM) and high subtype selectivity (σ₂/σ₁=124). Biodistribution in mice demonstrated relatively high concentration of radioactivity in organs known to contain σ₁ receptors, including the lung, kidney, heart, spleen, and brain. Administration of haloperidol 5 min prior to injection of [¹²⁵I]Spiro‐I significantly reduced the concentration of radioactivity in the above‐mentioned organs. These findings suggest that the binding of [¹²⁵I]Spiro‐I to σ₁ receptors in vivo is specific. Copyright © 2010 John Wiley & Sons, Ltd.     

Preclinical evaluation of new GnRH‐I receptor radionuclide therapy with 177Lu‐peptide tracer

The purpose of this study was to develop preclinical evaluation of a novel radiolabeled gonadotropin‐releasing hormone (GnRH) receptor targeting peptide for prostate cancer therapy. The new antiproliferative agent of GnRH‐I analogue was developed on the basis of the D‐Trp⁶‐GnRH‐I scaffold, and in vivo pharmacokinetics and receptor binding affinity were enhanced by the substitution of Gly‐NHNH₂ for Gly‐NH₂ at position 10 in D‐Trp⁶‐GnRH‐I. To evaluate ¹⁷⁷Lu‐DOTA‐triptorelin‐hydrazide as radionuclide therapy of tumor, the quality control tests and preclinical stage assessment were carried out. Solid‐phase method was used to synthesize new peptide. Characterization and purity of peptide were done by mass spectroscopy and high‐performance liquid chromatography (HPLC). In order to be utilized in targeted therapy, the new GnRH‐I agonist was coupled with pSCN‐Bn‐DOTA. The precipitate crude of DOTA‐triptorelin‐hydrazide was then purified via preparative HPLC. At optimal conditions of time, temperature, ligand amount, and lutetium content, DOTA‐triptorelin‐hydrazide was labeled with ¹⁷⁷Lu (specific activity not less than 925 GBq/mg). Investigation of the in vivo biodistribution and in vitro studies for ¹⁷⁷Lu‐DOTA‐TRPHYD was performed in three different ways, and the binding of radiopeptide to GnRH receptors was expressed on the human cell lines using ¹²⁵I‐labeled D‐TRP⁶GnRH‐I as a tracer, respectively. Synthesized novel GnRH‐I was obtained with purity greater than 98%. Paper chromatography was found to be the most suitable with R_f of the complex and observed radiochemical purity of RTLC and HPLC greater than 97%. For in vivo studies, ¹⁷⁷Lu‐DOTA‐triptorelin‐hydrazide showed promising results with fast clearance from the blood and resulted in good T/NT ratios at 1, 4, and 24 hours postinjection and satisfactory biodistribution with no significant activity seen in normal tissue. The values of internalization efficiency and receptor affinity of new radiopeptide binding were IC₅₀ = 0.47 ± 0.06 vs 0.13 ± 0.01 nM for triptorelin and cellular uptake: 3.4 ± 0.7% at 1 hour and 6.8 ± 1.17% at 4 hours of the internal reference. The results showed a good stability and radiochemical purity of the obtained radioconjugate. For in vivo and in vitro studies, new radiopeptide showed a high uptake of ¹⁷⁷Lu conjugate in tumor and rapid clearance from the blood stream almost entirely via the renal/urinary pathway and binding to the GnRH receptors with high specificity and affinity, respectively.     

Radioiodination and bioevaluation of rolipram as a tracer for brain imaging: In silico study,molecular modeling and gamma scintigraphy

Brain imaging is considered one of the most fruitful applications of radioisotope scanning. Rolipram, a selective phospodiesterase‐4 inhibitor, has been labeled using [¹²⁵I] with chloramine‐T (Ch‐T) as an oxidizing agent. Factors, such as the amount of substrate, pH, the amount of oxidizing agent, temperature, and the reaction time, have been systematically studied to optimize the iodination process. In addition, bio‐distribution studies have indicated that the brain uptake of [¹²⁵I]iodorolipram is 7.6 ± 0.33 injected dose/g organ at 10 minutes post‐injection, which cleared from the brain with time until it reaches 1.30 ± 0.17% at 1 hour post‐injection. Therefore, iodorolipram could be considered as a potential, new selective radiotracer for brain imaging.     

Radioiodination and biological evaluation of candesartan as a tracer for cardiovascular disorder detection

The goal of the study aims to evaluate newly radioiodinated candesartan (CAN) as a potential cardiovascular tracer. CAN was labeled using ¹²⁵I with chloramine‐T (Ch‐T) and N‐bromosuccinimide (NBS) with full characterization of cold Iodo‐candesartan. Factors such as pH, reaction temperature, reaction time, substrate, and oxidizing agent amounts were studied to optimize the radioiodination of CAN. The optimum radiochemical yield of ¹²⁵I‐CAN was 98%. The labeled compound was separated and purified using high‐pressure liquid chromatography. The biological distribution indicates the suitability of ¹²⁵I‐CAN as a novel tracer to detect cardiovascular disorders.     

Preparation of the iodine‐124 derivative of the Bolton–Hunter reagent ([124I]I‐SHPP) and its use for labelling a VEGF antibody as a PET tracer

This study describes the radioiodination of an antibody specific to the vascular endothelial growth factor (VEGF), VG76e, with [¹²⁴I]iodine to obtain a novel PET tracer for measurement of angiogenesis. In vitro binding assays showed a significantly higher immunoreactive fraction with the protein labelling reagent N‐succinimidyl 3‐(4‐hydroxy‐5‐[¹²⁵I]iodophenyl) propionate ([¹²⁵I]Bolton–Hunter reagent, [¹²⁵I]I‐SHPP) (34.0±4.0%) as compared with N‐succinimidyl 3‐[¹²⁵I]iodobenzoate (10.9±6.4%) or direct radioiodination using [¹²⁵I]iodide and IodoGen (3.1±3.0%). Consequently, the cyclotron–produced positron–emitting [¹²⁴I]iodine (T_1/2=4.2 days) was employed to prepare [¹²⁴I]I‐SHPP. Using an improved radioiodination methodology, [¹²⁴I]I‐SHPP was prepared from sodium [¹²⁴I]iodide with IodoGen at pH 6.5. The [¹²⁴I]Bolton–Hunter reagent was isolated with 25–58% (n=3) radiochemical yield and 88–95% (n=3) radiochemical purity by the conventional extraction procedure. The conjugate of VG76e with [¹²⁴I]I‐SHPP was prepared with 17–18% (n=3) labelling efficiency and 98% radiochemical purity. The immunoreactive fraction was determined to be 33.5% (n=2). Copyright © 2002 John Wiley & Sons, Ltd.     

A tin precursor for the synthesis of no‐carrier‐added [*I]MIBG and [211At]MABG

Radioiodinated MIBG has shown considerable promise as an imaging agent for cardiac and oncologic applications, and also as a targeted radiotherapeutic for treating patients with neuroendocrine tumors. This radiolabeled agent, synthesized at a no‐carrier‐added level, has demonstrated advantages over the carrier‐added preparation in preliminary clinical studies. Earlier we developed a silicon precursor from which both radioiodinated MIBG and the α‐particle‐emitting ²¹¹At analog [²¹¹At]MABG could be synthesized at a no‐carrier‐added level. In order to increase the practicality of this approach, we have developed a synthesis of a tin precursor in two steps from a readily available starting material. This tin precursor, N, N′‐bis(tert‐butyloxycarbonyl)‐3‐(trimethylstannyl)benzylguanidine (Bis‐Boc MTMSBG) was evaluated for the synthesis of n.c.a. [*I]MIBG and [²¹¹At]MABG via halodestannylation. The radiochemical yields were 83 ± 9% (n=7), 30 ± 21% (n=2), 77 ± 2% (n=2), and 66 ± 7% (n=4) for labeling with ¹³¹I, ¹²⁴I, ¹²⁵I, and ²¹¹At, respectively. Copyright © 2007 John Wiley & Sons, Ltd.     

Synthesis,quality control and in vivo evaluation of [123I] rhTIMP‐2, a potential tumour‐imaging agent

Matrix metalloproteinases (MMPs) are enzymes involved in the turnover of the extracellular matrix. Their overexpression in tumours may provide a target for diagnostic imaging by using labelled MMP inhibitors. MMPs are inhibited by endogenous tissue inhibitors of metalloproteinases (TIMPs). The enhanced production of MT1‐MMP, located on the surface of cells within or in the direct vicinity of the tumour, and the high affinity interaction between TIMP‐2 and MT1‐MMP suggested that TIMP‐2 could be a potential agent for non‐invasive monitoring of cancer MMP levels, diagnosis of primary and secondary tumours and tumour response to MMP inhibitor therapy. There is also evidence that ¹²⁵I‐rhTIMP‐2 internalizes, which is an important feature for its possible use as a radiotherapeuticum if labelled with ¹³¹I. Labelling of rhTIMP‐2 was performed using the iodogen method resulting in a radiochemical yield of 51.1±11.8% (n=5) and a radiochemical purity of >98%. The trichloroacetic acid (TCA) precipitability of ¹²³I rhTIMP‐2 was 95.2%. SDS‐PAGE confirmed the correct size (21 kDa) of the purified ¹²³I rhTIMP‐2 without degradation. HPLC showed one radioactive peak with a retention time corresponding to the non‐labelled rhTIMP‐2. In vivo biodistribution showed no long‐term accumulation in organs and the possibility to accumulate in the tumour. These results show the potential of ¹²³I rhTIMP‐2 as tumour‐imaging agent. Copyright © 2005 John Wiley & Sons, Ltd.     

Radiosynthesis and in vitro evaluation of 1‐(tetrahydro‐5‐hydroxy‐6‐(hydroxymethyl)‐2H‐pyran‐3‐yl)‐5‐[125I]iodouracil: A new potential agent for HSV1‐tk reporter gene monitoring

Synthesis, radiolabelling, and in vitro evaluation of a new ¹²⁵I‐labelled iodouracil hexitol nucleoside analogue are reported. The target compound was successfully synthesized by an iodination–destannylation method and then purified by reverse phase HPLC. The radiochemical purity of the product was >99% with decay‐corrected yields of 48±3%. In vitro cellular uptake testing was carried out using MCA and MCA‐tk cell lines for comparison of compound 1 with [¹⁸F]FHBG. The newly synthesized compound 1 showed higher accumulation in herpex simplex virus type 1 thymidine kinase (HSV1‐tk) gene expression cell line (MCA‐tk cell line) than in the wild type MCA cell line compared with [¹⁸F]FHBG. The MCA‐tk to MCA cellular uptake ratio for compound 1 was higher than that of [¹⁸F]FHBG from 2 h after incubation. The radioiodine‐labelled compound 1 (I‐125, t_1/2=59.37 days) has a longer physical half‐life than F‐18‐(t_1/2=110 min) labelled FHBG. Radioiodine‐labelled compound 1 could be used for monitoring gene expression for a long time. The selectivity for MCA‐tk cell line makes compound 1 a promising imaging agent for HSV1‐tk expression. Copyright © 2010 John Wiley & Sons, Ltd.     

Radioiodination and biological evaluation of nizatidine as a new highly selective radiotracer for peptic ulcer disorder detection

Nizatidine has been labeled using [¹²⁵I] with chloramine‐T as oxidizing agent. Factors such as the amount of oxidizing agent, amount of substrate, pH, reaction temperature, and reaction time have been systematically studied to optimize the iodination. Biodistribution studies indicate the suitability of radioiodinated nizatidine as a novel tracer to image stomach ulcer. Radioiodinated nizatidine may be considered a highly selective radiotracer for peptic ulcer imaging.     

6‐[(2‐Iminopyrrolidinyl)methyl]‐5‐[125I]iodouracil as a potential thymidine phosphorylase‐targeted radiopharmaceutical: synthesis and preliminary biological evaluation

Thymidine phosphorylase (TP) is expressed at higher levels in many types of malignant tumors than in adjacent nonneoplastic tissues. The aim of this study was to develop a radiolabeled TP inhibitor, 6‐[(2‐iminopyrrolidinyl)methyl]‐5‐[¹²⁵I]iodouracil ([¹²⁵I]1) as a TP‐targeted radiopharmaceutical. No‐carrier‐added [¹²⁵I]1 was synthesized by halogen exchange of the corresponding bromide (2). After purification by reverse‐phase HPLC, [¹²⁵I]1 showed a radiochemical purity of over 97%. When administered to normal mice, [¹²⁵I]1 showed a rapid clearance from the blood and a low accumulation in the thyroid and stomach, indicating good in vivo stability against deiodination. By coinjection of unlabeled 1, the uptakes in the TP‐expressing normal tissues, small intestine and liver were significantly reduced, suggesting TP‐specific modes of accumulation of [¹²⁵I]1. These findings suggest that [¹²⁵I]1 possesses the required properties for in vivo imaging of TP activity. Copyright © 2009 John Wiley & Sons, Ltd.     

An investigation of the 125I‐radioiodination of colchicine for medical purposes

A procedure for radioiodination of colchicine with iodine‐125 is carried out via an electrophilic substitution reaction. The reaction parameters studied were colchicine concentration, pH of the reaction mixture, reaction time, temperature, different oxidizing agents and different organic media to optimize the conditions for the labeling of colchicine and to obtain a high radiochemical yield of the ¹²⁵I‐colchicine (¹²⁵I‐Col). Using 3.7 MBq of Na¹²⁵I, 1.25 mM of colchicine as substrate, 1.1 mM of chloramine‐T (CAT) as oxidizing agent in ethanol at 60°C for 5 min, a maximum radiochemical yield of ¹²⁵I‐Col (60%) was obtained. The specific activity of ¹²⁵I‐Col obtained was 44.4 MBq/0.5 mmol, and the labeled compound was not completely separated and purified from Col by means of high‐pressure liquid chromatography (HPLC), so the uncertainty in the purity may affect the distribution and clearance routes due to the expected competition between ¹²⁵I‐Col and Col. The biological distribution in normal mice indicates the suitability of radioiodinated colchicine for imaging of muscles. Copyright © 2008 John Wiley & Sons, Ltd.     

A Putative Single-Photon Emission CT Imaging Tracer for Erythropoietin-Producing Hepatocellular A2 Receptor

Erythropoietin-producing hepatocellular (Eph) receptors are receptor tyrosine kinases involved in cell–cell contact. The EphA2 receptor is associated with cancer proliferation and migration. Therefore, EphA2 receptor imaging has the potential for cancer diagnosis. Here, we synthesized N-(5-((4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)carbamoyl)-2-methylphenyl)-5-[¹²³I]iodonicotinamide ([¹²³I]ETB) and evaluated it as an imaging tracer for single-photon emission computed tomography (SPECT) imaging of the EphA2 receptor. [¹²³I]ETB was designed on the basis of ALW-II-41-27, an inhibitor of EphA2 receptor kinase. Nonradioactive ETB was also synthesized and has been shown to efficiently inhibit EphA2 receptor kinase activity in vitro (IC₅₀: ETB, 90.2 ± 18.9 nM). A cell-binding assay demonstrated that [¹²⁵I]ETB binds specifically to the EphA2 receptor. The ex vivo biodistribution study of [¹²⁵I]ETB in U87MG tumor-bearing mice also revealed tumor uptake (2.2% ID/g at 240 min). In addition, [¹²³I]ETB uptake in tumors was visualized via SPECT/CT imaging. On the basis of the above, [¹²³I]ETB can be considered a potential SPECT imaging tracer for the EphA2 receptor.     

Synthesis of a radioiodinated thymidine phosphorylase inhibitor and its preliminary evaluation as a potential SPECT tracer for angiogenic enzyme expression

The expression of thymidine phosphorylase (TP) is strongly associated with angiogenesis in tumors and activation of antitumor agents. We designed a novel 5‐¹²⁵I‐labeled 6‐(2‐iminoimidazolidinyl)methyluracil hydrochloride ([¹²⁵I]5I6IMU‐HCl) to develop an effective radiotracer for in vivo assessment of TP expression in tumors and prognosis of cancer chemotherapy. Radiotracer synthesis was achieved by radioiodination of the precursor, 6‐(2‐iminoimidazolidinyl)methyluracil at the C‐5 position with NCS/radioiodide. After purification by HPLC, [¹²⁵I]5I6IMU‐HCl was obtained in high radiochemical yield with satisfactory specific activity. The radiotracer showed high inhibitory potency for the target enzyme and good stability in vivo. Copyright © 2008 John Wiley & Sons, Ltd.     

Synthesis of a new fluorine‐18 glycosylated ‘click’ cyanoquinoline for the imaging of epidermal growth factor receptor

This study reports the radiosynthesis of a new fluorine‐18 glycosylated ‘click’ cyanoquinoline [¹⁸F]5 for positron emission tomography imaging of epidermal growth factor receptor (EGFR). The tracer was obtained in 47.7 ± 7.5% (n = 3) decay‐corrected radiochemical yield from 2‐[¹⁸F]fluoro‐2‐deoxy‐β‐d ‐glucopyranosyl azide, and the overall nondecay‐corrected radiochemical yield from aqueous fluoride was 8.6 ± 2.3% (n = 3). An in vitro preliminary cellular uptake study showed selectivity of the tracer for EGFR‐positive A431 cell lines versus EGFR‐negative MCF‐7 cell lines. [¹⁸F]5 tracer uptake in A431 cells was significantly reduced by addition of the cold isotope analogue compound 5.