Quantitative Molecular Imaging Research Articles

Quantitative molecular imaging of atherosclerotic endothelial dysfunction with perfluorocarbon (19F) nanoparticle magnetic resonance imaging and spectroscopy

Methods Five NZW rabbits were fed a high fat diet for 9-12 months (cholesterol: 1200-1700 mg/dL). Fluorescently-labeled, nontargeted NP were injected (2 ml/kg) intravenously into rabbit ear vein. After circulation in vivo for 1, 6 or 24 hours, aortas were excised for 19F MRI and spectroscopy (Varian 11.7 T scanner); and whole mount fluorescence imaging (Xenogen IVIS system). Two human carotid endarterectomy tissues were collected from operation room. After pretreatment with plasmin to digest fibrin on the endothelial surface and incubation with nontargeted NP for 6 hours, tissues were rinsed and formalin fixed for 19F MRI and spectroscopy. A perfluorooctyl bromide standard enabled MRS-based quantification of NP concentration in each imaged voxel. Results In rabbit aortas, MRI (19F/1H overlay) revealed abundant 19F signal from intact NP that were localized heterogeneously in the plaque interstitium (Fig. 1A) but not in unaffected areas. The average tissue concentration of NP calculated from MR spectroscopy (Fig. 1B) was 2.36 ± 0.42 × 109 /g aorta. The accumulation of NP is distinct from macrophage uptake, as demonstrated by high resolution fluorescence microscopy (Fig. 1C). Fluorescence imaging (Fig. 1D) also confirmed the presence of NP. In human carotid arterectomy tissues, the detected 19F signals were primary located on the endothelial/luminal side (Fig. 2). Quantitative analysis showed that average NP concentration in carotid arterectomy tissue was 47.1 ± 18.3 × 109 /g tissue.

Metabolic toxicity of the heart: Insights from molecular imaging

There is convincing evidence that alterations in myocardial substrate use play an important role in the normal and diseased heart. In this review, insights gained by using quantitative molecular imaging by positron emission tomography and magnetic resonance spectroscopy in the study of human myocardial metabolism will be discussed, and attention will be paid to the effects of nutrition, gender, aging, obesity, diabetes, cardiac hypertrophy, ischemia, and heart failure. The heart is an omnivore organ, relying on metabolic flexibility, which is compromised by the occurrence of defects in coronary flow reserve, insulin-mediated glucose disposal, and metabolic-mechanical coupling. Obesity, diabetes, and ischemic cardiomyopathy appear as states of high uptake and oxidation of fatty acids, that compromise the ability to utilize glucose under stimulated conditions, and lead to misuse of energy and oxygen, disturbing mechanical efficiency. Idiopathic heart failure is a complex disease frequently coexisting with diabetes, insulin resistance and hypertension, in which the end stage of metabolic toxicity manifests as severe mitochondrial disturbance, inability to utilize fatty acids, and ATP depletion. The current literature provides evidence that the primary events in the metabolic cascade outlined may originate in extra-cardiac organs, since fatty acid, glucose levels, and insulin action are mostly controlled by adipose tissue, skeletal muscle and liver, and that a broader vision of organ cross-talk may further our understanding of the primary and the adaptive events involved in metabolic heart toxicity.

Probing dynamic fluorescence properties of single and clustered quantum dots toward quantitative biomedical imaging of cells

We present results on the dynamic fluorescence properties of bioconjugated nanocrystals or quantum dots (QDs) in different chemical and physical environments. A variety of QD samples was prepared and compared: isolated individual QDs, QD aggregates, and QDs conjugated to other nanoscale materials, such as single-wall carbon nanotubes (SWCNTs) and human erythrocyte plasma membrane proteins. We discuss plausible scenarios to explain the results obtained for the fluorescence characteristics of QDs in these samples, especially for the excitation time-dependent fluorescence emission from clustered QDs. We also qualitatively demonstrate enhanced fluorescence emission signals from clustered QDs and deduce that the band 3 membrane proteins in erythrocytes are clustered. This approach is promising for the development of QD-based quantitative molecular imaging techniques for biomedical studies involving biomolecule clustering.

Efficient microwave-assisted direct radiosynthesis of [ 18F]PR04.MZ and [ 18F]LBT999: Selective dopamine transporter ligands for quantitative molecular imaging by means of PET

PR04.MZ 8-(4-fluoro-but-2-ynyl)-3- p-tolyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid methyl ester ( 1) and LBT999 8-(( E)-4-fluoro-but-2-enyl)-3b- p-tolyl-8-aza-bicyclo[3.2.1]octane-2β-carboxylic acid methyl ester ( 2) are selective dopamine reuptake inhibitors, derived from cocaine. Compounds 1 and 2 were labelled with fluorine-18 at their terminally fluorinated N-substituents employing microwave enhanced direct nucleophilic fluorination. K[ 18F]F − Kryptofix ®222 cryptate, tetrabutyl ammonium [ 18F]fluoride and caesium [ 18F]fluoride were compared as fluoride sources under conventional and microwave enhanced conditions. Fluorination yields were remarkably increased under microwave irradiation for all three fluoride salts. Radiochemically pure (>98%) [ 18F]PR04.MZ (0.95–1.09 GBq, 42–135 GBq/μmol) was obtained within 34–40 min starting from 3.0 GBq [ 18F]fluoride ion in 32–36% non-decay-corrected overall yield using K[ 18F]F −Kryptofix ®222 cryptate in MeCN.

Quantitative Endovascular Fluorescence-based Molecular Imaging through Blood of Arterial Wall Inflammation

To evaluate an author-developed normalization algorithm for quantitative imaging of optical molecular probes through blood and to assess, in the rat aorta after focal aortic injury, the feasibility of measuring protease activity by using this method. This study was performed according to a protocol approved by the institutional animal care committee. A Monte Carlo simulation was used to determine the pair of near-infrared (NIR) dyes that was best suited for the normalization algorithm. The authors tested the correction method in vitro and in vivo by injecting free dye mixtures intramurally in the aortas of four rats. The potential clinical utility was then evaluated by applying the method to the endovascular measurement of protease activity in a rat model of focal aortic injury. When the Monte Carlo simulation was used in the normalization algorithm, it was predicted that the intensities of signals from two NIR dyes would vary +/-3% across 1 mm of blood compared with the intensity of the raw fluorochrome signal, which would vary +/-60%. This result was validated in vitro. Endovascular imaging of free dye collections revealed that clinically relevant, uncontrollable differences in the amount of blood intervening between the imaging catheter and the dye collection precipitated dramatic variations in raw NIR fluorescence. However, use of the correction method resolved these variations such that the measured signal intensity correlated well with the different dye concentrations in the different animals. Moreover, endovascular imaging of the focal aortic injury model enabled successful measurement of enzyme activity in the walls of the rat aortas. The authors implemented a correction method for quantitative real-time endovascular imaging of fluorescence that enables one to resolve the attenuating effects of blood on NIR signal.

Perfluorocarbon Nanoemulsions for Quantitative Molecular Imaging and Targeted Therapeutics

A broad array of nanomaterials is available for use as contrast agents for molecular imaging and drug delivery. Due to the lack of endogenous background signal in vivo and the high NMR sensitivity of the (19)F atom, liquid perfluorocarbon nanoemulsions make ideal agents for cellular and magnetic resonance molecular imaging. The perfluorocarbon core material is surrounded by a lipid monolayer which can be functionalized with a variety of agents including targeting ligands, imaging agents and drugs either individually or in combination. Multiple copies of targeting ligands (approximately 20-40 monoclonal antibodies or 200-400 small molecule ligands) serve to enhance avidity through multivalent interactions while the composition of the particle's perfluorocarbon core results in high local concentrations of (19)F. Additionally, lipophilic drugs contained within molecularly targeted nanoemulsions can result in contact facilitated drug delivery to target cells. Ultimately, the dual use of perfluorocarbon nanoparticles for both site targeted drug delivery and molecular imaging may provide both imaging of disease states as well as conclusive evidence that drug delivery is localized to the area of interest. This review will focus on liquid perfluorocarbon nanoparticles as (19)F molecular imaging agents and for targeted drug delivery in cancer and cardiovascular disease.

Molecular imaging of α7 nicotinic acetylcholine receptors: design and evaluation of the potent radioligand [18F]NS10743

The outstanding diversity of cellular properties mediated by neuronal and nonneuronal alpha7 nicotinic acetylcholine receptors (alpha7 nAChR) points to the diagnostic potential of quantitative nuclear molecular imaging of alpha7 nAChR in neurology and oncology. It was our goal to radiolabel the alpha7 nAChR agonist 4-[5-(4-fluoro-phenyl)-[1,3,4]oxadiazol-2-yl]-1,4-diaza-bicyclo[3.2.2]nonane (NS10743) and to assess the selectivity of [(18)F]NS10743 binding site occupancy in animal experiments. [(18)F]NS10743 was synthesized by nucleophilic substitution of the nitro precursor. In vitro receptor affinity and selectivity were assessed by radioligand competition and autoradiography. The radiotracer properties were evaluated in female CD-1 mice by brain autoradiography and organ distribution. Target specificity was validated after treatment with SSR180711 (10 mg/kg, intraperitoneal), and metabolic stability was investigated using radio-HPLC. The specific activity of [(18)F]NS10743 exceeded 150 GBq/micromol at a radiochemical purity >99%. In vitro, NS10743 and [(18)F]NS10743 showed high affinity and specificity towards alpha7 nAChR. The brain permeation of [(18)F]NS10743 was fast and sufficient with values of 4.83 and 1.60% injected dose per gram and brain to plasma ratios of 3.83 and 2.05 at 5 and 60 min after radiotracer administration. Brain autoradiography and organ distribution showed target-specific accumulation of [(18)F]NS10743 in brain substructures and various alpha7 nAChR-expressing organs. The radiotracer showed a high metabolic stability in vivo with a single polar radiometabolite, which did not cross the blood-brain barrier. The good in vitro and in vivo features of [(18)F]NS10743 make this radioligand a promising candidate for quantitative in vivo imaging of alpha7 nAChR expression and encourage further investigations.

Quantitative Molecular Imaging of Viral Therapy for Pancreatic Cancer Using an Engineered Measles Virus Expressing the Sodium-Iodide Symporter Reporter Gene

Our objectives were to, first, determine the oncolytic potential of an engineered measles virus expressing the sodium-iodide symporter gene (MV-NIS) for intratumoral (i.t.) therapy of pancreatic cancer and, second, evaluate NIS as a reporter gene for in vivo monitoring and quantitation of MV-NIS delivery, viral spread, and gene expression in this tumor model. Cultured human pancreatic cancer cells were infected with MV-NIS. Light microscopy, cell viability, and iodide uptake assays were used to confirm viral infection and NIS gene expression and function in vitro. Human pancreatic tumor xenografts were established in mice and infected via i.t. MV-NIS injections. NIS-mediated i.t. iodide uptake was quantitated by (123)I micro-SPECT/CT. i.t. MV-NIS infection was confirmed by immunohistochemistry of excised pancreatic xenografts. The oncolytic efficacy of MV-NIS was determined by measurement of tumor growth and mouse survival. Infection of human pancreatic cancer cell lines with MV-NIS in vitro resulted in syncytia formation, marked iodide uptake, and ultimately cell death. Tumor xenografts infected with MV-NIS concentrated radioiodine, allowing serial quantitative imaging with (123)I micro-SPECT/CT. i.t. MV-NIS therapy of human pancreatic cancer xenografts resulted in a significant reduction in tumor volume and increased survival time of the treated mice compared with the control mice. MV-NIS efficiently infects human pancreatic tumor cells and results in sufficient radioiodine uptake to enable noninvasive serial imaging and quantitation of the intensity, distribution, and time course of NIS gene expression. MV-NIS also shows oncolytic activity in human pancreatic cancer xenografts: Tumor growth is reduced and survival is increased in mice treated with the virus.

Abstract 2238: New Pharmacokinetic Models for Quantitative Molecular Imaging of Plaque Angiogenesis with Intergrin-targeted Nanoparticles

Cardiovascular molecular imaging with targeted nanoparticles has emerged as a promising method for early detection of atherosclerosis and vulnerable plaque. However, traditional pharmacokinetic models for diffusible drugs are inadequate to describe the efficacy of nanoparticle carriers of diagnostic and therapeutic cargos. To quantify blood and MRI tissue signals from gadolinium-loaded nanoparticles (Gd-NP) targeted to avb3 integrins expressed on angiogenic capillaries in the aortas of cholesterol-fed rabbit, a novel 4 compartment open PK model was developed that utilized a unique simultaneous fitting scheme. In 10 rabbits fed 0.25% cholesterol for 3 months, the concentration of nanoparticles was measured serially from blood samples after injection of 1 ml/kg of targeted or nontargeted Gd-NP. The MRI proton signatures emanating from nanoparticles bound to the expanded vasa vasorum of the descending thoracic aorta was computed for all aortic cross sections in 1.5T T1w fa-suppressed spin-echo images. Based on the PK analysis, the concentration of targeted nanoparticles in the aortic wall is double that of non-targeted nanoparticles. Notably, this signal enhancement is achieved with 20x less gadolinium (4.6x10 −3 mmol Gd/kg BW) as compared with the dose of conventional gadolinium agents (0.1 mmol/kg). Further, the PK analysis shows that the targeted nanoparticles are more than three times more effective at reaching the aortic wall. These results should facilitate development and use of nanotechnologies intended for early detection of atherosclerosis and provide enhanced understanding of the kinetics and mechanisms of active targeting of plaque angiogenesis.

Imaging of EGFR and EGFR tyrosine kinase overexpression in tumors by nuclear medicine modalities.

Protein tyrosine kinases (PTKs) play a pivotal role in signal transduction pathways and in the development and maintenance of various cancers. They are involved in multiple processes such as transcription, cell cycle progression, proliferation, angiogenesis and inhibition of apoptosis. Among the PTKs, the EGFR is one of the most widely studied and has emerged as a promising key target for the treatment of cancer. Indeed, several drugs directed at this receptor are FDA-approved and many others are at various stages of development. However, thus far, the therapeutic outcome of EGFR-targeted therapy is suboptimal and needs to be refined. Quantitative PET molecular imaging coupled with selective labelled biomarkers may facilitate in vivo EGFR-targeted drug efficacy by noninvasively assessing the expression of EGFR in tumor, guiding dose and regime by measuring target drug binding and receptor occupancy as well as potentially detecting the existence of a primary or secondary mutation leading to either drug interaction or failure of EGFR recognition by the drug. This review describes the attempts to develop labelled EGFR molecular imaging agents that are based either on low molecular weight tyrosine kinase inhibitors or monoclonal antibodies directed to the extracellular binding domain of the receptor to be used in nuclear medicine modalities.

Multimodality Molecular Imaging of Tumor Angiogenesis

Molecular imaging is a key component of 21st-century cancer management. The vascular endothelial growth factor (VEGF)/VEGF receptor signaling pathway and integrin alpha v beta 3, a cell adhesion molecule, play pivotal roles in regulating tumor angiogenesis, the growth of new blood vessels. This review summarizes the current status of tumor angiogenesis imaging with SPECT, PET, molecular MRI, targeted ultrasound, and optical techniques. For integrin alpha v beta 3 imaging, only nanoparticle-based probes, which truly target the tumor vasculature rather than tumor cells because of poor extravasation, are discussed. Once improvements in the in vivo stability, tumor-targeting efficacy, and pharmacokinetics of tumor angiogenesis imaging probes are made, translation to clinical applications will be critical for the maximum benefit of these novel agents. The future of tumor angiogenesis imaging lies in multimodality and nanoparticle-based approaches, imaging of protein-protein interactions, and quantitative molecular imaging. Combinations of multiple modalities can yield complementary information and offer synergistic advantages over any modality alone. Nanoparticles, possessing multifunctionality and enormous flexibility, can allow for the integration of therapeutic components, targeting ligands, and multimodality imaging labels into one entity, termed "nanomedicine," for which the ideal target is tumor neovasculature. Quantitative imaging of tumor angiogenesis and protein-protein interactions that modulate angiogenesis will lead to more robust and effective monitoring of personalized molecular cancer therapy. Multidisciplinary approaches and cooperative efforts from many individuals, institutions, industries, and organizations are needed to quickly translate multimodality tumor angiogenesis imaging into multiple facets of cancer management. Not limited to cancer, these novel agents can also have broad applications for many other angiogenesis-related diseases.

β2-Adrenergic Receptor Signaling and Desensitization Elucidated by Quantitative Modeling of Real Time cAMP Dynamics

G protein-coupled receptor signaling is dynamically regulated by multiple feedback mechanisms, which rapidly attenuate signals elicited by ligand stimulation, causing desensitization. The individual contributions of these mechanisms, however, are poorly understood. Here, we use an improved fluorescent biosensor for cAMP to measure second messenger dynamics stimulated by endogenous beta(2)-adrenergic receptor (beta(2)AR) in living cells. beta(2)AR stimulation with isoproterenol results in a transient pulse of cAMP, reaching a maximal concentration of approximately 10 microm and persisting for less than 5 min. We investigated the contributions of cAMP-dependent kinase, G protein-coupled receptor kinases, and beta-arrestin to the regulation of beta(2)AR signal kinetics by using small molecule inhibitors, small interfering RNAs, and mouse embryonic fibroblasts. We found that the cAMP response is restricted in duration by two distinct mechanisms in HEK-293 cells: G protein-coupled receptor kinase (GRK6)-mediated receptor phosphorylation leading to beta-arrestin mediated receptor inactivation and cAMP-dependent kinase-mediated induction of cAMP metabolism by phosphodiesterases. A mathematical model of beta(2)AR signal kinetics, fit to these data, revealed that direct receptor inactivation by cAMP-dependent kinase is insignificant but that GRK6/beta-arrestin-mediated inactivation is rapid and profound, occurring with a half-time of 70 s. This quantitative system analysis represents an important advance toward quantifying mechanisms contributing to the physiological regulation of receptor signaling.

Sleep deprivation predisposes liver to oxidative stress and phospholipid damage: a quantitative molecular imaging study

Sleep disorders are associated with an increased rate of various metabolic disturbances, which may be related to oxidative stress and consequent lipid peroxidation. Since hepatic phosphatidylcholine plays an important role in metabolic regulation, the aim of the present study was to determine phosphatidylcholine expression in the liver following total sleep deprivation. To determine the effects of total sleep deprivation, we used adult rats implanted for polygraphic recording. Phosphatidylcholine expression was examined molecularly by the use of time-of-flight secondary ion mass spectrometry, along with biochemical solid-phase extraction. The parameters of oxidative stress were investigated by evaluating the hepatic malondialdehyde levels as well as heat shock protein 25 immunoblotting and immunohistochemistry. In normal rats, the time-of-flight secondary ion mass spectrometry spectra revealed specific peaks (m/z 184 and 224) that could be identified as molecular ions for phosphatidylcholine. However, following total sleep deprivation, the signals for phosphatidylcholine were significantly reduced to nearly one-third of the normal values. The results of solid-phase extraction also revealed that the phosphatidylcholine concentration was noticeably decreased, from 15.7 micromol g-1 to 9.4 micromol g-1, after total sleep deprivation. By contrast, the biomarkers for oxidative stress were drastically up-regulated in the total sleep deprivation-treated rats as compared with the normal ones (4.03 vs. 1.58 nmol mg-1 for malondialdehyde levels, and 17.1 vs. 6.7 as well as 1.8 vs. 0.7 for heat shock protein 25 immunoblotting and immunoreactivity, respectively). Given that phosphatidylcholine is the most prominent component of all plasma lipoproteins, decreased expression of hepatic phosphatidylcholine following total sleep deprivation may be attributed to the enhanced oxidative stress and the subsequent lipid peroxidation, which would play an important role in the formation or progression of total sleep deprivation-induced metabolic diseases.

Smart optical probes for near-infrared fluorescence imaging of Alzheimer’s disease pathology

Near-infrared fluorescent probes for amyloid-beta (Abeta) are an exciting option for molecular imaging in Alzheimer's disease research and may translate to clinical diagnostics. However, Abeta-targeted optical probes often suffer from poor specificity and slow clearance from the brain. We are designing smart optical probes that emit characteristic fluorescence signal only when bound to Abeta. We synthesized a family of dyes and tested Abeta-binding sensitivity with fluorescence spectroscopy and tissue-staining. Select compounds exhibited Abeta-dependent changes in fluorescence quantum yield, lifetime, and emission spectra that may be imaged microscopically or in vivo using new lifetime and spectral fluorescence imaging techniques. Smart optical probes that turn on when bound to Abeta will improve amyloid detection and may enable quantitative molecular imaging in vivo.

Quantitative Real-time Catheter-based Fluorescence Molecular Imaging in Mice

To prospectively evaluate an optical imaging system designed to perform quantitative, intravital catheter-based imaging of fluorescent molecular probes. This study was performed according to a protocol approved by the institutional animal care committee. A fiberoptic catheter imaging system was developed to implement a normalization algorithm for real-time quantitative near-infrared (NIR) imaging. The system was validated with in vitro imaging of fluorochrome phantoms and in vivo fluorescence measurements obtained in tumors implanted in murine abdomens (n = 7) after administration of an enzyme-activatable NIR probe. Standard analysis of variance tests were used to determine significant dissimilarities in signal from distinct fluorochrome concentrations. The clinical utility of the system was further evaluated by imaging orthotopically implanted murine colonic adenocarcinomas (n = 4). Raw NIR fluorescence intensities, which were measured with a fiberoptic catheter placed above wells of varying NIR fluorochrome concentration, varied markedly (>100%) with catheter position, while the corrected NIR signal was confined to a range of values within 10% of their mean for each individual fluorochrome concentration and were significantly distinct (P < .001) between relevant concentration ranges. Similar results were observed for the in vivo measurements from the abdominally implanted tumors, with raw NIR signal varying 20% from the mean and corrected NIR signal varying only 1% from the mean. The colonic studies revealed that the correction method was robust enough for use during minimally invasive imaging procedures. The authors have developed and implemented a method for quantitative real-time catheter-based fluorescence imaging that resolves NIR signal dependence on changes in catheter position.

Is It Possible to Quantify Fluorescence during Optical Endoscopy?

Quantitative fluorescence molecular imaging can be performed by compensating for variations in the light intensity caused by a change in the position of the endoscope. By according for these differences, quantitation of fluorescence can be used to assess the biologic importance of a lesion that might not otherwise be detected with white light endoscopy. This area of inquiry represents an important new step toward the detection of disease in its earliest phases when it can be treated with minimally invasive surgery or ablation.

Autoradiography: high-resolution molecular imaging in pharmaceutical discovery and development

Autoradiography (ARG) is a powerful, high resolution, quantitative molecular imaging technique used to study the tissue distribution of radiolabeled xenobiotics in biologic models. ARG involves the close apposition of solid specimens containing a radiolabeled substance to a detector layer, such as photographic emulsions, film, phosphor imaging plates and direct nuclear imagers/counters. The two basic types include: macroautoradiography, which is imaging of organs, organ systems and/or whole-body sections (WBA) and microautoradiography (MARG), which provides the localization of radioactivity at the cellular level. ARG has supported drug discovery and development efforts for many years and has provided pivotal decision making information for pharmaceutical research. This paper presents a review of the techniques, study designs and present considerations for use of WBA and MARG to support today’s drug discovery and development efforts. In addition, this review comments on the integration of the ex vivo ARG and in vivo molecular imaging techniques to serve pharmaceutical discovery and development in the future.

Currents: In vivo volumetric optical microscopy for diagnostic imaging | A hybrid microfluidic system for screening and optimization | Quantitative molecular imaging in mouse organs | Subdiffraction imaging with PAINT | An ultrasensitive nanocatalyst disease proteins | Fast movements watched by 2D IR spectroscopy

Currents: In vivo volumetric optical microscopy for diagnostic imaging | A hybrid microfluidic system for screening and optimization | Quantitative molecular imaging in mouse organs | Subdiffraction imaging with PAINT | An ultrasensitive nanocatalyst disease proteins | Fast movements watched by 2D IR spectroscopy

Chiral dimethylamine flutamide derivatives—modeling, synthesis, androgen receptor affinities and carbon-11 labeling

Most prostate cancers are androgen dependent upon initial diagnosis. On the other hand, some very aggressive forms of prostate cancer were shown to have lost the expression of the androgen receptor (AR). Although the AR is routinely targeted in endocrine treatment, the clinical outcome remains suboptimal. Therefore, it is crucial to demonstrate the presence and activity of the AR in each case of prostate cancer, before and after treatment. While noninvasive positron emission tomography (PET) has the potential to determine AR expression of tumor cells in vivo, fully optimized PET imaging agents are not yet available. Based on molecular modeling, three novel derivatives of hydroxyflutamide (Compounds 1-3) were designed and synthesized. They contain an electron-rich group (dimethylamine) located on the methyl moiety, which may confer a better stability to the molecule in vivo. Compounds 1-3 have AR binding that is similar or higher than that of the currently used commercial drugs. An automated carbon-11 radiolabeling route was developed, and the compounds were successfully labeled with a 10-15% decay-corrected radiochemical yield, 99% radiochemical purity and a specific activity of 4Ci/mumol end of bombardment (n=15). These labeled biomarkers may facilitate the future quantitative molecular imaging of AR-positive prostate cancer using PET and may also allow for image-guided treatment of prostate cancer.

Clinical molecular imaging with positron emission tomography

Molecular imaging allows for the in vivo evaluation of targeted molecules and biological processes in man. Positron emission tomography (PET) is a highly sensitive and quantitative molecular imaging modality, whose utility in clinical and experimental medicine is increasing by the day. In this article, the principles of PET and its currently accepted applications in oncology, such as cancer staging, treatment response assessment and as a prognostic marker are reviewed. Further, the evolving role of PET in areas of oncology such as radiotherapy treatment planning, anti-cancer drug development and the evaluation of patho-physiological processes which drive a cell into neoplastic activity is discussed.