Specific Molecular Imaging Research Articles

Hypoxia-specific ultrasensitive detection of tumours and cancer cells in vivo

Highly sensitive and specific non-invasive molecular imaging methods are particularly desirable for the early detection of cancers. Here we report a near-infrared optical imaging probe highly specific to the hypoxic tumour microenvironment to detect tumour and cancer cells with the sensitivity to a few thousands cancer cells. This oxygen-sensitive, near-infrared emitting and water-soluble phosphorescent macromolecular probe can not only report the hypoxic tumour environment of various cancer models, including metastatic tumours in vivo, but can also detect a small amount of cancer cells before the formation of the tumour based on the increased oxygen consumption during cancer cell proliferation. Thus, the reported hypoxia-sensitive probe may offer an imaging tool for characterizing the tumour microenvironment in vivo, detecting cancer cells at a very early stage of tumour development and lymph node metastasis.

Nitrogen and phosphorus co-doped graphene quantum dots: synthesis from adenosine triphosphate, optical properties, and cellular imaging.

Graphene quantum dots (GQDs) are emerging zero-dimensional materials promising a wide spectrum of applications, particularly, as superior fluorescent reporters for bio-imaging and optical sensing. Heteroatom doping can endow GQDs with new or improved photoluminescence properties. Here, we demonstrate a simple strategy for the synthesis of nitrogen and phosphorus co-doped GQDs from a single biomolecule precursor (adenosine triphosphate - ATP). Such ATP-GQDs exhibit high fluorescence quantum yield, strong two-photon upconversion, small molecular weight, high photostability, and good biocompatibility. Furthermore, transferrin conjugated ATP-GQDs have been used for imaging and real-time tracking of transferrin receptors in live cells.

Development and evaluation of a non-peptidic ligand for the molecular imaging of inflammatory processes using S100A9 (MRP14) as a novel target.

The establishment of novel molecular imaging tools to monitor the local activity of inflammation remains an interdisciplinary challenge. Our target, the alarmin S100A9, one subunit of the heterodimer S100A8/S100A9 (calprotectin), is locally secreted in high concentrations from immigrated and activated phagocytes at local sites of inflammation. Calprotectin is already a well established serum biomarker for many inflammatory disorders. Here we show the development and first evaluation of the novel S100A9 specific molecular imaging probe for optical imaging of local inflammatory activity in vivo.

Gadolinium oxide nanoparticles and aptamer-functionalized silver nanoclusters-based multimodal molecular imaging nanoprobe for optical/magnetic resonance cancer cell imaging.

Multimodal molecular imaging has attracted more and more interest from researchers due to its combination of the strengths of each imaging modality. The development of specific and multifunctional molecular imaging probes is the key for this method. In this study, we fabricated an optical/magnetic resonance (MR) dual-modality molecular imaging nanoprobe, polyethylene glycol-coated ultrasmall gadolinium oxide (PEG-Gd2O3)/aptamer-Ag nanoclusters (NCs), for tracking cancer cells. To achieve this aim, PEG-Gd2O3 nanoparticles (NPs) as magnetic resonance imaging (MRI) contrast agent and aptamer functionalized silver nanoclusters (aptamer-Ag NCs) as fluorescence reporter were first synthesized by a one-pot approach, respectively. They were then conjugated by the covalent coupling reaction between the carboxyl group on the surface of PEG-Gd2O3 NPs and amino group modified on the 5'-end of AS1411 aptamer. With a suitable ratio, the fluorescence intensity of aptamer-Ag NCs and MR signal of PEG-Gd2O3 nanoparticles could both be enhanced after the formation of PEG-Gd2O3/aptamer-Ag NCs nanoprobe, which favored their application for multimodal molecular imaging. With this nanoprobe, MCF-7 tumor cells could be specifically tracked by both fluorescence imaging and magnetic resonance imaging in vitro.

Nanobubble–Affibody: Novel ultrasound contrast agents for targeted molecular ultrasound imaging of tumor

Nanobubbles (NBs), as novel ultrasound contrast agents (UCAs), have attracted increasing attention in the field of molecular ultrasound imaging for tumors. However, the preparation of uniform-sized NBs is considered to be controversial, and poor tumor selectivity in in vivo imaging has been reported. In this study, we fabricated uniform nano-sized NBs (478.2 ± 29.7 nm with polydispersity index of 0.164 ± 0.044, n = 3) using a thin-film hydration method by controlling the thickness of phospholipid films; we then conjugated the NBs with Affibody molecules to produce nano-sized UCAs referred to as NB–Affibody with specific affinity to human epidermal growth factor receptor type 2 (HER2)-overexpressing tumors. NB–Affibody presented good ultrasound enhancement, demonstrating a peak intensity of 104.5 ± 2.1 dB under ultrasound contrast scanning. Ex vivo experiments further confirmed that the NB–Affibody conjugates were capable of targeting HER2-expressing tumor cells in vivo with high affinity. The newly prepared nano-sized NB–Affibody conjugates were observed to be novel targeted UCAs for efficient and safe specific molecular imaging and may have potential applications in early cancer quantitative diagnosis and targeted therapy in the future.

Imaging of MMP Activity in Postischemic Cardiac Remodeling Using Radiolabeled MMP-2/9 Activatable Peptide Probes

The noninvasive imaging of matrix metalloproteinases (MMPs) activity in postischemic myocardial tissue holds great promise to predict cardiac function post-myocardial infarction. Consequently, development of MMP specific molecular imaging probes for noninvasive visualization and quantification of MMP activity is of great interest. A novel MMP imaging strategy is based on activatable cell-penetrating peptide probes (ACPP) that are sensitive to the proteolytic activity of MMP-2 and -9. The MMP-mediated activation of these ACPPs drives probe accumulation at the target site. The aim of this study was the development and characterization of radiolabeled MMP-2/9 sensitive ACPPs to assess MMP activity in myocardial remodeling in vivo. Specifically, a short and long-circulating MMP activatable cell-penetrating imaging probe (ACPP and Alb-ACPP, respectively; the latter is an ACPP modified with an albumin binding ligand that prolongs blood clearance) were successfully synthesized and radiolabeled. Subsequently, their biodistributions were determined in vivo in a Swiss mouse model of myocardial infarction. Both peptide probes showed a significantly higher uptake in infarcted myocardium compared to remote myocardium. The biodistribution for dual-isotope radiolabeled probes, which allowed us to discriminate between uncleaved ACPP and activated ACPP, showed increased retention of activated ACPP and activated Alb-ACPP in infarcted myocardium compared to remote myocardium. The enhanced retention correlated to gelatinase levels determined by gelatin zymography, whereas no correlation was found for the negative control: an MMP-2/9 insensitive non-ACPP. In conclusion, radiolabeled MMP sensitive ACPP probes enable to assess MMP activity in the course of remodeling post-myocardial infarction in vivo. Future research should evaluate the feasibility and the predictive value of the ACPP strategy for assessing MMP activity as a main player in postinfarction myocardial remodeling in vivo.

Circulation : Clinical Summaries

<i>Circulation</i> : Clinical Summaries

Selective Imaging of the Angiogenic Relevant Integrins α5β1 and αvβ3

Pattern seekers: For the two angiogenic relevant integrins α5β1 and αvβ3, functionalized derivatives of the selective antagonists 1 and 2 could target and discriminate between tumor cells in vivo based on their different integrin patterns and also delay tumor growth in vivo. In addition, the first α5β1-selective integrin antagonist that enables specific molecular imaging by positron emission tomography was developed.

New Development and Application of Ultrasound Targeted Microbubble Destruction in Gene Therapy and Drug Delivery

Ultrasound is a common used technique for clinical imaging. In recent years, with the advances in preparation technology of microbubbles and the innovations in ultrasound imaging, ultrasound is no longer confined to detection of tissue perfusion, but extends to specific ultrasound molecular imaging and target therapy gradually. With the development of research, ultrasound molecular imaging and target therapy have made great progresses. Targeted microbubbles for molecular imaging are achieved by binding target molecules, specific antibody or ligand to the surface of microbubbles to obtain specific imaging by attaching to target tissues. Meanwhile, it can also achieve targeting gene therapy or drug delivery by ultrasound targeted microbubble destruction (UTMD) mediating genes or drugs to specific target sites. UTMD has a number of advantages, such as target-specific, highly effective, non-invasivity, relatively low-cost and no radiation, and has broad application prospects, which is regarded as one hot spot in medical studies. We reviewed the new development and application of UTMD in gene therapy and drug delivery in this paper. With further development of technology and research, the gene or drug delivery system and related methods will be widely used in application and researches.

Imaging the Intact Mouse Cornea Using Coherent Anti-Stokes Raman scattering (CARS)

The aim of this study was to image the cellular and noncellular structures of the cornea and limbus in an intact mouse eye using the vibrational oscillation of the carbon-hydrogen bond in lipid membranes and autofluorescence as label-free contrast agents. Freshly enucleated mouse eyes were imaged using two nonlinear optical techniques: coherent anti-Stokes Raman scattering (CARS) and two-photon autofluorescence (TPAF). Sequential images were collected through the full thickness of the cornea and limbal regions. Line scans along the transverse/sagittal axes were also performed. Analysis of multiple CARS/TPAF images revealed that corneal epithelial and endothelial cells could be identified by the lipid-rich plasma membrane CARS signal. The fluorescent signal from the collagen fibers of the corneal stroma was evident in the TPAF channel. The transition from the cornea to sclera at the limbus was marked by a change in collagen pattern (TPAF channel) and thickness of surface cells (CARS channel). Regions within the corneal stroma that lack collagen autofluorescence coincided with CARS signal, indicating the presence of stromal fibroblasts or nerve fibers. The CARS technique was successful in imaging cells in the intact mouse eye, both at the surface and within corneal tissue. Multiphoton images were comparable to histologic sections. The methods described here represent a new avenue for molecular specific imaging of the mouse eye. The lack of need for tissue fixation is unique compared with traditional histology imaging techniques.

Peptide targeted tripod macrocyclic Gd(III) chelates for cancer molecular MRI

Rational design and develop of targeted contrast agents binding to cancer-related proteins will achieve more accurate cancer diagnosis and prognosis by magnetic resonance (MR) imaging. CREKA is a tumor-homing pentapeptide (Cys-Arg-Glu-Lys-Ala) specifically homes to fibrin-fibronectin complexes abundantly expressed in tumor microenvironment. In this study, we developed and evaluated a CREKA peptide targeted multiplexed Gd-MR probe (CREKA-Tris-Gd(DOTA)3) for MR imaging of breast tumors. CREKA and azide bearing Gd(III) was attached to a maleimide-functional trialkyne scaffold via thiol-maleimide and azide-alkyne click chemistry, respectively. CREKA-Tris-Gd(DOTA)3 has a well-defined structure with a molecular weight of 2914 Da. The T1 relaxivity of CREKA-Tris-Gd(DOTA)3 is 8.06 mm−1 s−1 per Gd (24.18 mm−1 s−1 per molecule) at room temperature and 3 T. Fluorescence imaging showed high binding specificity of CREKA to a 4T1 breast tumor model in mice while it was not found for the scrambled CREKA (CERAK). The CREKA peptide-targeted contrast agent resulted in greater contrast enhancement than the corresponding CERAK agent and the commercialized contrast agent ProHance® in tumor at a dose of 0.1 mmol Gd/kg in female athymic mice bearing 4T1 breast carcinoma xenograft. This small molecular contrast agent was easily excreted from body after imaging indicated low toxicity. The targeted MRI contrast agent has a potential for specific cancer molecular imaging with MRI.

An engineered anti-CA19-9 cys-diabody for positron emission tomography imaging of pancreatic cancer and targeting of polymerized liposomal nanoparticles

BackgroundAntibody-based therapeutics is a rapidly growing field. Small engineered antibody fragments demonstrate similar antigen affinity compared with the parental antibody but have a shorter serum half-life and possess the ability to be conjugated to nanoparticles. The goal of this study was to engineer an anti-carbohydrate antigen 19-9 (CA19-9) cys-diabody fragment in hopes of targeting nanoparticles to pancreatic cancer. MethodsThe anti-CA19-9 cys-diabody was created by engineering a C-terminal cysteine residue into the DNA single-chain Fv construct of the anti-CA19-9 diabody and expressed in NS0 cells. Maleimide chemistry was used to conjugate the cys-diabody to polymerized liposomal nanoparticles (PLNs) through the cysteine residues. Flow cytometry was used to evaluate targeting of cys-diabody and cys-diabody–PLN conjugate to human pancreatic cancer cell lines. The cys-diabody was radiolabeled with a positron emitter (124I) and evaluated in a mouse model of CA19-9–positive and CA19-9–negative xenografts with micro–positron emission tomography/micro–computed tomography at successive time intervals after injection. Percentage of injected dose per gram of radioactivity was measured in blood and tumor to provide objective confirmation of the micro–positron emission tomographic images. ResultsTumor xenograft imaging of the anti-CA19-9 cys-diabody demonstrated an average tumor-to-blood ratio of 3.0 and positive-to-negative tumor ratio of 7.4. Successful conjugation of the cys-diabody to PLNs was indicated by flow cytometry showing specific binding of cys-diabody–PLN conjugate to human pancreatic cancer cells in vitro. ConclusionsOur results show that the anti-CA19-9 cys-diabody targets pancreatic cancer providing specific molecular imaging in tumor xenograft models. Furthermore, the cys-diabody–PLN conjugate demonstrates target-specific binding of human pancreatic cancer cells with the potential to deliver targeted treatment.

Molecular Magnetic Resonance Imaging of Tumors with a PTPµ Targeted Contrast Agent

Molecular magnetic resonance imaging (MRI) of tumors improves the specificity of MRI by using targeted probes conjugated to contrast-generating metals. The limitation of this approach is in the identification of a target molecule present in sufficient concentration for visualization and the development of a labeling reagent that can penetrate tumor tissue with the fast kinetics required for use in a clinical setting. The receptor protein tyrosine phosphatase PTPµ is a transmembrane protein that is continuously proteolyzed in the tumor microenvironment to generate a high concentration of extracellular fragment that can be recognized by the SBK2 probe. We conjugated the SBK2 peptide to a gadolinium chelate [SBK2-Tris-(Gd-DOTA)3] to test whether the SBK2 probe could be developed as an MR molecular imaging probe. When intravenously injected into mice bearing flank tumors of human glioma cells, SBK2-Tris-(Gd-DOTA)3 labeled the tumors within 5 minutes with a high level of contrast for up to 2 hours post-injection. The contrast enhancement of SBK2-Tris-(Gd-DOTA)3 was significantly higher than that observed with a current MRI macrocyclic gadolinium chelate (Gadoteridol, ProHance) alone or a scrambled control. These results demonstrate that SBK2-Tris-(Gd-DOTA)3 labeling of the PTPµ extracellular fragment is a more specific MR molecular imaging probe than ProHance or a scrambled control. Consequently, the SBK2 probe may be more useful than the current gold standard reagent for MRI to identify tumors and to co-register tumor borders during surgical resection.

Conjugation of Antibodies to Gold Nanorods through Fc Portion: Synthesis and Molecular Specific Imaging

Anisotropic gold nanorods provide a convenient combination of properties, such as tunability of plasmon resonances and strong extinction cross sections in the near-infrared to red spectral region. These properties have created significant interest in the development of antibody conjugation methods for synthesis of targeted nanorods for a number of biomedical applications, including molecular specific imaging and therapy. Previously published conjugation approaches have achieved molecular specificity. However, the current conjugation methods have several downsides including low stability and potential cytotoxicity of bioconjugates that are produced by electrostatic interactions, as well as lack of control over antibody orientation during covalent conjugation. Here we addressed these shortcomings by introducing directional antibody conjugation to the gold nanorod surface. The directional conjugation is achieved through the carbohydrate moiety, which is located on one of the heavy chains of the Fc portion of most antibodies. The carbohydrate is oxidized under mild conditions to a hydrazide reactive aldehyde group. Then, a heterofunctional linker with hydrazide and dithiol groups is used to attach antibodies to gold nanorods. The directional conjugation approach was characterized using electron microscopy, zeta potential, and extinction spectra. We also determined spectral changes associated with nanorod aggregation; these spectral changes can be used as a convenient quality control of nanorod bioconjugates. Molecular specificity of the synthesized antibody targeted nanorods was demonstrated using hyperspectral, optical and photoacoustic imaging of cancer cell culture models. Additionally, we observed characteristic changes in optical spectra of molecular specific nanorods after their interactions with cancer cells; the observed spectral signatures can be explored for sensitive cancer detection.

Gallium-68: Chemistry and Radiolabeled Peptides Exploring Different Oncogenic Pathways

Abstract Early and specific tumor detection and also therapy selection and response evaluation are some challenges of personalized medicine. This calls for high sensitive and specific molecular imaging such as positron emission tomography (PET). The use of peptides for PET molecular imaging has undeniable advantages: possibility of targeting through peptide-receptor interaction, small size and low-molecular weight conferring good penetration in the tissue or at cellular level, low toxicity, no antigenicity, and possibility of wide choice for radiolabeling. Among β(+)-emitter radioelements, Gallium-68 is a very attractive positron-emitter compared with carbon-11 or fluorine-18 taking into account its easy production via a (68)Ge/(68)Ga generator and well established radiochemistry. Gallium-68 chemistry is based on well-defined coordination complexes with macrocycle or chelates having strong binding properties, particularly suitable for linking peptides that allow resistance to in vivo transchelation of the metal ion. Understanding specific and nonspecific molecular mechanisms involved in oncogenesis is one major key to develop new molecular imaging tools. The present review focuses on peptide signaling involved in different oncogenic pathways. This peptide signalization might be common for tumoral and non-tumoral processes or could be specific of an oncological process. This review describes gallium chemistry and different (68)Ga-radiolabeled peptides already in use or under development aiming at developing molecular PET imaging of different oncological processes.

Multiple Target-Specific Molecular Imaging Agents Detect Liver Cancer in a Preclinical Model

Liver cancer is the fifth most common cause of cancer deaths worldwide. Noninvasive diagnosis is difficult and the disease heterogeneity reduces the accuracy of pathological assays. Improvement in diagnostic imaging of specific molecular disease markers has provided hope for accurate and early noninvasive detection of liver cancer. However, all current imaging technologies, including ultrasonography, computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging, are not specific targets for detection of liver cancer. The aim of this study was to test the feasibility of injecting a cocktail of specific molecular imaging agents to noninvasively image liver cancer. The target-specific cocktail contained agents for imaging the neovasculature (RGD peptide), matrix metalloproteinase (MMP), and glucose transport (18F-fluorodeoxyglucose [18F-FDG]). Imaging studies were performed in liver cancer cells and xenograft models. The distribution of MMP at the intracellular level was imaged by confocal microscopy. RGD, MMP, and 18F-FDG were imaged on tumor-bearing mice using PET, CT, X-ray, and multi-wavelength optical imaging modalities. Image data demonstrated that each agent bound to a specific disease target component. The same liver cancer xenograft contained multiple disease markers. Those disease markers were heterogenetically distributed in the same tumor nodule. The molecular imaging agents had different distributions in the whole body and inside the tumor nodule. All target-specific agents yielded high tumor-to-background ratios after injection. In conclusion, target-specific molecular imaging agents can be used to study liver cancer in vitro and in vivo. Noninvasive multimodal/multi-target-specific molecular imaging agents could provide tools to simultaneously study multiple liver cancer components.

Translocator protein (18 kDa), a potential molecular imaging biomarker for non-invasively distinguishing non-alcoholic fatty liver disease

Mitochondrial dysfunction is responsible for liver damage and disease progression in non-alcoholic fatty liver disease (NAFLD). Translocator protein (18 kDa) (TSPO), a mitochondrial transmembrane protein, plays important roles in modulating mitochondrial function. This study explored whether TSPO can be used as an imaging biomarker of non-invasive diagnosis and staging of NAFLD, monitored using positron emission tomography (PET) with a TSPO radioligand [(18)F]FEDAC. PET with [(18)F]FEDAC, non-enhanced computerized tomography (CT), autoradiography, histopathology, and gene analysis were performed to evaluate and quantify TSPO levels and NAFLD progression in methionine and choline-deficient diet-fed mice. Correlations were analyzed between uptake ratio of radioactivity and NAFLD activity score (NAS) in the liver. Uptake of [(18)F]FEDAC obviously increased with disease progression from simple steatosis to non-alcoholic steatohepatitis (NASH) (p<0.01). A close correlation was identified between [(18)F]FEDAC uptake ratio and NAS in the liver (Pearson's r=0.922, p=0.000). Specific binding of [(18)F]FEDAC to TSPO in the NAFLD livers was assessed in competition studies with the unlabelled TSPO-selective ligand PK11195. Autoradiography and histopathology confirmed the PET imaging results. Further, the mRNA levels of the functional macromolecular signaling complex composed of TSPO were obviously higher compared to controls. TSPO expression increases in NAFLD and closely correlates with NAFLD progression. TSPO as a specific molecular imaging biomarker may open a novel avenue for non-invasive, reliable, and quantitative diagnosis and staging of NAFLD.

Abstract 2904: EGFR-targeted gold liposome for molecular imaging and therapy on NSCLC cells

Abstract Nanotechnologies are in development for monitoring drug delivery and therapeutic effect for cancer. However, tumor-targeted multifunctional nanoparticles for imaging of and therapy of lung cancer are not available. The Epidermal growth factor receptor (EGFR) is overexpressed in approximately 80% of non-small cell lung cancer (NSCLC) and is a target for novel therapeutics, however, the clinical results using EGFR inhibitors for NSCLC treatment had mixed results. These results indicate that EGFR expression or its mutational status is solely not a reliable marker to determine the outcome. Therefore, we have developed liposome (120nm) encapsulated with colloidal gold that are conjugated to therapeutic anti-EGFR antibodies (Katayama Chemical Industries Co. Ltd. Osaka, Japan) to determine the molecular specific imaging of NSCLC. The colloidal gold is used for optical imaging and the anti-EGFR antibody for therapy. In the present study, we investigated in vitro effect of these liposomes on EGFR-expressing (HCC827 and H1299) and EGFR-null (H520) NSCLC cells. EGFR-targeted liposome exhibited a strong antitumor effect on EGFR-expressing NSCLC cells. On the other hands, no significant growth inhibitory effects were observed on non-targeted liposome-treated cells. Intriguingly, treatment with EGFR-targeted liposome resulted in significantly higher cell death as compared with anti-EGFR antibody and liposome alone. Furthermore, reflected polarizing microscopy showed that the concentration of EGFR-targeted liposome bound to EGFR-expressing NSCLC cells increased, but EGFR-null cells did not. When EGFR was inhibited pharmacologically, the binding efficiency of EGFR-targeted liposome was attenuated on EGFR-expressing NSCLC cells. These findings indicate that EGFR-targeted liposome are selectively bound and delivered to EGFR expressing NSCLC cells but not the EGFR-null NSCLC cells. We are currently determining in vivo effect of EGFR-targeted liposome using subcutaneous HCC827 and H520 tumor models. Our findings demonstrated that EGFR-targeted liposome is a promising agent for therapy and molecular imaging of NSCLC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2904. doi:1538-7445.AM2012-2904

Abstract SY13-03: Molecular imaging for advanced practice in oncology

Abstract Positron Emission Tomography (PET) with 2-flouro-2-D-oxyglucose (FDG) has been the poster child for MI and several million studies are performed for oncology indications in the US alone. FDG takes advantage of the Warburg effect, which is the aerobic glycolysis that is a common feature of many malignant tumors. The incorporation of high resolution CT into the same gantry with a high resolution PET scanner, has given a further boost to PET imaging of tumors and in fact, PET CT is the most rapidly growing clinical imaging modality in the US today. Tumors for which staging, monitoring treatment response are common place include, Lung, Lymphoma, Thyroid, head and neck, melanoma, colorectal cancers. But MI with PET/CT is potentially much more than FDG PET imaging, and several 100 tracers for specific molecular imaging have been developed in the last decade. Examples include amino acid tracers, like F-18 FACBC, nucleoside analogs, like F-18 FLT, and Na 124I to imaging iodide metabolism, Androgen receptor imaging (AR) with F-18 FDHT, and Estrogen receptor imaging with F-18 FES. In addition to small molecules, positron emitting tracers like 124I-, 68 Ga and 89 Zr are widely used for radiolabeling of antibodies and peptides, opening the entire universe of ligand receptor binding for human tumors. Radiolabeled drugs are being developed and examples include F-18 desatinib, a src family tyrosine kinase inhibitor and 124I-PUH71, a heat-shock protein 90 inhibitor. These radiolabeled drugs should facilitate the study of intratumoral pharmacology of human cancers. In addition radiolabeled nanoparticles are being developed and promise specialized targeting properties, and to serve as carriers for drugs to improve therapeutic index. In summary, MI with PET is rapidly evolving as a major frontier for development of the knowledge of tumor biology and pharmacology needed to optimize treatment of the individual oncology patient. References Schoder H, Grimm J and Larson SM: Molecular Imaging Section 6 in DeVita VT Lawrence TS and Rosenberg SA: Cancer Principles and Practice of Oncology 8th Edition Volume 1 p 746 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY13-03. doi:1538-7445.AM2012-SY13-03

A radiolabeled nonapeptide probe targeting PC‐3 cells and bone metastases of prostate cancer in mice

Previous investigations showed that interleukin-11 (IL-11) and the IL-11 receptor (IL-11R) are correlated with regulation of tumor progression and may play significant roles in bone metastases. The nonapeptide structure c(CGRRAGGSC) is a phage-display-selected IL-11 mimic that binds to IL-11R. The aim of this study was to synthesize radiolabeled c(CGRRAGGSC) and to investigate the possible interaction between this radioactive probe and an IL-11R-positive bone metastasis model of PC-3 prostate cancer. The molecular probe (99m)Tc-DTPA-c(CGRRAGGSC) was radiolabeled with (99m)Tc using the diethylenetriaminepentaacetic acid (DTPA) chelate. Counterstaining was performed with LSS670, a near-infrared dye. The binding sites of the molecular probe in PC-3 cells were observed under a fluorescence microscope. The binding characteristics of the labeled probe were analyzed using radioreceptor analysis. Single photon emission tomography imaging and biodistribution of the probe were investigated using xenografts of PC-3 cells into tibias of nude mice. The labeled product, (99m) Tc-DTPA-c(CGRRAGGSC), was obtained with high labeling efficiency, high radiochemical purity and good stability. The molecular probe was combined with the PC-3 cell membrane and cytoplasm through fluorescence tracing. In the saturation and competitive inhibition experiments performed in vitro, the K(d) value was 0.32 ± 0.02 n m and the B(max) value was 754 ± 34 fmol mg(-1) pro. The probe exhibited a high tumor uptake in vivo. The radioactive molecular probe (99m) Tc-DTPA-c(CGRRAGGSC) may be used as a specific molecular imaging agent for detecting IL-11R overexpression in tumors and bone metastasis, such as prostate cancers.