Tumor Molecular Imaging Research Articles

Folic acid-cysteamine modified gold nanoparticle as a nanoprobe for targeted computed tomography imaging of cancer cells

Development of various cost-effective multifunctional nanoprobes for efficient targeted molecular imaging of tumors remains a great challenge in medicine. Herein, we report a simple method of forming folic acid-targeted multifunctional gold nanoparticles via cost-effective cysteamine as a template for tumor molecular computed tomography (CT) imaging technique. The formed multifunctional cysteamine-folic acid conjugated gold nanoparticles (FA-Cys-AuNPs) were characterized via different techniques. Colony assay, hematoxylin and eosin (H&E), MTT, and flow cytometry analysis were used to evaluate the cytocompatibility of the particles. We showed that the formed FA-Cys-AuNPs with an Au core size of ~15 nm are non-cytotoxic in a given concentration range and revealed greater X-ray attenuation intensity than iodine-based contrast agent under the same concentration of the active element. At 80 kVp, FA-Cys-AuNPs enable 1.77–times greater contrast per unit mass compared with iodine at a concentration of 2000 μg/ml, and importantly, the developed FA-Cys-AuNPs can be used as a contrast media for targeted CT imaging of folic acid receptor-expressing cancer cells in vitro. CT values of the targeted cells were 2-times higher than that of non-targeted cells at 80 kVp. These findings propose that the designed FA-Cys-AuNPs can be used as a promising contrast agent for molecular CT imaging. This data can be also considered for the application of gold nanostructures in radiation dose enhancement where nanoparticles with high X-ray attenuation are applied.

Molecular Imaging of Cancer Using X-ray Computed Tomography with Protease Targeted Iodinated Activity-Based Probes.

X-ray computed tomography (CT) is a robust, precise, fast, and reliable imaging method that enables excellent spatial resolution and quantification of contrast agents throughout the body. However, CT is largely inadequate for molecular imaging applications due mainly to its low contrast sensitivity that forces the use of large concentrations of contrast agents for detection. To overcome this limitation, we generated a new class of iodinated nanoscale activity-based probes (IN-ABPs) that sufficiently accumulates at the target site by covalently binding cysteine cathepsins that are exceptionally highly expressed in cancer. The IN-ABPs are comprised of a short targeting peptide selective to specific cathepsins, an electrophilic moiety that allows activity-dependent covalent binding, and tags containing dendrimers with up to 48 iodine atoms. IN-ABPs selectively bind and inhibit activity of recombinant and intracellular cathepsin B, L, and S. We compared the in vivo kinetics, biodistribution, and tumor accumulation of IN-ABPs bearing 18 and 48 iodine atoms each, and their control counterparts lacking the targeting moiety. Here we show that although both IN-ABPs bind specifically to cathepsins within the tumor and produce detectable CT contrast, the 48-iodine bearing IN-ABP was found to be optimal with signals over 2.1-fold higher than its nontargeted counterpart. In conclusion, this study shows the synthetic feasibility and potential utility of IN-ABPs as potent contrast agents that enable molecular imaging of tumors using CT.

Correction to: Characterization of the first fully human anti-TEM1 scFv in models of solid tumor imaging and immunotoxin-based therapy.

Tumor endothelial marker 1 (TEM1) has been identified as a novel surface marker upregulated on the blood vessels and stroma in many solid tumors. We previously isolated a novel single-chain variable fragment (scFv) 78 against TEM1 from a yeast display scFv library. Here we evaluated the potential applications of scFv78 as a tool for tumor molecular imaging, immunotoxin-based therapy and nanotherapy. Epitope mapping, three-dimensional (3D) structure docking and affinity measurements indicated that scFv78 could bind to both human and murine TEM1, with equivalent affinity, at a well-conserved conformational epitope. The rapid internalization of scFv78 and scFv78-labeled nanoparticles was triggered after specific TEM1 binding. The scFv78-saporin immunoconjugate also exerted dose-dependent cytotoxicity with high specificity to TEM1-positive cells in vitro. Finally, specific and sensitive tumor localization of scFv78 was confirmed with optical imaging in a mouse tumor model that has highly endogenous mTEM1 expression in the vasculature. Our data indicate that scFv78, the first fully human anti-TEM1 recombinant antibody, recognizes both human and mouse TEM1 and has unique and favorable features that are advantageous for the development of imaging probes or antibody-toxin conjugates for a large spectrum of human TEM1-positive solid tumors.

The state of the art of tumor molecular imaging targeting PD-1/PD-L1 pathway

Programmed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) pathway has emerged as a critical target for cancer immunotherapy, and monoclonal antibodies that block either side of this inhibitory interaction have demonstrated impressive activity across a broad set of cancer subtypes. Clinical studies have shown that tumor PD-L1 expression is associated with clinical stages and poor prognosis. Tumor PD-L1 expression detection may help to screen the patients who are most likely to be benefit from anti-PD-1/PD-L1 therapy and evaluate the prognosis. Molecular imaging technology such as PET, SPECT and optical imaging may be the modalities that allowing for noninvasively dynamic detection and overall evaluation of multiple biomarkers. This review focuses on the state of the art of tumor molecular imaging targeting PD-1/PD-L1 pathway. Key words: Neoplasms; Programmed cell death 1 receptor; Antigens, CD274; Molecular imaging; Trends

Blood-based biomarkers for precision medicine in lung cancer: precision radiation therapy.

Both tumors and patients are complex and models that determine survival and toxicity of radiotherapy or any other treatment ideally must take into account this variability as well as its dynamic state. The genetic features of the tumor and the host, and increasingly also the epi-genetic and proteomic characteristics, are being unraveled. Multiple techniques, including histological examination, blood sampling, measurement of circulating tumor cells (CTCs), and functional and molecular imaging, can be used for this purpose. However, the effects of radiation on the tumor and on organs at risk (OARs) are also influenced by the applied dose and volume of irradiated tissues. Combining all these biological, clinical, imaging, and dosimetric parameters in a validated prognostic or predictive model poses a major challenge. Here we aimed to provide an objective review of the potential of blood markers to guide high precision radiation therapy. A combined biological-mathematical approach opens new doors beyond prognostication of patients, as it allows truly precise oncological treatment. Indeed, the core for individualized and precision medicine is not only selection of patients, but even more the optimization of the therapeutic window on an individual basis. A holistic model will allow for determination of an individual dose-response relationship for each organ at risk for each tumor in each individual patient for the complete oncological treatment package. This includes, but is not limited to, radiotherapy alone. Individualized dose-response curves will allow for consideration of different doses of radiation and combinations with other drugs to plan for both optimal toxicity and complete response. Insights into the interactions between a multitude of parameters will lead to the discovery of new pathways and networks that will fuel new biological research on target discovery.

Construction of ultrasonic nanobubbles carrying CAIX polypeptides to target carcinoma cells derived from various organs

BackgroundUltrasound molecular imaging is a novel diagnostic approach for tumors, whose key link is the construction of targeted ultrasound contrast agents. However, available targeted ultrasound contrast agents for molecular imaging of tumors are only achieving imaging in blood pool or one type tumor. No targeted ultrasound contrast agents have realized targeted ultrasound molecular imaging of tumor parenchymal cells in a variety of solid tumors so far. Carbonic anhydrase IX (CAIX) is highly expressed on cell membranes of various malignant solid tumors, so it’s a good target for ultrasound molecular imaging. Here, targeted nanobubbles carrying CAIX polypeptides for targeted binding to a variety of malignant tumors were constructed, and targeted binding ability and ultrasound imaging effect in different types of tumors were evaluated.ResultsThe mean diameter of lipid targeted nanobubbles was (503.7 ± 78.47) nm, and the polypeptides evenly distributed on the surfaces of targeted nanobubbles, which possessed the advantages of homogenous particle size, high stability, and good safety. Targeted nanobubbles could gather around CAIX-positive cells (786-O and Hela cells), while they cannot gather around CAIX-negative cells (BxPC-3 cells) in vitro, and the affinity of targeted nanobubbles to CAIX-positive cells were significantly higher than that to CAIX-negative cells (P < 0.05). Peak intensity and duration time of targeted nanobubbles and blank nanobubbles were different in CAIX-positive transplanted tumor tissues in vivo (P < 0.05). Moreover, targeted nanobubbles in CAIX-positive transplanted tumor tissues produced higher peak intensity and longer duration time than those in CAIX-negative transplanted tumor tissues (P < 0.05). Finally, immunofluorescence not only confirmed targeted nanobubbles could pass through blood vessels to enter in tumor tissue spaces, but also clarified imaging differences of targeted nanobubbles in different types of transplanted tumor tissues.ConclusionsTargeted nanobubbles carrying CAIX polypeptides can specifically enhance ultrasound imaging in CAIX-positive transplanted tumor tissues and could potentially be used in early diagnosis of a variety of solid tumors derived from various organs.

Preparation and biological evaluation of 99mTc-HYNIC-(Ser)3-D4 peptide for targeting and imaging of non-small-cell lung cancer.

In this study, radiolabeled D4 peptide conjugate was studied as a radiotracer for imaging of non-small-cell lung cancer with overexpression of EGFR. HYNIC-(Ser)3-D4 peptide was labeled with 99mTc using tricine as a co-ligand. Cellular specific binding and internalization as well as in vivo tumor targeting were assessed. The in vitro experiments showed good cellular specific binding. Tumor uptake values as %ID/g were 7.55 and 6.82% at 1 and 4 h after injection, respectively. The presaturation of EGFR in xenografted nude mice reduced 36% tumor uptake of radioactivity at 1 h after injection that confirmed in vivo specificity. Findings showed this radiolabeled peptide is a promising candidate for tumor targeting and molecular imaging of non-small-cell lung cancer.

Erratum to: Gold nanoflowers for 3D volumetric molecular imaging of tumors by photoacoustic tomography

Erratum to: Gold nanoflowers for 3D volumetric molecular imaging of tumors by photoacoustic tomography

A patient-derived-xenograft platform to study BRCA-deficient ovarian cancers.

Approximately 50% of high-grade serous ovarian cancers (HGSOCs) have defects in genes involved in homologous recombination (HR) (i.e., BRCA1/2). Preclinical models to optimize therapeutic strategies for HR-deficient (HRD) HGSOC are lacking. We developed a preclinical platform for HRD HGSOCs that includes primary tumor cultures, patient-derived xenografts (PDXs), and molecular imaging. Models were characterized by immunohistochemistry, targeted sequencing, and reverse-phase protein array analysis. We also tested PDX tumor response to PARP, CHK1, and ATR inhibitors. Fourteen orthotopic HGSOC PDX models with BRCA mutations (BRCAMUT) were established with a 93% success rate. The orthotopic PDX model emulates the natural progression of HGSOC, including development of a primary ovarian tumor and metastasis to abdominal viscera. PDX response to standard chemotherapy correlated to that demonstrated in the patient. Pathogenic mutations and HGSOC markers were preserved after multiple mouse passages, indicating retention of underlying molecular mechanisms of carcinogenesis. A BRCA2MUT PDX with high p-CHK1 demonstrated a similar delay of tumor growth in response to PARP, CHK1, and ATR inhibitors. A poly (ADP-ribose) polymerase (PARP) inhibitor radiotracer correlated with PARP1 activity and showed response to PARP inhibition in the BRCA2MUT PDX model. In summary, the orthotopic HGSOC PDX represents a robust and reliable model to optimize therapeutic strategies for BRCAMUT HGSOC.

Low-intensity focused ultrasound (LIFU)-induced acoustic droplet vaporization in phase-transition perfluoropentane nanodroplets modified by folate for ultrasound molecular imaging.

The commonly used ultrasound (US) molecular probes, such as targeted microbubbles and perfluorocarbon emulsions, present a number of inherent problems including the conflict between US visualization and particle penetration. This study describes the successful fabrication of phase changeable folate-targeted perfluoropentane nanodroplets (termed FA-NDs), a novel US molecular probe for tumor molecular imaging with US. Notably, these FA-NDs can be triggered by low-intensity focused US (LIFU) sonication, providing excellent US enhancement in B-mode and contrast-enhanced US mode in vitro. After intravenous administration into nude mice bearing SKOV3 ovarian carcinomas, 1,1′-dioctadecyl-3,3,3′,3′ -tetramethylindotricarbocya-nine iodide-labeled FA-NDs were found to accumulate in the tumor region. FA-NDs injection followed by LIFU sonication exhibited remarkable US contrast enhancement in the tumor region. In conclusion, combining our elaborately developed FA-NDs with LIFU sonication provides a potential protocol for US molecular imaging in folate receptor-overexpressing tumors.

Characterization of the first fully human anti-TEM1 scFv in models of solid tumor imaging and immunotoxin-based therapy.

Tumor endothelial marker 1 (TEM1) has been identified as a novel surface marker upregulated on the blood vessels and stroma in many solid tumors. We previously isolated a novel single-chain variable fragment (scFv) 78 against TEM1 from a yeast display scFv library. Here, we evaluated the potential applications of scFv78 as a tool for tumor molecular imaging, immunotoxin-based therapy and nanotherapy. Epitope mapping, three-dimensional structure docking and affinity measurements indicated that scFv78 could bind to both human and murine TEM1, with equivalent affinity, at a well-conserved conformational epitope. The rapid internalization of scFv78 and scFv78-labeled nanoparticles was triggered after specific TEM1 binding. The scFv78-saporin immunoconjugate also exerted dose-dependent cytotoxicity with high specificity to TEM1-positive cells in vitro. Finally, specific and sensitive tumor localization of scFv78 was confirmed with optical imaging in a tumor mouse model that has highly endogenous mTEM1 expression in the vasculature. Our data indicated that scFv78, the first fully human anti-TEM1 recombinant antibody, recognizes both human and mouse TEM1 and has unique and favorable features that are advantageous for the development of imaging probes or antibody-toxin conjugates for a large spectrum of human TEM1-positive solid tumors.

Aptamers as molecular probes in tumor molecular imaging

The ideal molecular imaging probe should have characteristics of specificity, sensitivity and safety. Aptamers are sing-strand DNA or RNA oligonucleotides which can bind their targets with high specificity and high affinity. Aptamers are new types of molecular imaging probe because they have many advantages, such as their large sum of possible targets, small molecule weights, easily production and modification, low immunogenicity, high tissue penetration and so on. Now more and more aptamers research on tumor molecular imaging provides a new technology and tool for tumor diagnosis and therapy. Key words: Molecular probes; Aptamers, nucleotide; Neoplasms

Glucosamine and N-acetyl glucosamine as new CEST MRI agents for molecular imaging of tumors.

The efficacy of glucosamine (GlcN) and N-acetyl glucosamine (GlcNAc) as agents for chemical exchange saturation transfer (CEST) magnetic resonance molecular imaging of tumors is demonstrated. Both agents reflect the metabolic activity and malignancy of the tumors. The method was tested in two types of tumors implanted orthotopically in mice: 4T1 (mouse mammary cancer cells) and MCF7 (human mammary cancer cells). 4T1 is a more aggressive type of tumor than MCF7 and exhibited a larger CEST effect. Two methods of administration of the agents, intravenous (IV) and oral (PO), gave similar results. The CEST MRI observation of lung metastasis was confirmed by histology. The potential of the clinical application of CEST MRI with these agents for cancer diagnosis is strengthened by their lack of toxicity as can be indicated from their wide use as food supplements.

Abstract 4212: Molecular imaging of EGFR-expressing tumors with novel targeted protein scaffold, anti-EGFR repebody

Abstract Repebody is a binding scaffold based on variable lymphocyte receptors which are nonimmunoglobulin antibodies composed of leucine-rich repeat modules in jawless vertebrates. Repebody can be developed against variety of epitopes by module engineering. In this study, EGFR-specific repebody (RBEGFR) was developed to visualize the status of receptor expression and to prevent ligand binding that may inhibit autophosphorylation and downstream intracellular signaling. We developed RBEGFR by phage display. H1650, HCC827, A549 (human non-small cell lung cancer) and HT29 (human colon cancer) were selected as EGFR expressing cell lines. MDA-MB-435 (human melanoma) and SW620 (human colon cancer) was selected as a negative control. Specific binding of RBEGFR to cells and cancer tissue was determined by immunofluorescence (IF) staining and/or FACS analysis. In vivo imaging was done by i.v. injection of FNR-675 labeled RBEGFR (30 μg/mouse) or 64Cu-NOTA- RBEGFR (7.4 MBq/mouse) in H1650, HCC827 and HT29-bearing mouse models using cooled CCD camera or microPET, respectively. Orthotopic colon cancer mice were generated by i.p. injection of Azoxymethane (AOM; 10 mg/kg) and oral administration of 2% dextran sulfate sodium (DSS). In vivo imaging was done by i.v. injection FNR-675 labeled RBEGFR (30 μg/mouse) in AOM/DSS mouse models using cooled CCD camera or fluorescence microendoscopy. In vitro and in vivo IF staining demonstrated that strong binding of RBEGFR to H1650, HCC827 and HT29, but not to MDA-MB-435 and SW620. In vivo near infrared (NIR) imaging demonstrated specific targeting of FNR-675-RBEGFR to grafted H1650, HCC827 and HT29 tumor in mice. The 64Cu-NOTA- RBEGFR was detected at the implanted tumor from 1 h (SUVmax: 1.34±0.12) after the injection, peaked at 6 h (1.75±0.18), maintained to 24 h (1.33±0.17). The radioactivity significantly decreased by blocking with cold form of 50 μM naïve RBEGFR 1 day before injection of 64Cu-NOTA- RBEGFR, indicating specific binding of RBEGFR to EGFR in vivo. Optical NIR imaging after i.v. injection of FNR-675-RBEGFR showed specific signal in the abdomen of AOM/DSS mice, but not in control mice. Correlation with surgical/necropsy imaging, fluorescence endoscopy and pathology revealed strong accumulation of FNR-675-RBEGFR in malignant dysplasia, but weak or no accumulation in low grade tumor or benign lesion. In conclusion, the RBEGFR could be developed for specific targeting of cancer overexpressing EGFR. The fluorescence-labeled RBEGFR could be developed for imaging agent for detecting colonic dysplasia and assessing EGFR status. In particular, this agent may have a potential as an imaging companion diagnostics to predict therapeutic outcome of targeted therapy with monoclonal antibody for EGFR through pre-therapeutic visualization of EGFR status. Our work provides a basis to develop potential strategy of targeted immune-detection of cancers which may replace monoclonal antibodies. Citation Format: Misun Yun, Dong-Yeon Kim, Hyeon-Sik Kim, Jin Hai Zheng, AYoung Pyo, Jung-Joon Min. Molecular imaging of EGFR-expressing tumors with novel targeted protein scaffold, anti-EGFR repebody. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4212.

MR molecular imaging of tumors based on an optimal hTERT promoter tyrosinase expression system

The early diagnosis and treatment of tumors is of vital significance to increase patient survival. Therefore, we constructed a lentiviral vector expressing tyrosinase (TYR) driven by an optimized human telomerase reverse transcriptase (hTERT) promoter or a cytomegalovirus(CMV) promoter in the hopes of performing noninvasive and real-time tumor-specific imaging. First, hTERT-TYR and CMV-TYR were constructed to infect cancer cell lines (telomerase-negative cell line: U2OS; telomerase-positive cell lines: SGC-7901, SW480 and HepG2). Subsequently, stable tyrosinase-expressing cell lines were sorted by flow cytometry out of these infected cancer cell lines. Then, the mRNA and protein levels of tyrosinase were analyzed. Thetyrosinase activity, melanin production and ferric ion adsorption were measured followed by an MR scan. Consequently the results showed that tyrosinase was only expressed in telomerase-positive tumor cells infected by hTERT-TYR, whereas tyrosinase was expressed in both telomerase-negative and telomerase-positive tumor cells infected by CMV-TYR. Finally, we performed in vivo tumor MR using a clinical 3T MR scanner and found increased signals at T1W1 from telomerase-positive cells infected by hTERT-TYR, which revealed that MR scanning could distinguish cells with hTERT -positive cells from hTERT-negative cells infected with the optimized lentivirus. The mechanism underlying this effect is that tyrosinase promotes melanin production and ferric ion adsorption only in hTERT-expressing cells. Taken together, these data show that this optimized hTERT promoter-driving tyrosinase expression system might be a useful diagnostic tool for the detection of tumors using MR imaging.

Tumor Molecular Imaging with Nanoparticles

ABSTRACT Molecular imaging (MI) can provide not only structural images using traditional imaging techniques but also functional and molecular information using many newly emerging imaging techniques. Over the past decade, the utilization of nanotechnology in MI has exhibited many significant advantages and provided new opportunities for the imaging of living subjects. It is expected that multimodality nanoparticles (NPs) can lead to precise assessment of tumor biology and the tumor microenvironment. This review addresses topics related to engineered NPs and summarizes the recent applications of these nanoconstructs in cancer optical imaging, ultrasound, photoacoustic imaging, magnetic resonance imaging (MRI), and radionuclide imaging. Key challenges involved in the translation of NPs to the clinic are discussed.

High Resolution Molecular Radiation Therapy and Tumor Imaging for the 21st Century

With the lightest ions beyond protons, i.e., Helium, Lithium and Beryllium ions, highly specific Molecular Bragg peak radiation therapy of malignant tumors is possible with minimal adverse normal tissue reactions elsewhere in the body. The Bragg peak ionization density is only elevated in a few mm wide spot at the end of the ion range with resultant increased local apoptosis and senescence. By only placing Bragg peaks in the tumor, an increased local therapeutic effect is obtained with only low ionization density and easily repairable damage in surrounding normal tissues. A geometrical accuracy in dose delivery of about 1 mm is possible with these ions, and high-resolution molecular tumor imaging is then needed to accurately delineate the target volume. It is proposed that ultra-sensitivity whole body PET cameras should be built to achieve mm resolution in the whole target region. With about 1 m axial field of view an almost 50-fold increased sensitivity and a reduced imaging time down to a few minutes should be in reach. To get sub mm resolution with whole body spectroscopic MR, about 15 Tesla to 20 Tesla is needed and will significantly increase the resolution with tumor specific metabolite imaging from the 10 mm to 15 mm available today. In the future, it should also be possible to achieve a resolution as high as 10 μm with Stereoscopic Phase Contrast X-ray imaging, or to reduce the dose and imaging time by using 2 projections instead of 400 to get 3D images, thanks to the significantly increased contrast in each projection. When these new methods are brought into clinical use together with light ion therapy a mean tumor cure as high as 80% should be possible, and even more if the new early tumor detection and malignancy estimation methods are brought into more regular clinical use.

A small-molecule dye for NIR-II imaging.

Fluorescent imaging of biological systems in the second near-infrared window (NIR-II) can probe tissue at centimetre depths and achieve micrometre-scale resolution at depths of millimetres. Unfortunately, all current NIR-II fluorophores are excreted slowly and are largely retained within the reticuloendothelial system, making clinical translation nearly impossible. Here, we report a rapidly excreted NIR-II fluorophore (∼90% excreted through the kidneys within 24 h) based on a synthetic 970-Da organic molecule (CH1055). The fluorophore outperformed indocyanine green (ICG)-a clinically approved NIR-I dye-in resolving mouse lymphatic vasculature and sentinel lymphatic mapping near a tumour. High levels of uptake of PEGylated-CH1055 dye were observed in brain tumours in mice, suggesting that the dye was detected at a depth of ∼4 mm. The CH1055 dye also allowed targeted molecular imaging of tumours in vivo when conjugated with anti-EGFR Affibody. Moreover, a superior tumour-to-background signal ratio allowed precise image-guided tumour-removal surgery.

Anticalins directed against the fibronectin extra domain B as diagnostic tracers for glioblastomas

The standard of care for diagnosis and therapy monitoring of gliomas is magnetic resonance imaging (MRI), which however, provides only an indirect and incomplete representation of the tumor mass, offers limited information for patient stratification according to WHO-grades and may insufficiently indicate tumor relapse after antiangiogenic therapy. Anticalins are alternative binding proteins obtained via combinatorial protein design from the human lipocalin scaffold that offer novel diagnostic reagents for histology and imaging applications. Here, the Anticalins N7A, N7E and N9B, which possess exquisite specificity and affinity for oncofetal fibronectin carrying the extra domain B (ED-B), a well-known proangiogenic extracellular matrix protein, were applied for immunohistochemical studies. When investigating ED-B expression in biopsies from 41 patients with confirmed gliomas of WHO grades I to IV, or in non-neoplastic brain samples, we found that Anticalins specifically detect ED-B in primary glioblastoma multiforme (GBM; WHO IV) but not in tumors of lower histopathological grade or in tumor-free brain. In primary GBM samples, ED-B specific Anticalins locate to fibronectin-rich perivascular areas that are associated with angiogenesis. Anticalins specifically detect ED-B both in fixed tumor specimen and on vital cells, as evidenced by cytofluorometry. Beyond that, we labeled an Anticalin with the γ-emitter (123) I and demonstrated specific binding to GBM-tissue samples using in vitro autoradiography. Overall, our data indicate that ED-B specific Anticalins are useful tools for the diagnosis of primary GBM and related angiogenic sites, presenting them as promising tracers for molecular tumor imaging.

Preventive Medicine using Impedimetric Biosensors: Early Detection of Cancer

human cells (5-10 μm in diameter) and can readily interact with biomolecules on both the cell surface and within the cell. These molecular level interactions provide useful information for monitoring complex cellular processes including the onset of biomolecular transformations leading towards cancer metastasis. The surface of nanoparticles can be modified with appropriate ligands to target tumor cells with high specificity and affinity and are used extensively for delivering therapeutic drugs and imaging contrast agents to the cancer cells while sparing the normal healthy cells. Surface modifications render nanoparticles biocompatible and reduce toxicity levels, which is crucial for in vivo applications. Applications of nanotechnology for cancer management involve the use of nanoparticles for detecting cancer at its earliest stages, precisely locating its position within the body, delivering anticancer drugs, specifically to malignant cells, and determining if these drugs are killing the malignant cells. Figure 1-1 summarizes the cancer nanotechnology applications through molecular tumor imaging, early detection, molecular diagnosis, targeted therapy, and bioinformatics [7]. Early detection can be achieved by monitoring the human body for certain cancer biomarkers. These biomarkers can be of various molecular origins depending on the specific cancer. (i.e., proteins, DNA/RNA) Cancer biomarkers are great tools not only for early detection ofcancer; but also monitoring the progress of a cancer treatment [4]. Received: October 04, 2015; Accepted: October 06, 2015; Published: October 09, 2015