Molecular Imaging Of Cancer Research Articles

Phosphatidylserine-Targeted Nanotheranostics for Brain Tumor Imaging and Therapeutic Potential.

Phosphatidylserine (PS), the most abundant anionic phospholipid in cell membrane, is strictly confined to the inner leaflet in normal cells. However, this PS asymmetry is found disruptive in many tumor vascular endothelial cells. We discuss the underlying mechanisms for PS asymmetry maintenance in normal cells and its loss in tumor cells. The specificity of PS exposure in tumor vasculature but not normal blood vessels may establish it a useful biomarker for cancer molecular imaging. Indeed, utilizing PS-targeting antibodies, multiple imaging probes have been developed and multimodal imaging data have shown their high tumor-selective targeting in various cancers. There is a critical need for improved diagnosis and therapy for brain tumors. We have recently established PS-targeted nanoplatforms, aiming to enhance delivery of imaging contrast agents across the blood–brain barrier to facilitate imaging of brain tumors. Advantages of using the nanodelivery system, in particular, lipid-based nanocarriers, are discussed here. We also describe our recent research interest in developing PS-targeted nanotheranostics for potential image-guided drug delivery to treat brain tumors.

Development of new PTK7-targeting aptamer-fluorescent and -radiolabelled probes for evaluation as molecular imaging agents: Lymphoma and melanoma in vivo proof of concept

Aptamers are single-stranded oligonucleotides that recognize molecular targets with high affinity and specificity. Aptamer that selectively bind to the protein tyrosine kinase-7 (PTK7) receptor, overexpressed on many cancers, has been labelled as probes for molecular imaging of cancer. Two new PTK7-targeting aptamer probes were developed by coupling frameworks from the fluorescent dye AlexaFluor647 or the 6-hydrazinonicotinamide (HYNIC) chelator-labelled to 99mTc. The derivatizations via a 5′-aminohexyl terminal linker were done at room temperature and under mild buffer conditions. Physicochemical and biological controls for both imaging agents were performed verifying the integrity of the aptamer-conjugates by HPLC. Recognition of melanoma (B16F1) and lymphoma (A20) mouse cell lines by the aptamer was studied using cell binding, flow cytometry and confocal microscopy. Finally, in vivo imaging studies in tumour-bearing mice were performed. The new probes were able to bind to melanoma and lymphoma cell lines in vitro, the in vivo imaging in tumour-bearing mice showed different uptake behaviours showing for the fluorescent conjugate good uptake by B cell lymphoma while the radiolabelled conjugate did not display tumour uptake due to its high extravascular distribution, and both showed rapid clearance properties in tumour-bearing mice.

64Cu2+ Ions as PET Probe: An Emerging Paradigm in Molecular Imaging of Cancer

Positron emission tomography (PET) imaging has transformed diagnostic nuclear medicine and become an essential strategy in cancer management. With the expected growth of this molecular imaging modality, there is a recognized need for new PET probes to address the clinical challenges in the early diagnosis and staging of various types of cancers. In this endeavor, the prospect of using 64Cu in the form of simple Cu2+ ions as PET probe is not only a cost-effective proposition but also seems poised to broaden the palette of molecular imaging probes in the foreseeable future. The usefulness of 64Cu2+ ions as PET probe is based on the fact that Cu is an essential element that plays an important role in cell proliferation and angiogenesis. Over the past few years, there has been continuous flow of evidences based on studies in animal models on the uptake of 64Cu2+ ions in different types of tumors, including, hepatoma, colorectal cancer, prostate cancer, lung cancer, breast cancer, head and neck cancer, fibrosarcoma, melanoma, glioblastoma, and ovarian cancer. The widespread preclinical success of 64Cu2+ ions as PET probe has recently resulted in translation of this radiotracer to clinical settings for noninvasive imaging and staging of prostate cancer in human patients. In this concise review, we have focused on the latest developments in PET imaging of cancer in preclinical and clinical settings using 64Cu2+ ion as a probe and discussed the challenges and opportunities for future development.

Molecular Cancer Imaging with Polymeric Nanoassemblies: From Tumor Detection to Theranostics.

Several imaging modalities have been widely applied for the detection of cancer and its pathological activity in combination with probes capable of improving the contrast between healthy and cancerous tissues. Biocompatible polymeric nanoassemblies have been developed for precise detection of malignant tumors by enhancing the selectivity and sensitivity of the imaging. Exploiting the compartmentalized structure of the nanoassemblies advantageously allows delivering both imaging and therapeutic agents for cancer multifunctional imaging and theranostics, i.e., the combination of therapy and diagnosis tool on a single platform. Thus, nanoassemblies have high potential not only for cancer molecular imaging but also for tracing nanoparticles in biological systems, studying their biological pathways, gathering pathological information, monitoring therapeutic effects, and guiding pinpoint therapies. In this review, polymeric nanoassemblies for optical imaging, magnetic resonance imaging, multifunctional imaging, and image-guided therapy, emphasizing their role in cancer diagnosis and theranostics are highlighted.

Single‐Layer MoS2 Nanosheets with Amplified Photoacoustic Effect for Highly Sensitive Photoacoustic Imaging of Orthotopic Brain Tumors

Photoacoustic (PA) imaging, as a fast growing technology that combines the high contrast of light and large penetration depth of ultrasound, has demonstrated great potential for molecular imaging of cancer. However, PA molecular imaging of orthotopic brain tumors is still challenging, partially due to the limited options and insufficient sensitivity of available PA molecular probes. Here, the direct formation of single‐layer (S‐MoS2), few‐layer (F‐MoS2), and multi‐layer (M‐MoS2) nanosheets by the albumin‐assisted exfoliation without further surface modifications is reported. It is demonstrated that the PA effect of the MoS2 nanosheets is highly dependent on their layered nanostructures. Decreasing the number of nanosheet layers from M‐MoS2 to S‐MoS2 can both significantly enhance the near‐infrared light absorption and improve the elastic properties of the nanomaterial, resulting in greatly amplified PA effect. The in vitro experiments demonstrate that the prepared S‐MoS2 with excellent biocompatibility can be efficiently internalized into U87 glioma cells, producing strong PA signals for highly sensitive detection of brain tumor cells, with a detection limit of ≈100 cells. Intravenous administration of S‐MoS2 to both U87 subcutaneous and orthotopic tumor‐bearing mice shows highly efficient tumor retention and significantly enhanced PA contrast. Tumor tissue ≈1.5 mm below the skull can still be clearly visualized in vivo. Previous studies suggest that the fabricated S‐MoS2 with amplified PA effect have high potential to serve as an efficient nanoplatform for sensitive PA molecular imaging and hold promising prospect for translational medicine.

Fab(nimotuzumab)-HYNIC-99mTc: Antibody Fragmentation for Molecular Imaging Agents.

Finally, fast blood clearance nimotuzumab is a humanized monoclonal antibody that recognise, with high specific affinity, the epidermal growth factor receptor (EGF-R) which play an important role in the growth process associated with many solid tumors. In this work, the whole antibody was digested with papain in order to generate a Fab fragment, derivatized with NHS-HYNIC-Tfa and radiolabel with technetium-99m (99mTc) as a potential agent of molecular imaging of cancer. Both, whole and fragment radiolabels were in-vivo and in-vitro characterized. Radiolabeling conditions with Tricine as coligand and quality controls were assessed to confirm the integrity of the labeled fragment. Biodistribution and imaging studies in normal and spontaneous adenocarcinoma mice were performed at different times to determine the in-vivo characteristics of the radiolabel fragment. Tumor localization was visualized by conventional gamma camera imaging studies, and the results were compared with the whole antibody. Also, an immunoreactivity assay was carried out for both. The results showed clearly the integrity of the nimotuzumab fragment and the affinity by the receptor was verified. Fab(nimotuzumab)-HYNIC was obtained with high purity and a simple strategy of radiolabeling was performed. Finally, a fast blood clearance was observed in the biodistribution studies increasing the tumor uptake of Fab(nimotuzumab)- HYNIC-99mTc over time, with tumor/muscle ratios of 3.81 ± 0.50, 5.16 ± 1.97 and 6.32 ± 1.98 at 1 h, 4 h and 24 h post injection. Urinary excretion resulted in 32.89 ± 3.91 %ID eliminated at 24 h. Scintigraphy images showed uptake in the tumor and the activity in non-target organs was consistent with the biodistribution data at the same time points. Hence, these preliminary results showed important further characteristic of Fab(nimotuzumab)-HYNIC-99mTc as a molecular imaging agent of cancer.

Current and Emerging Clinical Applications of Multispectral Optoacoustic Tomography (MSOT) in Oncology.

Accurate detection and characterization of cancers are key for providing timely intervention and effective treatments. Current imaging technologies are particularly limited when it comes to detecting very small tumors in vivo, i.e., very early cancers or metastases, differentiating viable tumor from surrounding dead tumor tissue, and evaluating tumor metabolism within tissue. Optoacoustic imaging offers potential solutions to these imaging problems because of its ability to image optical absorption properties of both intrinsic tissue chromophores and exogenous contrast agents without the involvement of ionizing radiation. Optoacoustic imaging uses pulsed laser to induce localized thermoelastic expansion that generates acoustic waves detectable by an ultrasound transducer. To date, multispectral optoacoustic tomography (MSOT) has primarily been used in preclinical research; however, its use in translational and clinical research is expanding. This review focuses on current and emerging applications of optoacoustic imaging for molecular imaging of cancer using both exogenous and endogenous contrast agents and sheds light on potential future clinical applications. Clin Cancer Res; 22(14); 3432-9. ©2016 AACR.

SPECT imaging of neuropilin receptor type-1 expression with 131I-labeled monoclonal antibody.

As a novel co-receptor for vascular endothelial growth factor (VEGF), neuropilin receptor type-1 (NRP-1) is overexpressed in several cancers and metastases, and serves as an attractive target for cancer molecular imaging and therapy. Previous single photon emission computerized tomography (SPECT) studies demonstrated that the small NRP-1-targeting peptides 99mTc-MA-ATWLPPR and 99mTc-CK3 showed poor tumor imaging quality, because of their rapid blood clearance and very low tumor uptake. Compared with small peptides, monoclonal antibodies (mAbs) can improve imaging of NRP-1-expression, due to their high affinity, specificity and slow extraction. A6-11-26 is a novel monoclonal antibody against NRP-1 b1b2 domain that exhibits inhibition of tumor growth in NPR-1-expressing preclinical models. The aim of the present study was to develop the 131I-labeled anti-NRP-1 monoclonal antibody A6-11-26 as a SPECT probe for imaging of NRP-1-positive tumor. An anti-NRP-1 monoclonal antibody (A6-11-26) was produced by hybridomas and was labeled with iodine-131 by the iodogen method. Invitro, the radiolabeling efficiency, radiochemical purity, immunoreactive fraction and stability were assessed. Binding affinity and specificity of 131I‑A6-11-26 to NRP-1 were evaluated using human glioblastoma U87MG cells. Invivo, biodistribution and SPECT/CT studies were conducted on mice bearing U87MG xenografts after the injection of 131I-A6-11-26 with or without co-injection of unlabeled A6-11-26 antibody. A6-11-26 was generated successfully by hybridoma with high purity (>95%) and was labeled with iodine-131 within 60min with high labelling efficiency (95.46±3.34%), radiochemical purity (98.23±1.41%). 131I-A6-11-26 retained its immunoreactivity and also displayed excellent stability in mouse serum and PBS solution during 1 to 96h. Cell uptake assays showed high NRP-1-specific uptake (15.80±1.30% applied activity at 6h) in U87MG cells. 131I-A6-11-26 bound to NRP-1 with low nanomolar affinity (KD=1.67±0.14nM) in U87MG cells. Invivo, biodistribution study demonstrated targeting of U87MG glioma xenografts was NRP-1 specific. The tumor uptake was 6.00±1.24%ID/g at 24h, and the tumor to muscle ratio was 3.20±0.30 at 24h, and reached the highest level of 6.13±0.24 at 120h after injection. SPECT imaging studies revealed that 131I-A6-11-26 could clearly identify U87MG tumors with good contrast, especially at 72-120h after injection. The present study demonstrates that 131I-A6-11-26 is capable of detecting lesions in an NRP-1-expressing tumor with high target selectivity, and may offer a promising SPECT agent for NRP-1 expression positive tumor and encourage further investigation.

Highlights lecture EANM 2015: the search for nuclear medicine's superheroes.

The EANM 2015 Annual Congress, held from October 10th to 14th in Hamburg, Germany, was outstanding in many respects. With 5550 participants, this was by far the largest European congress concerning nuclear medicine. More than 1750 scientific presentations were submitted, with more than 250 abstracts from young scientists, indicating that the future success of our discipline is fuelled by a high number of young individuals becoming involved in a multitude of scientific activities. Significant improvements have been made in molecular imaging of cancer, particularly in prostate cancer. PSMA-directed PET/CT appears to become a new gold standard for staging and restaging purposes. Novel tumour specific compounds have shown their potential for target identification also in other solid neoplasms and further our understanding of tumour biology and heterogeneity. In addition, a variety of nuclear imaging techniques guiding surgical interventions have been introduced. A particular focus of the congress was put on targeted, radionuclide based therapies. Novel theranostic concepts addressing also tumour entities with high incidence rates such as prostate cancer, melanoma, and lymphoma, have shown effective anti-tumour activity. Strategies have been presented to improve further already established therapeutic regimens such as somatostatin receptor based radio receptor therapy for treating advanced neuroendocrine tumours. Significant contributions were presented also in the neurosciences track. An increasing number of target structures of high interest in neurology and psychiatry are now available for PET and SPECT imaging, facilitating specific imaging of different subtypes of dementia and movement disorders as well as neuroinflammation. Major contributions in the cardiovascular track focused on further optimization of cardiac perfusion imaging by reducing radiation exposure, reducing scanning time, and improving motion correction. Besides coronary artery disease, many contributions focused on cardiac inflammation, cardiac sarcoidosis, and specific imaging of large vessel vasculitis. The physics and instrumentation track included many highlights such as novel, high resolution scanners. The most noteworthy news and developments of this meeting were summarized in the highlights lecture. Only 55 scientific contributions were mentioned, and hence they represent only a brief summary, which is outlined in this article. For a more detailed view, all presentations can be accessed by the online version of the European Journal of Nuclear Medicine and Molecular Imaging (Volume 42, Supplement 1).

The Impact Factor of Radiological Journals: Associations with Journal Content and Other Characteristics Over a Recent 12-Year Period

The aim of this study was to evaluate the trends in the impact factor (IF) of radiological journals over a recent 12-year period, including associations between IF and journal topic. Journal Citation Reports (JCR) was used to identify all biomedical journals and all radiological journals (assigned a JCR category of "Radiology, Nuclear Medicine, & Medical Imaging"), along with journal IF, in 2003 and 2014. Radiological journals were manually classified by topic. Trends in median IF (mIF) were assessed. The number of radiological journals increased from 83 (2003) to 125 (2014) (all biomedical journals: 5907 to 8718, respectively). mIF of radiological journals increased from 1.42 (2003) to 1.75 (2014) (all biomedical journals: 0.93 to 1.46, respectively). The most common topic among new radiological journals was general (nonspecialized) radiology (8). Five new radiological journals in 2014 were in topics (cancer imaging and molecular imaging) having no journals in 2003. mIF of general radiological journals was 1.49. Topics having highest mIF were cardiac imaging (2.94), optics (2.86), molecular imaging (2.77), radiation oncology (2.60), and neuroradiology (2.25). Topics with lowest mIF were ultrasound (1.19) and interventional radiology (1.44). Topics with the largest increase in mIF were cardiac imaging (from 1.17 to 2.94) and neuroradiology (from 1.07 to 2.25). Radiological journals exhibited higher mIF than biomedical journals overall. Among radiological journals, subspecialty journals had highest mIF. While a considerable number of new radiological journals since 2003 were general radiology journals having relatively low IF, there were also new journal topics representing emerging areas of subspecialized radiological research.

A targeted nanoglobular contrast agent from host-guest self-assembly for MR cancer molecular imaging

The clinical application of nanoparticular Gd(III) based contrast agents for tumor molecular MRI has been hindered by safety concerns associated with prolonged tissue retention, although they can produce strong tumor enhancement. In this study, a targeted well-defined cyclodextrin-based nanoglobular contrast agent was developed through self-assembly driven by host-guest interactions for safe and effective cancer molecular MRI. Multiple β-cyclodextrins attached POSS (polyhedral oligomeric silsesquioxane) nanoglobule was used as host molecule. Adamantane–modified macrocyclic Gd(III) contrast agent, cRGD (cyclic RGDfK peptide) targeting ligand and fluorescent probe was used as guest molecules. The targeted host-guest nanoglobular contrast agent cRGD-POSS-βCD-(DOTA-Gd) specifically bond to αvβ3 integrin in malignant 4T1 breast tumor and provided greater contrast enhancement than the corresponding non-targeted agent. The agent also provided significant fluorescence signal in tumor tissue. The histological analysis of the tumor tissue confirmed its specific and effective targeting to αvβ3 integrin. The targeted imaging agent has a potential for specific cancer molecular MR and fluorescent imaging.

Detection of early primary colorectal cancer with upconversion luminescent NP-based molecular probes.

Early detection and diagnosis of cancers is extremely beneficial for improving the survival rate of cancer patients and molecular imaging techniques are believed to be relevant for offering clinical solutions. Towards early cancer detection, we developed a primary animal colorectal cancer model and constructed a tumor-specific imaging probe by using biocompatible NaGdF4:Yb,Er@NaGdF4 upconversion luminescent NPs for establishing a sensitive early tumor imaging method. The primary animal tumor model, which can better mimic the human colorectal cancer, was built upon continual administration of 1,2-dimethylhydrazine in Kunming mice and the tumor development was carefully monitored through histopathological and immunohistochemical analyses to reveal the pathophysiological processes and molecular features of the cancer microenvironment. The upconversion imaging probe was constructed through covalent coupling of PEGylated core-shell NPs with folic acid whose receptor is highly expressed in the primary tumors. Upon 980 nm laser excitation, the primary colorectal tumors in the complex abdominal environment were sensitively imaged owing to the ultralow background of the upconversion luminescence and the high tumor-targeting specificity of the nanoprobe. We believe that the current studies provide a highly effective and potential approach for early colorectal cancer diagnosis and tumor surgical navigation.

Biodistribution of Novel 68Ga-Radiolabelled HER2 Aptamers in Mice

Background: Two novel HER2 aptamers were recently selected with great potential for the in vitro diagnosis of HER2-positive cancer. The goal of this study was to examine the in vivo diagnostic potential of these HER2 aptamers. Methods: Both HER2 aptamers were radiolabelled with 68Ga, injected in mice bearing a HER2-positive and HER2-negative tumour and evaluated by PET/MRI. Results: Ex vivo bio distribution analysis revealed high uptake in the blood, tissues and organs, except the brain. Interestingly, this high uptake was explained by the slow blood clearance due to non-specific aptamer binding to blood proteins. We observed accumulation of radioactivity in both tumours in time. Although higher uptake in the HER2-positive tumour compared to the HER2-negative tumour was observed, this was accompanied with more necrosis in the HER2-negative tumour, which was observed by 18FDG PET/CT. Conclusion: This work presents a first step towards the development of 68Ga-labelled aptamers for molecular cancer imaging.

Molecular imaging and therapy targeting copper metabolism in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC. Copper is a nutritional metal required for the function of numerous enzymatic molecules in the metabolic pathways of human cells. Emerging evidence suggests that copper plays a role in cell proliferation and angiogenesis. Increased accumulation of copper ions was detected in tissue samples of HCC and many other cancers in humans. Altered copper metabolism is a new biomarker for molecular cancer imaging with position emission tomography (PET) using radioactive copper as a tracer. It has been reported that extrahepatic mouse hepatoma or HCC xenografts can be localized with PET using copper-64 chloride as a tracer, suggesting that copper metabolism is a new biomarker for the detection of HCC metastasis in areas of low physiological copper uptake. In addition to copper modulation therapy with copper chelators, short-interference RNA specific for human copper transporter 1 (hCtr1) may be used to suppress growth of HCC by blocking increased copper uptake mediated by hCtr1. Furthermore, altered copper metabolism is a promising target for radionuclide therapy of HCC using therapeutic copper radionuclides. Copper metabolism has potential as a new theranostic biomarker for molecular imaging as well as targeted therapy of HCC.

Cutting Edge of Cancer Molecular Imaging Technology and Beyond

Cutting Edge of Cancer Molecular Imaging Technology and Beyond

Screening and Identification of a Phage Display Derived Peptide That Specifically Binds to the CD44 Protein Region Encoded by Variable Exons

CD44, especially the isoforms with variable exons (CD44v), is a promising biomarker for the detection of cancer. To develop a CD44v-specific probe, we screened a 7-mer phage peptide library against the CD44v3-v10 protein using an improved subtractive method. The consensus sequences with the highest frequency (designated CV-1) emerged after four rounds of panning. The binding affinity and specificity of the CV-1 phage and the synthesized peptide for the region of CD44 encoded by the variable exons were confirmed using enzyme-linked immunosorbent assay and competitive inhibition assays. Furthermore, the binding of the CV-1 probe to gastric cancer cells and tissues was validated using immunofluorescence and immunohistochemistry assays. CV-1 sensitively and specifically bound to CD44v on cancer cells and tissues. Thus, CV-1 has the potential to serve as a promising probe for cancer molecular imaging and target therapy.

Theragnosis-based combined cancer therapy using doxorubicin-conjugated microRNA-221 molecular beacon

Recently, microRNA (miRNA or miR) has emerged as a new cancer biomarker because of its high expression level in various cancer types and its role in the control of tumor suppressor genes. In cancer studies, molecular imaging and treatment based on target cancer markers have been combined to facilitate simultaneous cancer diagnosis and therapy. In this study, for combined therapy with diagnosis of cancer, we developed a doxorubicin-conjugated miR-221 molecular beacon (miR-221 DOXO MB) in a single platform composed of three different nucleotides: miR-221 binding sequence, black hole quencher 1 (BHQ1), and doxorubicin binding site. Imaging of endogenous miR-221 was achieved by specific hybridization between miR-221 and the miR-221 binding site in miR-221 DOXO MB. The presence of miR-221 triggered detachment of the quencher oligo and subsequent activation of a fluorescent signal of miR-221 DOXO MB. Simultaneous cancer therapy in C6 astrocytoma cells and nude mice was achieved by inhibition of miRNA-221 function that downregulates tumor suppressor genes. The detection of miR-221 expression and inhibition of miR-221 function by miR-221 DOXO MB provide the feasibility as a cancer theragnostic probe. Furthermore, a cytotoxic effect was induced by unloading of doxorubicin intercalated into miR-221 DOXO MB inside cells. Loss of miR-221 function and cytotoxicity induced by the miR-221 DOXO MB provides combined therapeutic efficacy against cancers. This method could be used as a new theragnostic probe with enhanced therapy to detect and inhibit many cancer-related miRNAs.

Clinical roles of breast 3T MRI, FDG PET/CT, and breast ultrasound for asymptomatic women with an abnormal screening mammogram

BackgroundMagnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) show promise for molecular cancer imaging. We evaluated 3T MRI, FDG PET/CT, and ultrasound images for asymptomatic women with an abnormal screening mammogram. MethodsThe Institutional Review Board of Kaohsiung Veterans General Hospital (Kaohsiung, Taiwan) approved the study. Patients provided written informed consent. A total of 11,865 screening mammograms of 118,65 women were performed at our facility between January 2011 and December 2012. Fifty-three asymptomatic women (mean age, 53.3 years) whose screening mammograms had a Breast Imaging Reporting and Data System (BI-RADS) category of 4 or 5 were ultimately enrolled in this study. Breast 3T MRI, FDG PET/CT, and breast ultrasound were performed before biopsy. All imaging modalities were compared by lesion-by-lesion analyses. ResultsFifty-nine breast lesions (28 malignant and 31 benign lesions) from 53 women were analyzed. The sensitivity, specificity, and accuracy for 28 breast cancers were 96%, 77%, and 86%, respectively, for breast 3T MRI; 50%, 100%, and 76%, respectively, for FDG PET,CT; and 61%, 87%, and 74%, respectively, for breast ultrasound. One 0.8-cm invasive breast cancer was missed by the screening mammogram, but detected by breast 3T MRI and FDG PET/CT. The sensitivity for detecting breast cancer was significantly higher with MRI than with PET/CT or ultrasound (for all, p < 0.01). The specificity for detecting breast cancer was significantly higher for PET/CT than for breast MRI (p = 0.02). The sensitivity exhibited by 3T breast MRI and FDG PET/CT for 16 noninvasive breast cancers was 94% and 25%, respectively. ConclusionOn screening mammograms, breast 3T MRI showed higher sensitivity but less specificity than FDG PET/CT for detecting asymptomatic breast cancers.

Direct-Conversion Molecular Breast Imaging of Invasive Breast Cancer: Imaging Features, Extent of Invasive Disease, and Comparison Between Invasive Ductal and Lobular Histology.

The purposes of this study were to compare the tumor appearance of invasive breast cancer on direct-conversion molecular breast imaging using a standardized lexicon and to determine how often direct-conversion molecular breast imaging identifies all known invasive tumor foci in the breast, and whether this differs for invasive ductal versus lobular histologic profiles. Patients with prior invasive breast cancer and concurrent direct-conversion molecular breast imaging examinations were retrospectively reviewed. Blinded review of direct-conversion molecular breast imaging examinations was performed by one of two radiologists, according to a validated lexicon. Direct-conversion molecular breast imaging findings were matched with lesions described on the pathology report to exclude benign reasons for direct-conversion molecular breast imaging findings and to document direct-conversion molecular breast imaging-occult tumor foci. Associations between direct-conversion molecular breast imaging findings and tumor histologic profiles were examined using chi-square tests. In 286 patients, 390 invasive tumor foci were present in 294 breasts. A corresponding direct-conversion molecular breast imaging finding was present for 341 of 390 (87%) tumor foci described on the pathology report. Invasive ductal carcinoma (IDC) tumor foci were more likely to be a mass (40% IDC vs 15% invasive lobular carcinoma [ILC]; p < 0.001) and to have marked intensity than were ILC foci (63% IDC vs 32% ILC; p < 0.001). Direct-conversion molecular breast imaging correctly revealed all pathology-proven foci of invasive disease in 79.8% of cases and was more likely to do so for IDC than for ILC (86.1% vs 56.7%; p < 0.0001). Overall, direct-conversion molecular breast imaging showed all known invasive foci in 249 of 286 (87%) patients. Direct-conversion molecular breast imaging features of invasive cancer, including lesion type and intensity, differ by histologic subtype. Direct-conversion molecular breast imaging is less likely to show all foci of ILC compared with IDC.

Abstract LB-001: Development and evaluation of a fluorescent antibody-drug conjugate for molecular imaging and targeted therapy of pancreatic cancer

Abstract Developing new strategies to effectively diagnose and treat various types of cancer is paramount to increasing patient survival rates. Although chemotherapeutic small molecules are effective for some cancer types, they often have harmful side effects, resulting in significant damage to healthy tissue. Targeted therapy, where anti-cancer drugs are more precisely delivered to specific cells, has the potential to revolutionize chemotherapy, through increased localized effective doses with minimized systemic toxicity. Antibody-drug conjugates (ADCs) are one such class of targeted therapy biopharmaceuticals, employing the inherent specificity of antibodies as a targeting mechanism to yield a potent drug delivery system. In addition to being used as ADCs, antibody-conjugates are also commonly used as a highly effective tool for cancer typing and longitudinal treatment monitoring by immunohistochemistry staining or diagnostic imaging. However, antibody-conjugates used for tumor diagnosis and treatment are different molecules. Fluorescent dye labeling of therapeutic antibodies has been previously demonstrated for cancer imaging. However, therapeutic antibodies dual-labeled with both chemotherapeutic small molecules and fluorescent dyes has not been reported. Here, we demonstrate the development of a directly-labeled, fluorescent antibody-drug conjugate for simultaneous targeted drug delivery and in vivo molecular imaging of cancer. Our novel biopharmaceutical entity is a monoclonal antibody specific for a carcinoembryonic antigen (CEA) biomarker conjugated to an average of one molecule of paclitaxel and two molecules of a near-infrared fluorophore (DyLight 680-4xPEG). Preliminary data show that this fluorescent ADC selectively binds CEA positive cells and is cytotoxic using in vitro model systems. Ongoing studies using an in vivo mouse xenograft cancer model will demonstrate the utility of this fluorescent ADC as a new concurrent pancreatic cancer detection, monitoring and treatment technology. Citation Format: Steve Knutson, Erum Raja, Ryan Bomgarden, Marie Nlend, Aoshuang Chen, Ramaswamy Kalyanasundaram, Surbhi Desai. Development and evaluation of a fluorescent antibody-drug conjugate for molecular imaging and targeted therapy of pancreatic cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-001. doi:10.1158/1538-7445.AM2015-LB-001