Current Molecular Imaging (Discontinued) - Volume 2, Issue 1, 2013

Fluorescence imaging is nowadays a powerful tool for laboratory animal studies in oncology. This emerging technology is in full development and is becoming a complementary tool in clinics for specific cancer diagnosis. For now, it allows detection with a high spatio-temporal resolution of specific signals like tumor markers in small animals. Different ways of in vivo imaging exist: epifluorescence macroscopy, intravital imaging to visualize molecular processes combined or not with multiphoton excitation and fluorescence tomography to spatially detect deeper cellular phenomena. These techniques are impaired by the tissue optical properties: auto-fluorescence, photon scattering in tissues and by limited depth penetration of the excitation beam in tissues. To overcome these limits, scientists are developing spectral imaging, far-red imaging technologies and associated dyes to observe tumor cells biology over longer periods, on larger volumes and on a higher number of organs, thus improving the knowledge in tumor pathophysiology. A challenge in oncology is to improve early detection and prevention using novel targeted cancer diagnostics. Detection requests specific recognition. Tumor markers have to be ideally present on the surface of cancer cells. Their targeting with ligands coupled to imaging agents make them visible/detectable. In this review, after a short introduction on in vivo fluorescence imaging theories and a description of the different existing modalities, we will focus on the recent outcome of basic studies in the design of new probes and devices used to detect tumor cells.

Among all the preclinical imaging modalities available for scientifist to explore animal models, especially rodents, bioluminescence imaging (BLI), fluorescence and photoacoustic imaging strategies are the only ones that are not derived from medical imaging. Based on a chemical reaction involving an enzyme and its substrate to convert chemical energy into light emission, BLI is relatively recent (˜ 15 years). However, it is routinely used in many laboratories with regard to other modalities (MRI, PET, SPECT, CT). Thanks to its excellent sensitivity, the ability to perform high throughput exams, low cost and relative ease of implementation, bioluminescent imaging is widely used either for basic research or the development and screening of new therapies. After a brief introduction, we will describe the principle of bioluminescence, then discuss the main constraints for quantification, give some examples of routinely performed applications in oncology and finally provide some insights on new biological or technological approaches.

Perfusion computed tomography (CT) is an imaging technique that enables radiologists to evaluate the tumour vasculature, quantifying tumour perfusion, blood volume, and microcirculatory changes, which can provide both prognostic and predictive information to the clinician. Its increasing acceptance within oncology in recent years has been related to a combination of factors: an increasing use of anti-vascular therapy (anti-angiogenic agents and vascular disrupting agents) both as stand-alone first line agents or in combination with standard chemotherapy and/or radiotherapy, and technological improvements in CT, including faster tube rotation speeds, higher temporal sampling rates, the development of dynamic 3D acquisitions and development of commercial software programmes embedded within the clinical workflow. This review summarises current Perfusion CT techniques and their clinical application in oncological practice.

Understanding the hallmarks of cancer is valuable in advancing drug development to fight the disease. With the advent of molecular imaging, non-invasive in vivo visualization of physiology and functional pathways allow for multiple levels of disease and therapy assessment beyond tumor size measurements offered by conventional anatomic scans. Radiolabeling targeted molecules can provide insight into tumor interactions within the body and may help guide therapeutic constructs. Traditionally, radiolabeled probes have been useful for staging and diagnosis but they can also be created to monitor and identify drug targets and pharmaceutical biodistribution among other novel approaches. Radiotracers can be imaged either through single photon emission computed tomography (SPECT) or positron emission tomography (PET), with advantages and limitations to both. Adding CT to either modality is an added benefit for anatomic localization and attenuation correction. In this review, we will briefly discuss several molecular imaging agents, which target metabolism (18F-FDG, 18F-FACBC, 11C acetate), proliferation (18F-FLT, 18F-5FU, 18F-FdCyd), and cancer specific drug receptors (111In-morab009, 111In-trastuzumab, 89Zr-panutumumab). Molecular imaging is a powerful tool that one day, may be employed to personalize treatment and dosing strategies and predict anticancer therapy outcomes.

Magnetic resonance (MR) is often the modality of choice to image cancer patients. In standard-of-care clinical practice magnetic resonance imaging (MRI) is commonly used to obtain anatomical information based on physical properties of tissue water, but MR techniques are very versatile and can also be applied for functional and metabolic assessment. Metabolic aberrations are common in cancers either as a direct response to altered signal transduction, or as a consequence of increased cell proliferation, alterations in blood and substrate supply, tumor necrosis and hypoxia. Throughout the past years, magnetic resonance spectroscopy (MRS) has been utilized for the non-invasive radiological assessment of the chemical content of a distinct lesion within the body. Next to positron emission tomography (PET), MRS is defined as a metabolic imaging technique. Clinically, proton (1H-) MRS plays a dominant role, because of its high sensitivity, high abundance of the 1H nucleus in tissue metabolites and readily available clinical MR scanners, which are dedicated to observe 1H in water and fat for MRI. A typical feature in 1H-MR spectra of cancer patients is increased concentrations of total choline (tCho) which serve as a diagnostic and prognostic marker for staging and therapy response in brain, breast, prostate and ovarian cancers. Next to universally increased tCho (membrane phospholipid metabolism), abnormal levels of tissue specific metabolites have been reported for brain (decreased N-acetyl aspartate) and prostate (decreased citrate). Presently, high field MR magnets (3T and above) allow for faster acquisition and better resolution of in vivo1H-MRS in oncology. High-resolution magic angle spinning (HR-MAS) MRS has been successfully applied to small volume tumor biopsies, needle biopsies and fine-needle aspirates for fast and non-destructive ex vivo metabolic analysis. Pre-clinical development of 13C-hyperoplarized MRS in animal models (mostly with [1-13C]pyruvate as a tracer) will soon be translated into clinical 13C-MRS protocols for the assessment of glucose metabolism. This might facilitate the integration of PET and MR into a comprehensive multimodality platform for metabolic imaging in the foreseeable future.

Therapeutic strategies continue to evolve for treatment of women with cervical cancer. However there is dearth of validated biomarkers of therapeutic response and overall survival. In recent years development of molecular imaging techniques using Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) has allowed evaluation of imaging biomarkers of proliferation, angiogenesis, perfusion and hypoxia as prognostic imaging biomarkers. The present systematic review summarizes the current role of multifunctional PET and MRI as a response biomarker for cervical cancer.

Ultrasound imaging is still an attractive imaging modality thanks to its real-time character and low-cost. Recent technological developments in ultrasound imaging improved significantly the accuracy and confidence of clinical diagnoses. The clinical availability of ultrasound contrast agents over the past 20 years was one of the main recent developments in ultrasound imaging since contrast agents showed a major interest in various clinical situations, and mainly in cancer imaging for tumor perfusion studies. Tissue perfusion assessment allows the detection and characterization of tumor lesion but also the monitoring of anticancer therapy effectiveness. Recently, ultrasound molecular imaging has emerged as a promising tool for the visualization and the quantification of tumor angiogenesis. This new technique needs the development of targeted contrast agents that can bind to the molecular target. This review focuses on the contrast agents' properties and the specific methods currently used in ultrasound contrast agent imaging in oncology. Recent results and prospects in cancer molecular imaging are also discussed.

Cancer is one of the leading causes of death in the world. Diagnosing a cancer at its early stages of development can decrease the mortality rate significantly and reduce healthcare costs. Over the past two decades, photoacoustic imaging has seen steady growth and has demonstrated notable capabilities to detect cancerous cells and stage cancer. Furthermore, photoacoustic imaging combined with ultrasound imaging and augmented with molecular targeted contrast agents is capable of imaging cancer at the cellular and molecular level, thus opening diverse opportunities to improve diagnosis of tumors, detect circulating tumor cells and identify metastatic lymph nodes. In this paper we introduce the principles of photoacoustic imaging, and review recent developments in photoacoustic imagingas an emerging imaging modality for cancer diagnosis and staging.