Current Molecular Imaging (v.2, #2)

Glioblastoma is an aggressive form of brain tumor with a poor outcome. Recent advancements using moleculartechniques have identified subtypes of glioblastoma that have emerged from the traditional classification. The molecularsubtypes are associated with different prognoses and responses to treatment. Both features make molecular sub-typing importantin the clinical setting. Detection of each subtype, or key mutations within, currently occurs post-surgically usinghistological and biochemical based techniques. Non-invasive imaging, particularly magnetic resonance imaging (MRI), isan integral part of glioblastoma diagnosis and patient management. Whether non-invasive imaging can identify molecularsubtypes pre-surgically is likely to be true based on recent proof of concept approaches. Correlating molecular subtypesand imaging features will led to more detailed subtypes, a greater stratification of patients, and assignment of the besttreatment option. This review summaries the current molecular subtypes based on telomere maintenance mechanisms orgenomic approaches, key genetic markers in each tumor subtype, and whether these markers correlate with patient prognosis.An outline of methods to distinguish tumor subtypes is given including efforts toward detecting molecular changesby non-invasive imaging.

Evaluation of Tophaceous Gout by FDG-PET/CT and Bone Scan by Gottfried Wimmer, Simon W. Stoecklegger, Tatjana Stojakovic, Josef F. Hofer, Robert Pichler (117-119).
We report the case of a 76 year old male patient with a clinical history of gouty arthritis and multiple enormousgouty tophus for decades. Medical history as well presented prostate cancer, arterial hypertension and chronic atrial fibrillation.Hospitalisation became necessary in October 2011 due to duodenal ulcer. At this time no specific medication forgout was taken. Serum urine acid and CRP were in the normal range. Bone scan showed multifocal arthritis in small fingerjoints of both hands, activation was present only in the left PIP joint of digit IV. The diphosphonate tracer was notcaptured by the subcutaneous tophus of the right hand. Additional evaluation of inflammatory processes by FDG-PET/CTwas done in succession, both tophi presented augmented glucose metabolism with an SUV of about 2. After efficienttreatment with proton pump inhibitors and healing of ulcer disease verified by endoscopic control examination, medicationfor gout with allopurinol and diclofenac was reinitialised. We recommend to consider the use of nuclear medicine imagingin gouty arthritis and tophus additionally to radiological methods or via hybrid imaging to visualise inflammation injoints and further involved tissue.

Application of Radiolabeled Antibodies in Targeting Therapy of Breast Cancer by Zahra Heidari, Mojtaba Salouti, Reyhaneh Sariri (120-129).
Breast cancer continues to be the second-leading cause of cancer in world. Early detection, improved surgicaltechniques, and more effective therapy methods have improved quality of life and survival for patients, particularly thosewith less advanced diseases. Therefore, tremendous amounts of time and efforts are dedicated to search toward earlier detectionand more efficient treatment of breast cancer. Advances in molecular cancer biology achieved an increased understandingof the biologic factors that contribute to breast cancer pathogenesis and progression. This understanding has alreadyled to more effective treatment. Among different therapy modalities, nuclear medicine provides an important role tothe clinical management of breast cancer. In this review, the history of radioimmunotherapy of breast cancer as a targetedmolecular method is reviewed.

The Neurotachykinin NK1 Receptor ? A Novel Target for Diagnostics and Therapy by Susanne Nikolaus, Maria Angelica de Souza Silva, Hubertus Hautzel, Hans-Wilhelm Muller (130-147).
Despite the knowledge, which has been accumulated on the central and peripheral actions of the neurokinin(NK) substance P (SP) over the last 80 years, it is only beginning to receive the attention of nuclear medicine physiciansand scientists. Recently, two foci of interest have emerged: firstly, the performance of in vivo imaging studies of cerebralNK1 receptor binding with non-peptidergic NK1 receptor radioligands, and, secondly, radionuclide therapy with radiolabelledSP analogues targeting NK1 receptor binding sites. The present paper gives an overview on the utilization of nonpeptidergicand peptidergic NK1 receptor radioligands in diagnostics and therapy.

Recent revolutionary developments in luciferase engineering technologies now allow researchers to carry outquantitative imaging of molecular dynamics and cell signaling in living subjects, the technology of which includesprotein-fragment complementation assay (PCA) and intein-mediated protein splicing assay (PSA). These technologies arefunctionally optimized with specific marine and beetle luciferases exerting designed properties and functionalities. Thisreview overviews how to fabricate such bioluminescent tools and technologies of reconstituting split-luciferases, providing anexcellent platform for today?s molecular imaging.

Local Recurrence vs Radiotherapy-Induced Edema in Advanced Laryngeal Carcinoma: Is FDG PET/CT Up to the Challenge? by Sagi Tshori, Martine Klein, Jeffrey Weinberger, Roland Chisin, Nanette Freedman (158-163).
Head-and-neck squamous cell carcinoma (HNSCC) is a high-risk disease. Historically, treatment often involvedmutilating surgery, with devastating implications for quality of life, particularly in patients with advanced-stage laryngealsquamous cell carcinoma (ALSCC). Treatment for ALSCC always included total laryngectomy. Nowadays,treatment with more effective chemoradiotherapy regimes in newly diagnosed patients may often avoid total laryngectomy;however recurrence rates are relatively high. Techniques for early identification of recurrence or residual diseasehave therefore become crucial. Clinical diagnosis by laryngoscopy is problematic; radiotherapy induced laryngeal edema,which may persist for years, can mask local disease, resulting in detection at a late stage when total laryngectomy isunavoidable.</p><p>F18-2-fluoro-2-deoxy-D-glucose (FDG) PET/CT has emerged as an excellent imaging tool in the diagnosis and follow-upof HNSCC patients. In this review, we discuss experience with FDG PET/CT for follow-up of ALSCC after radiotherapy.While there is a high negative predictive value for FDG PET/CT in this situation, as in other HNSCC cases, a high rate offalse positive findings in the larynx is described. Increased FDG uptake may be due to ongoing inflammation in the regionof persistent edema, and may result in repeated laryngeal biopsies, with potentially deleterious long-term consequences.</p><p>FDG PET/CT is an efficient imaging modality for the diagnosis and follow-up of HNSCC patients, but has limitations inthe follow-up of ALSCC post-radiotherapy—benefits and risks must be weighed with caution.

In Vivo Monitoring of Cell Based Therapy in the Liver by Ashwini Ketkar-Atre, Uwe Himmelreich (164-176).
The high mortality in the final stage of certain liver diseases and the lack of whole organ donors for liver transplantationrequire alternative therapeutic approaches. Cell based therapy has been one of the promising approaches fortreating liver diseases. Hereby, the utilization of hepatocytes or stem cells differentiated towards functional hepatocyteshas been studied intensively. In order to validate the success of those approaches, it is necessary to monitor the location,homing and functionality of engrafted cells longitudinally and non-invasively. This has been possible with the help of imagingmodalities like magnetic resonance imaging, positron emission tomography and optical imaging methods. All thosemethods require contrast agents, tracers or imaging reporters that track not only the location of transplanted cells but alsovisualize their functional status in vivo.</p><p>In this review, we provide an overview of possible contrast agents and tracers for liver imaging, an outline of imaging approachesfor tracking transplanted cells in the liver and discuss imaging strategies to assess liver function non-invasively.Hereby, a strong focus will be on the assessment of imaging markers for the different modalities in experimental modelsfor normal and diseased liver. We conclude the review with the possible advantages of such markers for diagnosis andmonitoring of disease progression and therapy assessment over currently available imaging modalities.

Biological Applications of ZnO Nanoparticles by Hua-Juan Zhang, Huan-Ming Xiong (177-192).
Over the past few years, ZnO nanoparticles have attracted great attention due to their biocompatibility and lowcost. A number of investigations demonstrated their potential applications in biotechnology and biomedicine. This reviewpresents the current biological applications of ZnO nanoparticles, including biological imaging, drug releasing andbiosensing, as well as their advantages and limitations in these areas. In addition, the toxicity of ZnO nanoparticles isdiscussed in comparison with other conventional nanoparticles.