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New and improved imaging methods have recently become available, assuming a crucial role not only in clinical practice—in which they are indispensable in the diagnostic evaluation and therapeutic management of patients—but also in preclinical research. In this field, miniaturized versions of clinical diagnostic modalities have greatly improved our ability to longitudinally study various animal models of human disease. These modalities include, but are not limited to X-ray, micro-ultrasonography, micro–magnetic resonance imaging, micro–computed tomography (CT), and radionuclide imaging such as micro–positron emission tomography and micro–single photon emission CT. This chapter describes the most common applications of the different instruments for diagnostic imaging and their relative advantages and disadvantages.

Peptides (from the Greek πeπτίδια, “small digestibles”) are short polymers formed from the linking, in a defined order, of two or more α-amino acids. The link between one amino acid residue and the next is called an amide bond or a peptide bond. A protein, sometimes referred to as a polypeptide, is a long chain of amino acids joined together in this way. Some proteins contain more than one polypeptide chain. Different interpretations are reported on the number of amino acids that distinguish a peptide from a protein, with the definition of peptide being generally accepted already for molecules constituted by only two amino acids linked with an amide bond. Using “peptides” as the keyword in PubMed, we found 1,784,203 and 1,856,490 articles, respectively, in a search performed on 16 June 2010 and repeated on 20 December 2010. Searching separately for peptides and diagnostic imaging, peptides and nuclear medicine, peptides and therapy, peptides and radionuclide therapy, while a relevant percentage of publications on diagnostic imaging is connected with nuclear medicine, relatively few are associated with radionuclide applications with respect to the whole number of therapeutic procedures, involving more widely non-radiolabelled peptides. This is a further stimulus to the discussion, defining the possible value of diagnostic imaging as an instrument to predict therapeutic response to peptides both radiolabelled or not.

The aim of the study was to evaluate a novel polar map of myocardial viability obtained by gated SPECT imaging to predict functional recovery after revascularization in patients with ischaemic left ventricular (LV) dysfunction. The study group comprised 17 patients (15 men, mean age 58 +/- 9 years) with ischaemic LV dysfunction (ejection fraction

Positron Emission Tomography (PET) is a diagnostic imaging procedure used regularly to acquire essential clinical information. The PET – CT hybrid, which consists of two scanning machines: PET scanner and an x-ray Computed Tomography (CT). At present these represent the technological hierarchy of Nuclear Medicine, occupying an important position in diagnostics. In fact, PET – CT has the capability to evaluate diseases through a simultaneous functional and morphostructural analysis. This allows for an earlier diagnosis of the disease state which is crucial for obtaining the required information to provide a more reliable prognosis and therapy. Presently, the most frequently used PET radiotracer [18F]fluorodeoxyglucose (FDG) has a major role in oncology. Useful information is being regularly obtained by using both FDG and a selection of radiotracer compounds to evaluate some of the most important biological processes. Thus, creating an opening for ‘Molecular Imaging’ and providing a platform for a potential revolution in the clinical diagnostic field. In this review, we hope to present the most interesting technicalogical and methodological advances in clinical diagnostics for oncology, neurology, and cardiology. A particular attention is dedicated to the applications of PET in neuropsychiatric diseases and its connections with receptor imaging.

The aim of this study was to investigate the predictive potential of pre-operative regional cerebral blood flow (rCBF) in the pre-supplementary motor area (pre-SMA) and clinical factors in Parkinson’s disease (PD) patients treated with subthalamic nucleus (STN) stimulation. Methods Ten patients underwent rCBF SPECT and motor Unified Parkinson’s Disease Rating Scale (UPDRS) preand post-operatively during stimulation at 5 and 42 months. Statistical parametric mapping (SPM) was used to extract rCBF values in the pre-SMA because it is related with motor improvement. Post-operative outcomes included motor response to stimulation and percent improvement in UPDRS. Pre-operative predictors were explored by correlation test, linear regression and multivariate analyses. Results Higher pre-operative rCBF in the pre-SMA and younger age were associated with favourable outcomes at 5 and 42 months. Pre-operative rCBF results were significantly associated with baseline clinical factors. Conclusion This study shows that PD patients with younger age have higher rCBF values in the pre-SMA and better outcome, thus giving the rationale to the hypothesis that STN stimulation could be considered early in the course of disease.

Huntington disease (HD) mutation increases gain-of-toxic functions contributing to glutamate-mediated excitotoxicity. Riluzole interferes with glutamatergic neurotransmission, thereby reducing excitotoxicity, enhancing neurite formation in damaged motoneurons and increasing serum concentrations of BDNF, a brain cortex neurotrophin protecting striatal neurons from degeneration.We investigated metabolic and volumetric differences in distinct brain areas between 11 riluzole-treated and 12 placebo-treated patients by MRI and (18)F-fluoro-2-deoxy-D-glucose (FDG) PET scanning, according to fully automated protocols. We also investigated the influence of riluzole on peripheral growth factor blood levels.Placebo-treated patients showed significantly greater proportional volume loss of grey matter and decrease in metabolic FDG uptake than patients treated with riluzole in all cortical areas (p0.05). The decreased rate of metabolic FDG uptake correlated with worsening clinical scores in placebo-treated patients, compared to those who were treated with riluzole. The progressive decrease in metabolic FDG uptake observed in the frontal, parietal and occipital cortex correlated linearly with the severity of motor scores calculated by Unified Huntington Disease Rating Scale (UHDRS-I) in placebo-treated patients. Similarly, the rate of metabolic changes in the frontal and temporal areas of the brain cortex correlated linearly with worsening behavioural scores calculated by UHDRS-III in the placebo-treated patients. Finally, BDNF and transforming growth factor beta-1 serum levels were significantly higher in patients treated with riluzole.The linear correlation between decreased metabolic FDG uptake and worsening clinical scores in the placebo-treated patients suggests that FDG-PET may be a valuable procedure to assess brain markers of HD.

Due to different sizes of humans and rodents, the performance of clinical imaging devices is not enough for a scientifically reliable evaluation in mice and rats; therefore dedicated small-animal systems with a much higher sensitivity and spatial resolution, compared to the ones used in humans, are required. Smallanimal imaging represents a cutting-edge research method able to approach an enormous variety of pathologies in which animal models of disease may be used to elucidate the mechanisms underlying the human condition and/or to allow a translational pharmacological (or other) evaluation of therapeutic tools. Molecular imaging, avoiding animal sacrifice, permits repetitive (i.e. longitudinal) studies on the same animal which becomes its own control. In this way also the over time evaluation of disease progression or of the treatment response is enabled. Many different rodent models have been applied to study almost all kind of human pathologies or to experiment a wide series of drugs and/or other therapeutic instruments. In particular, relevant information has been achieved in oncology by in vivo neoplastic phenotypes, obtained through procedures such as subcutaneous tumor grafts, surgical transplantation of solid tumor, orthotopic injection of tumor cells into specific organs/sites of interest, genetic modification of animals to promote tumor-genesis; in this way traditional or innovative treatments, also including gene therapy, of animals with a cancer induced by a known carcinogen may be experimented. Each model has its own disadvantage but, comparing different studies, it is possible to achieve a panoramic and therefore substantially reliable view on the specific subject. Small-animal molecular imaging has become an invaluable component of modern biomedical research that will gain probably an increasingly important role in the next few years.

Introduction The present review was conceived for describing the differences in biodistribution and diagnostic performance of two types of 18 F-radiolabeled choline for positron emission tomography (PET) imaging in prostate cancer (PCa), such as fluoromethylcholine (FCH) and fluoroethylcholine (FEC). Materials and methods A collection of published data about two radiopharmaceutical agents was made by using PubMed, Web of Knowledge databases and Trip Database, and then a critical revision was discussed. Results FCH was injected in 338 and 1164 patients, while FEC was injected in 20 and 139 patients, respectively for basal staging and re-staging. The diagnostic performances of FCH and FEC for the detection of lymph node metastasis before the surgical approach are typically around 50% or less and between 0% and 39%, respectively. Conversely, both the tracers appear useful for the detection of recurrent PCa in case of increase in absolute PSA value or in case of high levels of PSA velocity and PSA doubling time (sensitivity ranged between 42.9% and 96% for FCH and between 62% and 85.7% for FEC). Conclusions In according with the available information, FCH appears to be a more appropriate radiocompound as compared to FEC, although more comparative data are mandatory. A well designed and prospective trial for the evaluation of biokinetic data and diagnostic performance of both radiopharmaceutical agents seems essential. Advances in knowledge and implication for patient care FCH seems to be an appropriate radiopharmaceutical agent as compared to FEC. Anyway both the radiocompounds are useful in the evaluation of recurrent disease in case of a serial increase in PSA value and their performance improves when a correct preparation and acquisition protocol is employed.

Nodular thyroid disease is a very common finding in clinical practice, discovered by ultrasound (US) in about 50 % of the general population, with higher prevalence in women and in the elderly [1–4]. Whereas therapeutic flowchart is quite established and shared for malignant lesions, multiple options are now available for patients presenting with benign thyroid nodules, ranging from simple clinical and US follow-up to thyroid surgery. The majority of thyroid nodules, benign by fine-needle aspiration, are asymptomatic, stable, or slow-growing over time and require no treatment. Nevertheless, large thyroid nodules may become responsible for pressure symptoms, resulting in neck discomfort, cosmetic complaints, and decreased quality of life. Partial/total thyroid surgery has so far constituted the only therapeutic approach for these. Although surgery is widely available, highly effective, and safe in skilled centers, complications (both temporary and permanent) still occur in 2–10 % of cases [5, 6]. Hypothyroidism is an unavoidable effect after total thyroidectomy, requiring lifelong l-thyroxine replacement therapy. Besides, surgery is expensive and may be not recommended for high-risk patients or refused by others. Radioiodine (131I) therapy has been proven to be effective to treat toxic multinodular goiters and autonomously functioning thyroid nodules (AFTN) [7], although they are usually more radioresistant than toxic diffuse goiters [8]. Radioiodine therapy normalizes thyroid function and significantly reduces thyroid volume. However, hypothyroidism often occurs, in up to 60 % of patients, several years after treatment [9]. Otherwise, radioiodine therapy shows only incomplete, weak effects in nonfunctioning cold thyroid nodules. Pretreatment with recombinant human TSH may improve goiter volume reduction by causing a more homogeneous distribution of radioiodine within the gland, especially increasing the uptake of 131I in scintigraphically relatively cold areas [10]. TSH-suppression therapy withl-thyroxine was widely used to achieve nodule shrinkage and to prevent nodule growth and formation, producing, however, controversial results and exposing patients to heart and bone side effects. Therefore, current guidelines do not recommend its routine use in clinical practice, suggesting its usefulness in some cases only [3, 4]. Over the last two decades, nonsurgical, minimally invasive, US-guided techniques have been proposed for the treatment of thyroid nodules [11–16]. Percutaneous ethanol injection (PEI) is recommended for the treatment of relapsing cysts and dominantly cystic thyroid nodules [17]. Because of the limitations of PEI in the management of solid thyroid nodules, hyperthermic methods (laser ablation and radiofrequency ablation) have been introduced afterward for the treatment of solid, benign thyroid lesions [18], achieving marked nodule size reduction and clinical improvement in nodule-related symptoms, in several series from skilled centers, especially in Korea and Italy. Other nonsurgical therapies, such as high-intensity focused-ultrasound (HIFU), microwaves, cryotherapy, and electroporation, are presently under investigation.

Transient osteoporosis is an infrequent condition of uncertain etiology with pain, limited range of motion and radiographic evidence of osteoporosis affecting one or more joints. It is self-limited, reversible and can involve only the hip (transient osteoporosis of the hip, TOH) or, less frequently, one or more joints contemporaneously or at different times (regional migratory osteoporosis, RMO). We studied four men with transient osteoporosis, including two with TOH and two with RMO. All patients underwent a standard radiographic work-up of the affected joints, arteriovenous Doppler US, computed tomography, magnetic resonance imaging (MRI) and three-phase bone scanning. In all patients, symptoms were related to bone marrow edema demonstrated at MRI and to a transitory regional arterial hyperflow observed at the early scintigraphic analysis. On the basis of our observations, we hypothesize that regional arterial hyperflow may be the cause of the bone marrow edema and therefore of the transient osteoporosis.

The present review was conceived for describing the differences in biodistribution and diagnostic performance of two types of (18)F-radiolabeled choline for positron emission tomography (PET) imaging in prostate cancer (PCa), such as fluoromethylcholine (FCH) and fluoroethylcholine (FEC).A collection of published data about two radiopharmaceutical agents was made by using PubMed, Web of Knowledge databases and Trip Database, and then a critical revision was discussed.FCH was injected in 338 and 1164 patients, while FEC was injected in 20 and 139 patients, respectively for basal staging and re-staging. The diagnostic performances of FCH and FEC for the detection of lymph node metastasis before the surgical approach are typically around 50% or less and between 0% and 39%, respectively. Conversely, both the tracers appear useful for the detection of recurrent PCa in case of increase in absolute PSA value or in case of high levels of PSA velocity and PSA doubling time (sensitivity ranged between 42.9% and 96% for FCH and between 62% and 85.7% for FEC).In according with the available information, FCH appears to be a more appropriate radiocompound as compared to FEC, although more comparative data are mandatory. A well designed and prospective trial for the evaluation of biokinetic data and diagnostic performance of both radiopharmaceutical agents seems essential.FCH seems to be an appropriate radiopharmaceutical agent as compared to FEC. Anyway both the radiocompounds are useful in the evaluation of recurrent disease in case of a serial increase in PSA value and their performance improves when a correct preparation and acquisition protocol is employed.

The aim of modern intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) is to define the target areas including the smallest non-invaded margins, thus reducing the radiation dose to radiosensitive organs. To reach this goal, these methods require a more precise target delineation by imaging to better define the viable part of the tumor. Image-guided selection and demarcation of Gross Tumor Volume (GTV), Clinical Target Volume (CTV) and Organs at Risk (OAR) are the main steps to reach a satisfactory radiation treatment plan. Hybrid machines, such as PET-CT, SPECT-CT and, more recently, PET-MRI, may significantly increase diagnostic accuracy improving either sensitivity and specificity achievable alone by the single constituents of the hybrid tools. While the implementation contribution of PET-CT in radiotherapy, with respect to CT stand alone, has been extensively and successfully investigated, few papers have been at present written on the possible role of SPECT-CT for the same purpose. With an identical contribution to CT, SPECT may give similar information with respect to PET, when suitable radiopharmaceuticals are available. In particular, SPECT may provide additional information to CT, better defining the viable tumor mass; as a consequence, a more effective delineation of the GTV, saving the maximum normal tissue as possible, may be allowed. In this paper, we review some of the most important applications of SPECT-CT in oncology, as a premise to its possible utilization in tumor target definition in radiotherapy. In particular, we discuss sentinel lymph node (SLN) detection, tumor imaging with cationic lipophilic radiotracers, as (99m)Tc-methoxyisobutylisonitrile (MIBI) and (99m)Tc-tetrofosmin (TF) in breast cancer, thymoma, and lung cancer, (99m)Tcmethylene diphosphonate (MDP) for bone scan, (131)Iodine and (123)Iodine in differentiated thyroid cancer (DTC), as useful methods to optimize GTV and CTV definition. A reflection on the possible role in radiotherapy of other radiotracers labeled with gamma emitters, such as In-111 pentreotide has also been included.

1401 Objectives NGR peptides could specifically target to aminopeptidase N (APN) which was highly expressed in tumor and angiogenic endothelial cells. Fcy, a yeast cytosine deaminase, can convert 5-fluorocytosine (5-FC) prodrug into cytotoxic 5-fluorouracil (5-FU). This study developed a targeted enzyme-mediated prodrug activation therapy, NGR-Fcy/5-FC, and characterized in sarcoma animal models. Methods NGR-Fcy and Fcy recombinant protein were both constructed and purified from E.coli with high yield (15 mg/L). The enzyme activity, in vitro binding affinity and cytotoxicity were assayed. Both NGR-Fcy and Fcy were labeled with I-131 to give their radioactive surrogates with high radiochemical purities. The biodistribution study of HT1080 tumor bearing mice after intravenous injection of 131I-NGR-Fcy and 131I-Fcy was conducted. Results The 5-FC/5-FU-converting activity of NGR-Fcy (Km=0.56±0.09 mM and Vmax=101.1±5.2 μM/m/μg) was similar to that of Fcy (Km=0.64±0.12 mM and Vmax= 107.8±7.2 μM/m/μg). NGR-Fcy could specifically bind to high APN-expressing tumor cells (HT1080) and endothelial cells (BAEC), but not to APN-negative cells (HT29). After NGR-Fcy/5-FC treatment, the viability of HT1080 and BAEC was significantly reduced (IC50= 14.8±0.4 and 33.4±0.4 μM, respectively), while that of HT29 was not (IC50= 39430.4±347.2 μM). The tumor uptake of 131I-NGR-Fcy was higher than that of 131I-Fcy in HT1080 tumor bearing mice. Conclusions This study developed a prodrug activation therapy system, NGR-Fcy/5-FC, which can specifically bound to high APN-expressing tumor and endothelial cells and exhibit remarkable cytotoxicity by converting 5-FC to 5-FU. Research Support This work was supported by Grants from the National Science Council of Taiwan (NSC 102-2627-M-010-002 and NSC 102-2627-M-010-001).