99mTc-EDDA/HYNIC-TOC is a New Opportunity in Neuroendocrine Tumors of the Lung (and in other Malignant and Benign Pulmonary Diseases).

Neuroendocrine tumors (NETs) consist of a relatively rare spectrum of malignancies that can arise from neuroendocrine cells; lung NETs (L-NETs) represent about 25% of primary lung neoplasm and 10% of all carcinoid tumors. Diagnostic algorithm usually takes into consideration chest Xray, contrast-enhanced CT and MRI. Nuclear medicine plays a crucial role in the detection and correct assessment of neoplastic functional status as it provides in vivo metabolic data related to the overexpression of Somatostatin Receptors (SSTRs) and also predicting response to peptide receptor radionuclide therapy (PRRT). 111In-Pentreotide (Octreoscan®) is commercially available for imaging of neuroendocrine tumors, their metastases and the management of patients with NETs. More recently, 99mTc-EDDA/HYNIC-TOC(Tektrotyd®) was introduced into the market and its use has been approved for imaging of patients with L-NETs and other SSTR-positive tumors. 99mTc-EDDA/HYNIC-TOC could also represent a good alternative to 68Ga-DOTA-peptides (DOTA-TOC, DOTA-NOC, DOTATATE) in hospitals or centers where PET/CT or 68Ge/68Ga generators are not available. When compared to 111In-Pentetreotide, Tektrotyd® showed slightly higher sensitivity, in the presence of higher imaging quality and lower radiation exposure for patients. Interesting perspectives depending on the kinetic analysis allowed by Tektrotyd® may be obtained in differential diagnosis of non-small cells lung cancer (NSCLC) versus small cells lung cancer (SCLC) and NETs. An interesting perspective could be also associated with a surgery radio-guided by Tektrotyd® in operable lung tumors, including either NETs and NSCLC.

Nuclear Medicine in Patients with NET: Radiolabeled Somatostatin Analogues and their Brothers.

Although Somastostatin (SS) scintigraphy (SRS) has been introduced many years ago, it remains the most diffuse radionuclide diagnostic tool in patients with neuroendocrine tumours (NETs). Being SS receptors (SSTR) expressed in the majority of NETs, radiolabeled SS analogues (SS-A) provide high diagnostic accuracy, mainly in patients with gastro-entero-pancreatic (GEP) tumors. SSTR are the best target for radiotracers used either for diagnostic and therapeutic purposes in NETs due to their presence on the surface of neoplastic cells of clinical interest. 111In- DTPA-octreotide (111In-Pentetreotide, Octreoscan®), may detect either primitive or secondary lesions in the presence of a satisfactory lesion/background ratio. The unsatisfactory diagnostic performance of 18F-Fluorodeoxyglucose (18F-FDG), in NETs stimulated the synthesis of more specific positron-emitting tracers and SS-A labeled with 68Gallium (DOTA-peptides) represent actually the best radionuclide procedure for NET imaging. Alternative radiotracers, labeled either with gamma or positron emitters and showing different uptake mechanisms, as 18F-DOPA (Fluorine- 18-L-dihydroxyphenylalanine), have also been proposed and clinically utilized. Octreoscan®, despite its limitations, continue to represent the most frequently used method in evaluating the response to treatment and in follow-up of patients with NET, although the better diagnostic accuracy of DOTA-peptides.

Small-Animal Molecular Imaging for Preclinical Cancer Research: .μPET and μ.SPECT.

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.