The role of heterodimerization between VEGFR-1 and VEGFR-2 in the regulation of endothelial cell homeostasis

VEGF-A activity is tightly regulated by ligand and receptor availability. Here we investigate the physiological function of heterodimers between VEGF receptor-1 (VEGFR-1; Flt-1) and VEGFR-2 (KDR; Flk-1) (VEGFR(1-2)) in endothelial cells with a synthetic ligand that binds specifically to VEGFR(1-2). The dimeric ligand comprises one VEGFR-2-specific monomer (VEGF-E) and a VEGFR-1-specific monomer (PlGF-1). Here we show that VEGFR(1-2) activation mediates VEGFR phosphorylation, endothelial cell migration, sustained in vitro tube formation and vasorelaxation via the nitric oxide pathway. VEGFR(1-2) activation does not mediate proliferation or elicit endothelial tissue factor production, confirming that these functions are controlled by VEGFR-2 homodimers. We further demonstrate that activation of VEGFR(1-2) inhibits VEGF-A-induced prostacyclin release, phosphorylation of ERK1/2 MAP kinase and mobilization of intracellular calcium from primary endothelial cells. These findings indicate that VEGFR-1 subunits modulate VEGF activity predominantly by forming heterodimer receptors with VEGFR-2 subunits and such heterodimers regulate endothelial cell homeostasis

Nuclear medicine procedures in neuroblastoma

In NB diagnostic setting, nuclear medicine procedures have demonstrated major accuracy for both staging and treatment response assessments, including the evaluation of bone and bone marrow involvement. 123I-MIBG scintigraphy has been extensively used in research and clinical practice for over 35 years, representing the most important functional imaging modality in NB assessment. Furthermore, therapy with 131I-MIBG has been extensively employed in neuroblastoma since the late 1980s, with a systematic review analyzing 1121 patients treated with 131I-MIBG. 131I-MIBG was used as single agent (monotherapy) in patients with a poor prognosis, in particular those with recurrent/refractory disease, as a palliative treatment. So far, 131I-MIBG therapy is included in multicentric trials on high-risk neuroblastoma patients. However, in recent years, different types of “new” PET tracers have been introduced in the diagnostic workup of NB showing very promising results [21, 22]. In this new diagnostic scenario, it seems important to identify strengths and limitation of each different functional diagnostic modality. The aim of this chapter is to analyze, in terms of availability and accuracy, the principal nuclear medicine procedures used in NB. In addition, the prevalent or complementary role of each functional imaging method is highlighted

EANM 2012 guidelines for radionuclide imaging of phaeochromocytoma and paraganglioma

Item does not contain fulltextPURPOSE: Radionuclide imaging of phaeochromocytomas (PCCs) and paragangliomas (PGLs) involves various functional imaging techniques and approaches for accurate diagnosis, staging and tumour characterization. The purpose of the present guidelines is to assist nuclear medicine practitioners in performing, interpreting and reporting the results of the currently available SPECT and PET imaging approaches. These guidelines are intended to present information specifically adapted to European practice. METHODS: Guidelines from related fields, issued by the European Association of Nuclear Medicine and the Society of Nuclear Medicine, were taken into consideration and are partially integrated within this text. The same was applied to the relevant literature, and the final result was discussed with leading experts involved in the management of patients with PCC/PGL. The information provided should be viewed in the context of local conditions, laws and regulations. CONCLUSION: Although several radionuclide imaging modalities are considered herein, considerable focus is given to PET imaging which offers high sensitivity targeted molecular imaging approaches