Peptides and Somatostatin Analogues

Neuroendocrine tumours (NET) are rare tumours that occur most commonly in the GI tract. Various labelled somatostatin analogues are used to image NET expressing somatostatin receptors (SSTR). In traditional nuclear medicine, most peptides used in imaging NET have been labelled with indium-111, the commonest being indium-111octreotide (111In-octreotide). Unfortunately, the unfavourable physical qualities of In-111 make it unsuitable for detecting small tumour deposits. The recent introduction of gallium68-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (gallium-68-DOTA) compounds for positron emission tomography (PET) imaging has significantly improved the quality of imaging NET through improved resolution of PET and higher affinity of the new generation of peptides to SSTR. In the present paper, we discuss the clinical and research applications of PET radio-tracers for evaluating NET, in particular gallium-68-DOTA compounds. The recent introduction of PET imaging with gallium-68 has major bearings in current and future clinical practice. Its labelling with DOTA compounds has cleared the way for somatostatin receptor imaging with a viable PET agent, with all its inherent imaging advantages compared to single photon imaging. The pre-clinical and clinical applications of this technique has been successful in a variety of tumours, particularly NET and its labelling with other ligands and molecules will improve the management of other tumours and the assessment of infection. Labelled peptides, particularly labelled somatostatin analogues, have been increasingly used in the diagnosis and therapy of tumours expressing somatostatin receptors (SSTR) on their cell surface, particularly neuroendocrine tumours (NET). Generally, NET are rare tumours and occur most commonly in the GI tract. The most common are carcinoid tumours and the gastroenteropancreatic tumours (GEP) such as gastrinomas and insulinomas. Other tumours expressing SSTR include somatostatinomas, medullary thyroid tumours, pituitary tumours, paragangliomas and phaeochromocytomas. To date, most peptides used in imaging NET have been labelled with indium-111, the commonest being indium-111octreotide (111In-octreotide). The physical qualities of In111, even allowing for the use of single photon emission computed tomography (SPECT), make it unsuitable for detecting small tumours. Likewise, the currently available peptides may have a reduced rate of accumulation in tumours due to their variable affinity to one or more of the five SSTR manifested on cell surfaces. The recent introduction of gallium-68-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (gallium-68DOTA) compounds for PET imaging has significantly improved the quality of imaging NET through improved resolution of PET and higher affinity of the new generation of peptides to SSTR. The clinical use of this new technique and its implication on research is discussed in this review. Peptides and Somatostatin Analogues Peptides comprise a variable number of amino acids and have fast clearance, rapid tissue penetration, and low antigenicity, and can therefore be produced easily and inexpensively. There has been a significant increase in the development of labelled peptides for diagnostic applications in the last decade especially due to simplified methods of purification. An inherent added advantage to this diagnostic approach is its therapeutic implication since if the diagnostic 4087 Correspondence to: Domenico Rubello, MD, Head and Professor, Nuclear Medicine, PET Unit, S. Maria della Misericordia Hospital, Istituto Oncologico Veneto (IOV)-IRCCS, Viale Tre Martiri 140, 45100, Rovigo, Italy. Tel: +39 0 425 394427, Fax: +39 0 425 394434, e-mail: [email protected]