Mack Forster Award Lecture Receptor nuclear medicine: vasointestinal peptide and somatostatin receptor scintigraphy for diagnosis and treatment of tumour patients

Abstract

Abstract. The multiple aspects of radioligand-receptor interactions do not only show a major impact of certain cell surface-bound receptors in the pathophysiology of human disease: the concept of radioligand-receptor interactions has also been extended to the clinic. In particular, naturally occurring peptides, when radiola-

Elucidation of Vasoactive Intestinal Peptide Pharmacophore for VPAC1Receptors in Human, Rat, and Guinea Pig

“…Recent reports propose a role of VIP in a number of clinically important areas, including asthma (Bolin et al, 1995); treatment of impotence (Sandhu et al, 1999); pain transmission (Dickinson and Fleetwood-Walker, 1999); pathogenesis of vascular headaches (Edvinsson, 2000); having a neuroprotective effect that could be used to treat Alzheimer's disease or Parkinson's disease (Offen et al, 2000); and having potent anti-inflammatory effects that could be useful in the treatment of septic shock, Crohn's disease, and rheumatoid arthritis (Gomariz et al, 2001;Said, 1996). In addition VIP receptors are highly expressed in a number of cancers, including those of the breast and gastrointestinal tract, and it has been shown these can be used to localize these tumors by imaging methods and, therefore, their presence may be important in various antitumor treatments (Virgolini, 1997).…”

Elucidation of the Vasoactive Intestinal Peptide Pharmacophore for VPAC2 Receptors in Human and Rat and Comparison to the Pharmacophore for VPAC1 Receptors

“…Important possible pathophysiological effects include its growth effects on cancer cells (Moody, 1996;Jiang et al, 1997;Zia et al, 2000); a potential treatment role for VIP has been proposed in asthma (Groneberg et al, 2001), impotence (Sandhu et al, 1999), various central nervous system disorders through a neuroprotective effect , and various inflammatory disorders, such as rheumatoid arthritis, because of its potent anti-inflammatory effects (Gomariz et al, 2001;Delgado et al, 2002). Furthermore, use of VIP in localizing various tumors such as breast and gastrointestinal cancers by imaging methods has been proposed because these tumors have a high density of VIP receptors (Virgolini, 1997).…”

Development of Simplified Vasoactive Intestinal Peptide Analogs with Receptor Selectivity and Stability for Human Vasoactive Intestinal Peptide/Pituitary Adenylate Cyclase-Activating Polypeptide Receptors

“…However, [Ala 2,8,9,16,19,24,25 ]VIP (analog 8) had high affinity and potency for both VPAC subtypes and was much more metabolically stable than VIP in cells containing each VPAC subtype. These simplified, metabolically stable analogs should be useful for investigating the role of VPAC 1 in biological and pathological processes, for enhanced imaging of tumors overexpressing VIP receptors using VIP receptor scintigraphy (Virgolini, 1997;Thakur et al, 2000Thakur et al, , 2004Rao et al, 2001;Bhargava et al, 2002) as well as for possible VIP receptordirected antitumor treatment for tumors overexpressing VPACs (Gotthardt et al, 2004;Moody et al, 2004;Ou et al, 2005).…”