Applied Radiation and Isotopes 65 (2007) 382–386 99m Tc(CO) 3 -VIP analogues: Preparation and evaluation as tumor imaging agent Kanchan Kothari a , Sudhanand Prasad b , Aruna Korde a , Archana Mukherjee a , Archana Mathur b , Manu Jaggi b , Meera Venkatesh a,Ã , Ambikalmajan M.R. Pillai c , Rama Mukherjee b , Natesan Ramamoorthy c a Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085, India b Dabur Research Foundation, 22, Site-IV, Sabibabad, Ghaziabad, Uttar Pradesh 201010, India c International Atomic Energy Agency, Wagramer Strasse 5, A-1400, Vienna, Austria Received 27 September 2006; accepted 2 November 2006 Abstract Vasoactive intestinal peptide (VIP) receptors are expressed abundantly on many types of tumors and, hence, radiolabeled VIP analogues are being explored for tumor imaging and therapy. Here, we report synthesis of three VIP analogues and their radiolabeling with 99m Tc via a novel tricarbonyl synthon. The radiolabeled product could be prepared in high yields (495%) and stability. In vitro studies showed significant uptake of 99m Tc(CO) 3 -VP05 in human colon carcinoma cells. Biodistribution studies in animal tumor model showed 0.4–1% ID/g tumor uptake. r 2006 Elsevier Ltd. All rights reserved. Keywords: VIP; Tumor imaging; 99m Tc(I) tricarbonyl complexes 1. Introduction Vasoactive intestinal peptide (VIP), a 28 amino acid neuropeptide, is known to bind to VIP receptors that are expressed in higher densities in various types of tumors (Virgolini et al., 1994; Pallela et al., 1999). VIP is considered as a universal peptide due to its ability to bind to majority of tumor types such as adenocarcinoma, colorectal cancers, tumors of GIT and liver, etc. Various VIP analogues have been synthesized and radiolabeled with suitable isotopes for tumor imaging and therapy (Rubi et al., 1996; Virgolini et al., 1995). It has been shown that labeling peptides with 99m Tc, an ideal diagnostic radionuclide, via Tc(V)-oxo core is generally unsuccessful due to disulfide bond reduction (Kolan et al., 1996). The 99m Tc(I) tricarbonyl complexes, that are kinetically inert, small in size and which can be prepared in high specific activities, have gained attention in the recent past (Schibli et al., 2000; Alberto et al., 1999, 1998). A convenient method for the synthesis of hydrophilic precursor fac-[ 99m Tc(OH 2 ) 3 (CO) 3 ] + in aqueous solution directly from 99m TcO 4  in saline and CO at normal pressure has been developed by Alberto et al. The precursor reacts with a variety of tridentate ligands under moderate conditions due to substitution ability of the three water moieties (Schibli et al., 2000; Alberto et al., 1998; Reisgys et al., 1997; Pietzsch et al., 2000). The N-containing ligands such as histidine, histamine, imidazole, iminodiacetic acid that readily form stable complexes with the tricarbonyl precursor have been extensively used for functionalization of various biomolecules in the recent years (Dumas et al., 2001; Du et al., 2001; Blauenstein et al., 2001; Schibli et al., 2001). Here, we report the work carried out on complexation studies of histidine functionalized VIP analogues via tricarbonyl synthon and bioevaluation to explore their potential as tumor imaging agents. ARTICLE IN PRESS www.elsevier.com/locate/apradiso 0969-8043/$ - see front matter r 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.apradiso.2006.11.001 Ã Corresponding author. Tel.: +91 22 2559 3676; fax: +91 22 2550 5345. E-mail address: meerav@barc.gov.in (M. Venkatesh).