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[111In]-DOTA-Aminohexanoyl-[D-Phe6,Leu-NHCH2CH2CH313,desMet14] BBN[6-14].


Chopra A.


Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2010 May 20 [updated 2010 Jul 08].


The gastrin-releasing peptide (GPR), a bombesin (BBN) analog that targets the GRP receptor (GRP-R) to mediate its activity, is believed to assist in the progression and metastases of a variety of human cancers by acting as a growth factor (1, 2). Also, because the overexpression of GRP-R has been documented for many cancers, this receptor has been targeted with radiopharmaceuticals for the treatment of different malignancies, including that of the prostate (1). For a satisfactory therapeutic response with radiochemicals such as radiolabeled GRP, BBN, or their analogs, an optimal cellular accumulation of the radionuclide is necessary, and the uptake process is mediated by endocytosis, resulting in internalization of the receptor-ligand (RL) complex (3). Because the RL complex internalization is upregulated by the interaction of an agonist with its receptor, investigators in the field developed different radiolabeled BBN analogs that were GRP-R agonists and evaluated their biological characteristics under in vitro and in vivo conditions (3). Results obtained from several such studies showed that, in general, cellular uptake of the respective labeled agonists was low due to low affinity and binding to the receptor, and these compounds behaved more like antagonists rather than agonists (3). Compared to the agonists, compounds with antagonist activity are known to have a higher affinity for the receptor, can block the effects of an agonist, do not accelerate receptor internalization, and are now increasingly used for diagnostic purposes (3). Many BBN analogs have been synthesized, and studies for their affinity to the GRP-R are described elsewhere (3). From these studies it was concluded that modifications at the C-terminus of BBN yielded compounds with agonistic properties that resulted in increased binding, but reduced internalization of the compound (3). Therefore, the C-terminal–modified BBN analogs were suitable for cancer diagnosis applications. Nock et al. developed a 99mTc-labeled GRP-R antagonist, Demobesin 1, and investigated its biodistribution and use as an imaging agent for GRP-R–expressing tumors in nude mice (4) (Demobesin 1 is an N-terminal modified BBN analogue structurally based on a potent GRP-R antagonist; this agent has been discussed separately in MICAD, (5)). Although very low cellular internalization of [99mTc]-Demobesin 1 was observed, it showed a high tumor accumulation with a long duration, suggesting that the labeled compound was suitable for diagnostic imaging. Similar results were also obtained with other 99mTc-labeled N-terminal derivatives of BBN ([99mTc]-Demobesin 3 and 4) as described elsewhere (6, 7). As an alternative to the existing compounds, another C-terminal–modified, 111In-labeled GRP-R antagonist BBN analog, [111In]-DOTA-aminohexanoyl-[D-Phe6,Leu-NHCH2CH2CH313,desMet14] BBN[6-14] ([111In]bomproamide) was synthesized, and its biodistribution was studied in normal mice by Abd-Elgaliel et al. (3). The radiochemical was also evaluated for its imaging properties with single-photon emission tomography/computed tomography (SPECT/CT) in mice bearing tumors derived from PC-3 cells, which are of human prostate cancer origin and have a high level of GRP-R expression.

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