Detection of Colon Cancer with^99mTc-Labeled Bombesin Derivative (^99mTc-leu13-BN1)

Abstract

Breast, prostate, and lung cancer have been successfully detected with 99mTc bombesin (99mTc-leu13-BN1), the radiopharmaceutical that our group developed from synthesis to diagnostic trials. Overexpression of bombesin receptors (BNRs) in colon cancer is well known: the aim of this study was to assess whether or not colon cancer can be detected with a 99mTc-leu13-BN1 scan. Thirteen (13) patients, 7 of whom with known rectal cancer and 6 scheduled to undergo endoscopic removal of polyps for suspicion of colon cancer, were studied with a 99mTc-leu13-BN1 scan. Dynamic, single photon emission computed tomography, and whole-body scans were performed within 1 hour, before discharge of radioactivity from the liver into the duodenum. Sixteen (16) of 17 colorectal cancer locations were detected with a 99mTc-leu13-BN1 scan with 94.1% sensitivity. Six (6) lesions were benign: 1 Crohn's disease, 1 polyp with mild dysplasia, 4 polyps with simple hyperplasia; 99mTc-leu13-BN1 scans were positive in two nontumoral lesions, Crohn's disease, and mild dysplasia and true negative in 4: specificity was 67%. Of the 7 patients with known rectal cancer, 5, who underwent operations instead of radiation therapy, showed lymph-node invasion on 99mTc-leu13-BN1 scans. Operations confirmed the scintigraphic staging. 99mTc-leu13-BN1 is taken up by colon cancer. Scans are sensitive, although scarcely specific. 99mTc-leu13-BN1 allows for node-invasion detection.

International Union of Pharmacology. LXVIII. Mammalian Bombesin Receptors: Nomenclature, Distribution, Pharmacology, Signaling, and Functions in Normal and Disease States

“…This observation has led to considerable interest in the possibility of developing radiolabeled analogs of Bn that could be use for localization of the tumors containing Bn receptors or the development of radiolabeled Bn analogs or Bn analogs coupled to cytotoxic agents that could be used to treat tumors overexpressing Bn receptors through bombesin receptor-mediated cytotoxicity (Breeman et al, 2002;de Jong et al, 2003;Cornelio et al, 2007;de Visser et al, 2007a Tc) GRP analogs with enhanced stability that bind with high affinity to BB 2 receptors have been reported, as well as their ability to image various human tumors in vivo using gamma detectors or positron emission tomography (Breeman et al, 2002;Nock et al, 2003;Smith et al, 2003Smith et al, , 2005Johnson et al, 2006;Lantry et al, 2006;Zhang et al, 2006Zhang et al, , 2007ade Visser et al, 2007a;DimitrakopoulouStrauss et al, 2007;Garrison et al, 2007;Parry et al, 2007;Prasanphanich et al, 2007;Waser et al, 2007). In some preliminary studies in humans, tumors were imaged in the majority of patients, and in some cases, tumors that were not seen with other commonly used imaging modalities were detected using radiolabeled Bn analogs Scopinaro et al, 2004Scopinaro et al, , 2005Dimitrakopoulou-Strauss et al, 2007). At present no study has established the value of imaging using radiolabeled Bn analogs.…”

177Lu-AMBA Biodistribution, Radiotherapeutic Efficacy, Imaging, and Autoradiography in Prostate Cancer Models with Low GRP-R Expression

“…Expression of the receptor is not normally seen in the epithelium of the prostate, colon, or lung (3,6). GRP-R is ectopically expressed in many human cancers, including breast, colon, and prostate, and regulates cell proliferation, differentiation, and morphology (7)(8)(9)(10). Elevated GRP-R expression is not confined to invasive prostate cancer but is also present in prostatic intraepithelial neoplasia, which may be an early indicator of cancer (10).…”

In vitro binding evaluation of 177Lu-AMBA, a novel 177Lu-labeled GRP-R agonist for systemic radiotherapy in human tissues

“…Radiolabeled AMBA ( 177 Lu-AMBA), where AMBA = DO 3 A-CH 2 CO-Gly-4-aminobenzoyl-Gln-Trp-Ala-ValGly-His-Leu-Met-NH 2 was labeled in-house to a specific activity of 3.0 Ci/lmole with an RCP of C95% [22]. 175 Lu-AMBA (Lu-AMBA) was synthesized and HPLC purified in-house.…”

“…When aberrantly expressed as a functional protein in cancer cells, GRP-R activation regulates tumor cell morphology, differentiation and proliferation. The GRP and NMB receptors are expressed in a variety of tumor tissues, including primary and metastatic tumors from prostate [11,[14][15][16] breast [17][18][19][20][21] and colon [22]. High expression of GRP-R was demonstrated on primary breast and prostate cancer tissue samples using in situ hybridization, immunohistochemistry and radio-ligand binding assays.…”