Diagnostic efficacy and safety of<sup>99m</sup>Tc-Labeled monoclonal antibody ior c5 in patients with colorectal and anal carcinomas: Final report clinical trial phase I/II

Ramos-Suzarte, Mayra; Pintado, Alejandro Perera; Mesa, Nelson Rodríguez; Oliva, J; Iznaga-Escobar, Normando; Aroche, Leonel T; Pimentel, Gilmara; González, Joaquín V.; Cordero, Maria; Rodríguezi, Obaya T; Crombet, Ramos T; Pérez, Rodríguez R

doi:10.4161/cbt.6.1.3552

Cited by 10 publications

(6 citation statements)

References 6 publications

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“…SPECT imaging with 99m Tc-TCP-1 may offer unique features relative to other CRC imaging methods such as immunoscintigraphy and 18 F-FDG PET imaging in discriminating early CRC lesions from inflammatory tissues [9]. Although radiolabeled antibodies or antibody fragments can target CRC primary tumor sites and metastases with high specificity and good predictive value [35–37], there are drawbacks to the use of antibodies, including cost, immune response on repeat administration, suboptimal pharmacokinetics, and hepatobiliary excretion that results in high radioactive background in the intestine [35]. Some of these disadvantages can be overcome by using engineered or humanized antibody fragments.…”

Section: Discussionmentioning

confidence: 99%

Characterization of TCP-1 probes for molecular imaging of colon cancer

Liu

Gray

Barber

et al. 2016

Journal of Controlled Release

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Molecular probes capable of detecting colorectal cancer (CRC) are needed for early CRC diagnosis. The objective of this study was to characterize c[CTPSPFSHC]OH (TCP-1), a small peptide derived from phage display selection, for targeting human CRC xenografts using technetium-99m (99mTc)-labeled TCP-1 and fluorescent cyanine-7 (Cy7)-labeled form of the peptide (Cy7-TCP-1). 99mTc-TCP-1 was generated by modifying TCP-1 with succinimidyl-6-hydrazino-nicotinamide (S-HYNIC) followed by radiolabeling. In vitro saturation binding experiments were performed for 99mTc-TCP-1 in human HCT116 colon cancer cells. SCID mice with human HCT116 cancer xenografts were imaged with 99mTc-TCP-1 or control peptide using a small-animal SPECT imager: Group I (n=5) received no blockade; Group II (n=5) received a blocking dose of non-radiolabeled TCP-1. Group III (n=5) were imaged with 99mTc-labeled control peptide (inactive peptide). SCID mice with human PC3 prostate cancer xenografts (Group IV, n=5) were also imaged with 99mTc-TCP-1. Eight additional SCID mice bearing HCT116 xenografts in dorsal skinfold window chambers (DSWC) were imaged by direct positron imaging of 18F-fluorodeoxyglucose (18F-FDG) and fluorescence microscopy of Cy7-TCP-1. In vitro 99mTc-HYNIC-TCP-1 binding assays on HCT 116 cells indicated a mean Kd of 3.04 ± 0.52 nM. In cancer xenografts, 99mTc-TCP-1 radioactivity (%ID/g) was 1.01±0.15 in the absence of blockade and was reduced to 0.26±0.04 (P < 0.01) with blockade. No radioactive uptake was observed in the PC3 tumors with 99mTc-TCP-1 or HCT116 tumors with inactive peptide. Cy7-TCP-1 activity localized not only in metabolically active tumors, as defined by 18F-FDG imaging, but also in peritumoral microvasculature. In conclusion, TCP-1 probes may have a distinct targeting mechanism with high selectivity for CRC and tumor-associated vasculature. Molecular imaging with TCP-1 probes appears promising to detect malignant colorectal lesions.

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Section: Discussionmentioning

confidence: 99%

Characterization of TCP-1 probes for molecular imaging of colon cancer

Liu

Gray

Barber

et al. 2016

Journal of Controlled Release

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“…In direct method, the use of reducing agents such as Sn (P) can produce 99m Tc intermediates that form unstable complexes with peptides. 25 In ligand exchange method, 99m Tc-chelate intermediate allowed to react to peptides under mild conditions to form final acceptable radiolabeled peptides. 26 For optimizing labeling, in direct method, the influence of pH (changing buffers from acidic to alkaline), concentration of SnCl 2 and temperature was investigated on radiochemical yield.…”

Section: Discussionmentioning

confidence: 99%

Optimizing Labeling Conditions for Cysteine-Based Peptides with^99mTc

Sabahnoo¹,

Hosseinimehr²

2016

Journal of the Brazilian Chemical Society

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Radiolabelled peptides have attracted a great deal of attention due to their wide applicability in the development of target-specific radiopharmaceuticals. They can easily be used in diagnostic imaging as carriers for the delivery of radionuclides to tumors as well as for therapy. Previous investigations revealed that technetium(V) could form stable complexes with peptide-based ligands of N 3 S type such as Cys-Gly-Gly-Gly. Herein, a targeting HER-2 receptor peptide was labeled with technetium-99m ( 99m Tc) with two different types of tetrapeptide-based ligands, Cys-Gly-Gly-Gly and Cys-Ser-Ser-Ser. The effect of experimental parameters in the labeling procedure such as type of buffer solutions, pH of media, and type of exchange ligands were optimized toward obtaining maximum labeling yield. The optimum labeling conditions were different for two peptides. Shelf life of both labeled peptides was determined by analytical reversed-phase high-performance liquid chromatography (RP-HPLC) and thin layer chromatography (TLC) that showed radiochemical yield up to 95% even after 4 h.

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“…This antigen is a cell surface Olinked glycoprotein carbohydrate chain very limited in most normal tissues and heterogeneously expressed in a variety of human malignancies such as ovary, breast, uterus, and lung tumors, although it was mostly evidenced in colorectal tumors [12,32]. In primary and metastatic colorectal carcinomas as well as in ovarian adenocarcinomas, these results were confirmed by immunoscintigraphy technique with ior C5 Mab labeled with 99mTc-labeled [13][14][15][16][17]33].…”

Section: Discussionmentioning

confidence: 99%

“…This TAA was demonstrated in these malignancies using the ior C5 Mab, a highly specific IgG1 against ior C2 antigen, by means of immunohistochemical methods [11,12]. Additionally, immunoscintigraphy with 99mTc-labeled Mab ior C5 has been considered a useful procedure for the diagnosis and followup of the patients with colorectal tumors, its metastasis, and recurrences [13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Tumor Expression of the Carcinoembryonic Antigen Correlates with High Mitotic Activity and Cell Pleomorphism Index in Lung Carcinoma

Blanco

Rengifo²,

Cedeño³

et al. 2013

Journal of Histology

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At present, some research efforts are focusing on the evaluation of a variety of tumor associated antigens (TAAs) for a better understanding of tumor biology and genetics of lung tumors. For this reason, we evaluated the tissue expression of carcinoembryonic antigen (CEA) and ior C2 (a cell surface O-linked glycoprotein carbohydrate chain TAA) in lung carcinomas, as well as its correlation with a variety of clinicopathological features. The tissue expression of CEA was evidenced in 22/43 (51.16%) lung carcinomas and it was correlated with mitotic activity, cell pleomorphism indexes, and age of patients. The expression of ior C2 was observed in 15/43 (34.88%) tumors but no correlation with the clinicopathological features mentioned above was obtained. No correlation between both CEA and ior C2 antigens expression and the overall survival (OS) of non-small-cell lung cancer patients was also observed. However, CEA-negative patients displayed higher OS rates as compared with positive ones (69.74 versus 58.26 months). Our results seem to be in agreement with the role of CEA expression in tumor cell proliferation, inhibition of cell polarizations and tissue architecture distortion. The significance of ior C2 antigen in these malignancies and it potential use in diagnosis, prognosis, and/or immunotherapy must be reevaluated.

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Diagnostic efficacy and safety of^99mTc-Labeled monoclonal antibody ior c5 in patients with colorectal and anal carcinomas: Final report clinical trial phase I/II

Cited by 10 publications

References 6 publications

Characterization of TCP-1 probes for molecular imaging of colon cancer

Characterization of TCP-1 probes for molecular imaging of colon cancer

Optimizing Labeling Conditions for Cysteine-Based Peptides with^99mTc

Tumor Expression of the Carcinoembryonic Antigen Correlates with High Mitotic Activity and Cell Pleomorphism Index in Lung Carcinoma

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Diagnostic efficacy and safety of99mTc-Labeled monoclonal antibody ior c5 in patients with colorectal and anal carcinomas: Final report clinical trial phase I/II

Cited by 10 publications

References 6 publications

Characterization of TCP-1 probes for molecular imaging of colon cancer

Characterization of TCP-1 probes for molecular imaging of colon cancer

Optimizing Labeling Conditions for Cysteine-Based Peptides with99mTc

Tumor Expression of the Carcinoembryonic Antigen Correlates with High Mitotic Activity and Cell Pleomorphism Index in Lung Carcinoma

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Product

Resources

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Diagnostic efficacy and safety of^99mTc-Labeled monoclonal antibody ior c5 in patients with colorectal and anal carcinomas: Final report clinical trial phase I/II

Optimizing Labeling Conditions for Cysteine-Based Peptides with^99mTc