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

Zhonglin Liu; Brian D. Gray; Christy Barber; Michael Bernas; Minying Cai; Lars R. Furenlid; Andrew Rouse; Charmi Patel; Bhaskar Banerjee; Rongguang Liang; Arthur F. Gmitro; Marlys H. Witte; Koon Y. Pak; James M. Woolfenden

doi:10.1016/j.jconrel.2016.08.033

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

Zhonglin Liu, Brian D. Gray, Christy Barber, Michael Bernas, Minying Cai, Lars R. Furenlid, Andrew Rouse, Charmi Patel, Bhaskar Banerjee, Rongguang Liang, Arthur F. Gmitro, Marlys H. Witte, Koon Y. Pak, James M. Woolfenden

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9 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	223-230
Number of pages	8
Journal	Journal of Controlled Release
Volume	239
DOIs	https://doi.org/10.1016/j.jconrel.2016.08.033
State	Published - Oct 10 2016

Keywords

Colorectal cancer
Molecular imaging
Mouse xenograft models
Peptide
SPECT
Tc

ASJC Scopus subject areas

Pharmaceutical Science

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10.1016/j.jconrel.2016.08.033

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@article{4feb3cf2a8e0448fa1fed59280d56f94,

title = "Characterization of TCP-1 probes for molecular imaging of colon cancer",

abstract = "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.",

keywords = "Colorectal cancer, Molecular imaging, Mouse xenograft models, Peptide, SPECT, Tc",

author = "Zhonglin Liu and Gray, {Brian D.} and Christy Barber and Michael Bernas and Minying Cai and Furenlid, {Lars R.} and Andrew Rouse and Charmi Patel and Bhaskar Banerjee and Rongguang Liang and Gmitro, {Arthur F.} and Witte, {Marlys H.} and Pak, {Koon Y.} and Woolfenden, {James M.}",

note = "Publisher Copyright: {\textcopyright} 2016 Elsevier B.V.",

year = "2016",

month = oct,

day = "10",

doi = "10.1016/j.jconrel.2016.08.033",

language = "English (US)",

volume = "239",

pages = "223--230",

journal = "Journal of Controlled Release",

issn = "0168-3659",

publisher = "Elsevier",

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TY - JOUR

T1 - Characterization of TCP-1 probes for molecular imaging of colon cancer

AU - Liu, Zhonglin

AU - Gray, Brian D.

AU - Barber, Christy

AU - Bernas, Michael

AU - Cai, Minying

AU - Furenlid, Lars R.

AU - Rouse, Andrew

AU - Patel, Charmi

AU - Banerjee, Bhaskar

AU - Liang, Rongguang

AU - Gmitro, Arthur F.

AU - Witte, Marlys H.

AU - Pak, Koon Y.

AU - Woolfenden, James M.

PY - 2016/10/10

Y1 - 2016/10/10

N2 - 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.

AB - 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.

KW - Colorectal cancer

KW - Molecular imaging

KW - Mouse xenograft models

KW - Peptide

KW - SPECT

KW - Tc

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U2 - 10.1016/j.jconrel.2016.08.033

DO - 10.1016/j.jconrel.2016.08.033

M3 - Article

C2 - 27574992

AN - SCOPUS:84984993617

SN - 0168-3659

VL - 239

SP - 223

EP - 230

JO - Journal of Controlled Release

JF - Journal of Controlled Release

ER -

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

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