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

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

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)223-230
Number of pages8
JournalJournal of Controlled Release
Volume239
DOIs
StatePublished - Oct 10 2016

Fingerprint

Molecular Imaging
Colonic Neoplasms
Heterografts
Colorectal Neoplasms
Peptides
SCID Mice
Fluorodeoxyglucose F18
Neoplasms
HCT116 Cells
Molecular Probes
Technetium
Microvessels
Single-Photon Emission-Computed Tomography
Early Detection of Cancer
Fluorescence Microscopy
Bacteriophages
Radioactivity
Prostatic Neoplasms
Electrons

Keywords

  • Tc
  • Colorectal cancer
  • Molecular imaging
  • Mouse xenograft models
  • Peptide
  • SPECT

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Characterization of TCP-1 probes for molecular imaging of colon cancer. / Liu, Zhonglin; Gray, Brian D.; Barber, Christy; Bernas, Michael J; Cai, Minying; Furenlid, Lars R; Rouse, Andrew R; Patel, Charmi; Banerjee, Bhaskar; Liang, Rongguang; Gmitro, Arthur F; Witte, Marlys H; Pak, Koon Y.; Woolfenden, James M.

In: Journal of Controlled Release, Vol. 239, 10.10.2016, p. 223-230.

Research output: Contribution to journalArticle

@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 = "Tc, Colorectal cancer, Molecular imaging, Mouse xenograft models, Peptide, SPECT",
author = "Zhonglin Liu and Gray, {Brian D.} and Christy Barber and Bernas, {Michael J} and Minying Cai and Furenlid, {Lars R} and Rouse, {Andrew R} 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.}",
year = "2016",
month = "10",
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",

}

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 J

AU - Cai, Minying

AU - Furenlid, Lars R

AU - Rouse, Andrew R

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 - Tc

KW - Colorectal cancer

KW - Molecular imaging

KW - Mouse xenograft models

KW - Peptide

KW - SPECT

UR - http://www.scopus.com/inward/record.url?scp=84984993617&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84984993617&partnerID=8YFLogxK

U2 - 10.1016/j.jconrel.2016.08.033

DO - 10.1016/j.jconrel.2016.08.033

M3 - Article

VL - 239

SP - 223

EP - 230

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

ER -