Novel Receptor-Targeted Fluorescent Contrast Agents for In Vivo Tumor Imaging

Achilefu, Samuel; Dorshow, Richard B.; Bugaj, Joseph E.; Rajagopalan, Raghavan

doi:10.1097/00004424-200008000-00004

Cited by 313 publications

(238 citation statements)

References 28 publications

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“…These non-ABI-specific probes were not retained in the A549 tumor tissue, but predominantly accumulated in the liver within 1 h after infection of the probes. This distribution is similar to the hepatobiliary excretion pathway observed in normal rats (21) and in humans using ICG (48).…”

Section: A549 Tumor Cells Express Abisupporting

confidence: 83%

“…The linear peptides were prepared by standard fluorenylmethyl (Fmoc) protocol (25), as described (21,23). Conjugation of Cypate with peptides was performed on solid support.…”

Section: Synthesis Of Nir Fluorescent Molecular Probe (Cypate)mentioning

confidence: 99%

“…One motif is a NIR carbocyanine fluorescent probe (Cypate) that is currently used to develop bioactive optical contrast agents (21), and the other is a linear hexapeptide (GRDSPK, abbreviated GRD) derived from the ABI-avid heptapeptide GRGDSPK (22) but lacking the RGD sequence. Intuitively, deletion of glycine in the linear RGD heptapeptide would be expected to diminish or eradicate the binding of the resulting GRD peptide to ABI because of alteration in the interatomic distances between the arginine and aspartic acid binding groups.…”

mentioning

confidence: 99%

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Synergistic effects of light-emitting probes and peptides for targeting and monitoring integrin expression

Achilefu

Bloch²,

Markiewicz³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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119

113

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mouse ͉ optical imaging ͉ RGD peptides ͉ tumor ͉ near-infrared A ngiogenesis, the formation of new blood vessels, is the cardinal feature of virtually all malignant tumors (1). Because of this commonality, probing tumor-induced angiogenesis and associated proteins is a viable approach to detect and treat a wide range of cancers. Angiogenesis is stimulated by integrins, a large family of transmembrane proteins that mediate dynamic linkages between extracellular adhesion molecules and the intracellular actin skeleton. Integrins are composed of two different subunits, ␣ and ␤, which are noncovalently bound into ␣␤ complexes (2-4). Particularly, the expression of ␣ v ␤ 3 integrin (ABI) in tumor cells undergoing angiogenesis and on the epithelium of tumor-induced neovasculature alters the interaction of cells with the extracellular matrix, thereby increasing tumorigenicity and invasiveness of cancers (5-9).Numerous studies have shown that ABI and more than seven other heterodimeric integrins recognize proteins and low molecular weight ligands containing RGD (arginine-glycineaspartic acid) motifs in proteins and small peptides (10). Based on structural and bioactivity considerations, cyclic RGD peptide ligands are preferentially used as delivery vehicles for molecular probes for imaging (8,(11)(12)(13) and treating (14-17) ABI-positive tumors and proliferating blood vessels. Until recently, most of the in vivo imaging studies were performed with radiopharmaceuticals because of the high sensitivity and clinical utility of nuclear imaging methods. Particularly, the use of small monoatomic radioisotopes does not generally interfere with the biodistribution and bioactivity of ligands. Despite these advantages, nuclear imaging is currently only performed in specialized centers because of regulatory, production, and handling issues associated with radiopharmaceuticals. Optical imaging is an alternative but complementary method to interrogate molecular processes in vivo and in vitro.Optical imaging for biomedical applications typically relies on activating chromophore systems with low energy radiation between 400 -and 1,500-nm wavelengths and monitoring the propagation of light in deep tissues with a charge-coupled device camera or other point source detectors (18). Molecular optical imaging of diseases with molecular probes is attractive because of the flexibility of altering the detectable spectral properties of the probes, especially in the fluorescence detection mode. The probes can be designed to target cellular and molecular processes at functional physiological concentrations. For deep-tissue imaging, molecular probes that are photoactive in the near-infrared (NIR) instead of visible wavelengths are preferred to minimize background tissue autof luorescence and light attenuation caused by absorption by intrinsic chromophores (19). In contrast to radioisotopes, the NIR antennas are usually large heteroatomic molecules that could impact the biodistribution and activity of conjugated bioactive ligands. However, previous s...

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Section: A549 Tumor Cells Express Abisupporting

confidence: 83%

“…The linear peptides were prepared by standard fluorenylmethyl (Fmoc) protocol (25), as described (21,23). Conjugation of Cypate with peptides was performed on solid support.…”

Section: Synthesis Of Nir Fluorescent Molecular Probe (Cypate)mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Synergistic effects of light-emitting probes and peptides for targeting and monitoring integrin expression

Achilefu

Bloch²,

Markiewicz³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

119

113

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“…A variety of reporter probes have been used for enhanced detection of early cancers, including somatostatin receptor-targeted probes [32][33][34], folate receptor-targeted agents [35], tumor cell-targeted agents [36][37][38][39], agents that incorporate into areas of calcification, bone formation or both [40], and agents being activated by tumor-associated proteases [41][42][43]. Many of these agents accumulate in (and thus enhance) tumors to a certain degree; however, FRET-based agents can yield particularly high tumor/background signal ratios because of their nondetectability in the native state.…”

Section: Detecting Early Cancersmentioning

confidence: 99%

Shedding light onto live molecular targets

Weissleder

Ntziachristos

2003

Nat Med

1,773

1,319

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Abstract-Optical sensing of specific molecular targets and pathways deep inside living mice has become possible as a result of a number of advances. These include design of biocompatible near-infrared fluorochromes, development of targeted and activatable 'smart' imaging probes, engineered photoproteins and advances in photon migration theory and reconstruction. Together, these advances will provide new tools making it possible to understand more fully the functioning of protein networks, diagnose disease earlier and speed along drug discovery.

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“…Larger molecules, such as antibodies, can elicit an adverse immune response from the host animal, and their long half-life in the blood results in high background fl uorescence and long clearance times [16] and [17]. In addition, large biomolecules are often taken up preferentially by the liver, precluding imaging of liver-proximal organs [18]. Finally, for the contrast agent to effectively penetrate to the target site, it must diffuse from the vasculature to the site of the pathology; larger molecules show very poor diffusion characteristics which may prevent them from reaching the target site [19].…”

Section: Antibody Conjugatesmentioning

confidence: 99%

A systematic approach to the development of fluorescent contrast agents for optical imaging of mouse cancer models

Kovar

Simpson

Schutz-Geschwender

et al. 2007

Analytical Biochemistry

141

142

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Novel Receptor-Targeted Fluorescent Contrast Agents for In Vivo Tumor Imaging

Abstract: Optical detection of tumors with a receptor-targeted fluorescent contrast agent has been demonstrated. This result represents a new direction in cancer diagnosis and patient management.

Cited by 313 publications

References 28 publications

Synergistic effects of light-emitting probes and peptides for targeting and monitoring integrin expression

Synergistic effects of light-emitting probes and peptides for targeting and monitoring integrin expression

Shedding light onto live molecular targets

A systematic approach to the development of fluorescent contrast agents for optical imaging of mouse cancer models

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