A targeted low molecular weight near-infrared fluorescent probe for prostate cancer

Liu, Tiancheng; Wu, Lizhong; Hopkins, Mark R.; Choi, Joseph K.; Berkman, Clifford E.

doi:10.1016/j.bmcl.2010.09.057

Cited by 57 publications

(44 citation statements)

References 31 publications

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“…Humblet and colleagues synthesized the first phosphoramidate-IRDye78 (GPI-78) conjugate with a binding affinity at K i = 9 nmol/L, but GPI-78 was cleared too fast from the body, and imaging had to be performed 20 seconds postinjection resulting in very low tumor signals (20). Liu and colleagues reported a Cy5.5-labeled phosphoramidate peptidomimetic PSMA ligand Cy5.5-CTT-54.2 with IC 50 at 0.55 nmol/L (42). This probe demonstrated the ability to specifically label PSMA-positive prostate cancer cells, but no further in vivo imaging data were reported.…”

Section: Discussionmentioning

confidence: 99%

Development of Targeted Near-Infrared Imaging Agents for Prostate Cancer

Wang

Huang

Heston

et al. 2014

Molecular Cancer Therapeutics

102

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Prostate cancer is the most common noncutaneous malignancy affecting men in North America. Radical prostatectomy remains a definitive treatment for prostate cancer. However, prostate surgeries are still performed “blindly” with the extent of tumor infiltration past the margins of the surgery only being determined postoperatively. An imaging modality that can be used during surgery is needed to help define the tumor margins. With its abundant expression in prostate cancer, prostate-specific membrane antigen (PSMA) is an ideal target for detection of prostate cancer. The purpose of this study was to develop PSMA-targeted near-infrared (NIR) optical imaging probes for intraoperative visualization of prostate cancer. We synthesized a high-affinity PSMA ligand (PSMA-1) with low molecular weight and further labeled it with commercially available NIR dyes IRDy800 and Cy5.5. PSMA-1 and PSMA-1–NIR conjugates had binding affinities better than the parent ligand Cys-CO-Glu. Selective binding was measured for each of the probes in both in vitro and in vivo studies using competitive binding and uptake studies. Interestingly, the results indicated that the pharmacokinetics of the probes was dependent of the fluorophore conjugated to the PSMA-1 ligand and varied widely. These data suggest that PSMA-targeted probes have the potential to be further developed as contrast agents for clinical intraoperative fluorescence-guided surgery.

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Section: Discussionmentioning

confidence: 99%

Development of Targeted Near-Infrared Imaging Agents for Prostate Cancer

Wang

Huang

Heston

et al. 2014

Molecular Cancer Therapeutics

102

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“…Recently, the successful deployment of PSMA inhibitors as targeting motifs for imaging and therapeutic agents suggests that such constructs can serve as pharmacokinetic alternatives to antibodies (25)(26)(27)(28)(29)(30). These studies also support the concept that such compounds may also be applied as diagnostic and therapeutic agents targeted to PSMA-positive (PSMA+) tumor-associated vasculatures of various non-prostatic tumors.…”

Section: Introductionmentioning

confidence: 99%

Detection of prostate-specific membrane antigen on HUVECs in response to breast tumor-conditioned medium

Liu

Jabbes

Nedrow³

et al. 2011

Int J Oncol

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Abstract. Prostate-specific membrane antigen (PSMA), a well-known biomarker of prostate cancer, has also been found to be highly expressed in the neovasculature of multiple non-prostatic solid tumors. As a consequence, it has the potential to become a biomarker for tumor-associated vasculature. Herein, we describe an in vitro model for assessing PSMA expression associated with tube formation by primary human umbilical vein endothelial cells (HUVECs) cultured in Matrigel and induced by tumor-conditioned medium (TCM) derived from human breast cancer cells (MDA-MB-231). In contrast to vascular endothelial growth factor (VEGF)-containing endothelial cell medium, TCM induced higher expression of PSMA in HUVECs. The vessel-like tubes were detected by imaging with fluorescent PSMA inhibitors. Consequently, this in vitro model is expected to enable subsequent studies aimed at determining the role of PSMA in angiogenesis and factors that induce it.

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“…23 As a consequence, enzyme inhibitors have been developed to selectively, and in some cases, irreversibly bind to PSMA. [24][25][26][27] Most recently, our lab developed, and radiolabeled with 18 F, the phosphoramidate inhibitors 5 and 6 ( Fig. 1), which exhibits both high selectivity for PSMA-positive tumors and rapid clearance in vivo.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and evaluation of constrained phosphoramidate inhibitors of prostate-specific membrane antigen

Ley

Beattie

Dannoon

et al. 2015

Bioorganic & Medicinal Chemistry Letters

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Prostate-specific membrane antigen (PSMA) is a cell-surface enzyme-biomarker that is actively pursued for targeted delivery of imaging and therapeutic agents for prostate cancer. Our lab has developed PSMA inhibitors based on a phosphoramidate scaffold, which has shown both high selectivity for PSMA-positive tumors and rapid clearance in vivo when radiolabeled with (18)F. However, this scaffold exhibits hydrolytic instability under low pH and high temperature conditions, barring the use of other imaging or therapeutic radionuclides such as (68)Ga or (177)Lu. Previous studies in our lab have shown a trend in increasing acid stability as the distance between the phosphoramidate core and the α-carboxylate of the P1 residue is increased. Therefore, a new generation of phosphoramidate inhibitors was developed based on trans-4-hydroxyproline as the P1 residue to restrict the interaction of the α-carboxylate to the phosphoramidate core. These hydroxyproline inhibitors demonstrated comparable IC50 values to earlier generations as well as enhanced thermal and acid stability.

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A targeted low molecular weight near-infrared fluorescent probe for prostate cancer

Cited by 57 publications

References 31 publications

Development of Targeted Near-Infrared Imaging Agents for Prostate Cancer

Development of Targeted Near-Infrared Imaging Agents for Prostate Cancer

Detection of prostate-specific membrane antigen on HUVECs in response to breast tumor-conditioned medium

Synthesis and evaluation of constrained phosphoramidate inhibitors of prostate-specific membrane antigen

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