TWI827888B - Cd166-targeted synthesized peptides, compositions and contrast agents thereof - Google Patents

Abstract

Disclosed herein are CD166-targeted synthesized peptides, compositions and contrast agents. The synthesized peptides is capable of binding to cancer stem cells that exhibit CD166 cell markers, and accumulate in tumor, so that the synthesized peptides have potential for use as nuclear imaging agent for diagnosis.

Description

CD166 Target synthetic peptides, compositions and contrast agents

The present invention relates to the field of radiological medical imaging and diagnosis, and in particular to a synthetic peptide capable of detecting the CD166 target.

Many studies believe that there is a small number of cancer stem cells in tumor tissue. These cells are resistant to radiation or chemotherapy. When most of the tumor cells die due to treatment, a small number of cancer stem cells will hide, differentiate, and proliferate. , leading to tumor recurrence. If the status or location of cancer stem cells cannot be accurately tracked or assessed, early treatment will not be available, causing cancer patients' condition to worsen again.

CD166 is a specific antigen protein on the surface of colorectal cancer stem cells (CRCSCs). If early-stage colorectal cancer can be treated early before the cancer spreads, the five-year survival rate is as high as 90%. According to research, only one-third of patients are discovered before metastasis occurs. If lymphatic metastasis occurs, the survival rate can be as high as 90% in five years. The survival rate is only about 50%; once there is metastasis to other distant organs, the five-year survival rate is less than 10%. Clinically, rectal cancer is generally found to recur after treatment with chemotherapy drugs. The reason is that there are cancer stem cells in the tumor tissue. Clinically, there are currently drugs related to the treatment of cancer stem cells. However, there is no effective method to accurately detect the presence of cancer stem cells in the lesion or within the individual. Therefore, Inability to provide effective treatment results in tumor recurrence. In view of this, there is an urgent need in the art for a novel composition for detecting cancer stem cells to improve the shortcomings of the prior art.

In order to allow readers to understand the basic meaning of the disclosure, this Summary provides a brief description of the disclosure. The Summary of the Invention is not a complete description of the present disclosure, and is not intended to define the technical features or rights scope of the present invention.

One aspect of the present invention relates to a CD166-targeted synthetic peptide. The synthetic peptide includes a binding peptide and an additional peptide, wherein the synthetic peptide is selected from the group consisting of: SEQ ID NO: 1 ( EGHCNNQICSNQ), sequence number 2 (ETETQGTVCGGC), sequence number 3 (KCDNGTVACNQT), sequence number 4 (DNKCSNTAQTNG), sequence number 5 (HQHGNNTIGGN), sequence number 6 (DSEGNSNLCSQS), sequence number 7 (KGRPQSTMPNSQ) and sequence number 8 (DNESSTNITQTS ), and the additional peptide is connected to the binding peptide, which has the amino acid sequence of sequence number 9 (G ₁₈ C).

According to a specific embodiment of the present invention, the binding peptide is the amino acid sequence of SEQ ID NO: 6 (DSEGNSNLCSQS).

Another aspect of the present invention relates to a composition that can bind to CD166, which includes the synthetic peptide shown in any of the above embodiments and a fluorescent label labeled on the synthetic peptide.

Another aspect of the present invention relates to a composition that can be bound to CD166. Structurally, the composition includes the synthetic peptide shown in any of the preceding embodiments, a metal chelating agent and a radionuclide. The metal chelating agent is coupled with the synthetic peptide, and the radionuclide is marked on the metal chelating agent.

In an optional embodiment, the metal chelating agent is selected from the group consisting of: 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, DOTA), 1,4,7-triazacyclononane-1,4,7-triacetic acid (1,4 ,7-triazacyclononane-1,4,7-triacetic acid, NOTA), 1,4,7-triazacyclononane-1,4-diacetic acid (1,4,7-triazacyclononane-1,4-diacetic acid acid (NODA) and diethylenetriaminepenta-acetic acid (DTPA).

In other optional embodiments, the radioactive nuclide species is selected from the group consisting of: Ga-66, Ga-67, Ga-68, Zr-89, Lu-177, In-111, I -123. In a specific embodiment, the radioactive nuclide is In-111, and the binding peptide is the amino acid sequence of SEQ ID NO: 6 (DSEGNSNLCSQS). According to one embodiment of the present invention, the metal chelating agent is DTPA.

Another aspect of the present invention relates to a contrast agent, including the composition described in any of the above embodiments; and a contrast excipient.

Those with ordinary knowledge in the technical field to which the present invention belongs can fully understand the central concept, the technical means adopted and various implementation aspects of the present invention by referring to the following embodiments.

In order to make the above and other objects, features, advantages and embodiments of the present invention more clearly understood, the drawings are described as follows: Figures 1A to 1C show CD166tp-G ₁₈ according to an embodiment of the present invention. C target shows the results of expressing CD166 colorectal cancer cells; Figure 2 shows the results of ^{the 111} In-DTPA-CD166tp-G ₁₈ C stability test according to one embodiment of the present invention; Figure 3A shows the results according to one embodiment of the present invention. The straight line graph of the tumor uptake results of ¹¹¹ In-DTPA-CD166tp-G ₁₈ C tumor animal model; Figure 3B is a competition test of ¹¹¹ In-DTPA-CD166tp-G ₁₈ C according to another embodiment of the present invention. The straight line graph of the tumor uptake results of the tumor animal model; Figure 4 is the straight line graph of the tissue biodistribution results of ¹¹¹ In-DTPA-CD166tp-G ₁₈ C in the tumor animal model according to one embodiment of the present invention; Figure 5 shows the ratio of tumor to muscle and blood in the tumor animal model of ¹¹¹ In-DTPA-CD166tp-G ₁₈ C shown in the embodiment of Figure 4.

In order to make the description of this disclosure more detailed and complete, illustrative text descriptions are provided below for the implementation aspects and specific examples of the present invention; however, the implementation aspects and specific examples of the present invention are not limited thereto.

Unless otherwise stated, the scientific and technical terms used in this specification have the same meanings as commonly understood and customary by those with ordinary knowledge in the art. Furthermore, nouns used in this specification include both singular and plural forms of the noun, unless otherwise specified.

As used in this specification, the word "about" generally means that the actual value is within plus or minus 10%, 5%, 1% or 0.5% of a specific value or range. The term "about" as used herein means that actual values fall within acceptable standard errors of the mean, as would be considered by one of ordinary skill in the art to which this invention pertains. Except for experimental exceptions, or unless otherwise expressly stated, it is understood that ranges, quantities, values and percentages used herein are modified by the word "about". Therefore, unless otherwise stated, the numerical values or parameters disclosed in this specification and the accompanying patent claims are approximate values and may be changed as required.

Unless otherwise specified, the "synthetic peptides" disclosed herein include a specific amino acid sequence that contains conservation modifications, that is, the substitution or substitution of amino acids does not affect the activity of the synthetic peptide, that is, the ability to bind to Cancer cells expressing CD166.

The term "individual" refers to an animal, including a human being, and is applicable to the animals for which the synthetic peptides, compositions or kits of the present invention are used. Unless otherwise stated, the term "individual" refers to both males and females.

In order to solve the problems of the prior art, the purpose of the invention is to provide a novel synthetic peptide for detecting cancer stem cells, which has high sensitivity, specificity and stability, and can accumulate in tumor tissue for a long time for at least 48 hours. , has the potential to be used as a molecular nuclear medicine diagnostic drug. Furthermore, the synthetic peptide proposed by the present invention can improve the shortcomings of the previous technology. It can accurately diagnose whether there are cancer stem cells in the tissue through nuclear medical imaging technology without using invasive treatment or diagnostic means, so that Individuals can get appropriate cancer treatment as early as possible.

Multiple embodiments are disclosed below to illustrate various implementation aspects of the present invention, so that those with ordinary knowledge in the technical field to which the present invention belongs can implement the technical content disclosed in the present invention based on the disclosure of this specification. Therefore, the embodiments disclosed below cannot be used to limit the scope of rights of the present invention. Furthermore, all documents cited in this specification are deemed to be fully cited and become part of this specification.

Experimental Example 1 Synthetic peptide of the present invention

The synthetic peptide of the present invention is synthesized by a chemical synthesis method, and its specific content is shown in Table 1:

Experimental Example 2 The synthetic peptide of the present invention can bind to cells expressing CD166

This experimental example uses flow cytometry to analyze whether the synthetic peptide can bind to CD166-positive colorectal cancer. In this example, CD166tp-G ₁₈ C was tested. Specifically, the CD166tp-G ₁₈ C of the present invention further extends the additional sequence G ₁₈ C at the C-terminus of CD166tp to obtain the amino acid sequence of SEQ ID NO: 11. The CD166tp-G ₁₈ C has a relatively long circulation period in the body. long.

3)。*P<0.05,vs(CD166^- HCT15)CD166tp-G₁₈C-FITC；#P<0.05,vs(CD166+ HCT15)CD166tp-G₁₈C-FITC。如第1A圖的結果顯示，在CD166⁺HCT15細胞中，CD166tp-G₁₈C-FITC螢光強度顯著增加，但並未發現於CD166^- HCT15細胞。在競爭試驗的結果中，以非螢光CD166tp-G₁₈C預處理的組別，CD166tp-G₁₈C-FITC在CD166⁺ HCT15細胞中結合能力顯著降低。利用免疫螢光分析進一步測定CD166⁺和CD166^- HCT15細胞中CD166tp-G₁₈C-FITC結合能力。螢光影像的結果顯示相較於CD166^- HCT15的結果，CD166⁺ HCT15 中CD166tp-G₁₈C-FITC結合能力增加(第1B圖)。進一步確認CD166tp-G₁₈C-FITC標的至CD166是否在CD166⁺ HCT15細胞的表面。CD166tp-G₁₈C和CD166蛋白交互作用的分析結果，請參見第1C圖。CD166⁺ HCT15和CD166^- HCT15細胞以CD166tp-G₁₈C-FITC(20μg/mL)處理1小時。收集上清液，以生物素化CD166多株抗體(2μg/mL)處理或未處理含streptavidin瓊膠珠(4℃隔夜)。以ELISA分析免疫沈澱物的螢光訊號。競爭抑制試驗以CD166tp-G₁₈C(20μg/mL)預處理。數據以mean±SD(n

3).*P<0.05表示。結果顯示依照免疫沈澱分析的結果，以CD166抗體進行測定，結果顯示透過與CD166蛋白的交互作用，CD166tp-G₁₈C-FITC能夠結合至CD16⁶⁺ HCT15細胞，但不能結合至CD166- HCT15細胞。且CD166tp-G₁₈C-FITC結合的增加，能夠被非螢光CD166tp-G₁₈C預處理所抑制。 Furthermore, in order to test the binding ability of CD166tp-G ₁₈ C, the specific implementation method is as follows. CD166-positive colorectal cancer cells (CD166 ⁺ HCT15 cells) and CD166-negative colorectal cancer cells (CD166 ^- HCT15 cells) were treated with CD166tp-G ₁₈ C (20 μg/mL) labeled with the fluorescent substance FITC (i.e., CD166tp-G ₁₈ C- FITC) for 1 hour. In the competition experiment, CD166 ⁺ HCT15 cells were pretreated with CD166tp-G ₁₈ C (20 μg/mL) for 1 hour and then treated with CD166tp-G ₁₈ C-FITC (20 μg/mL) for 1 hour. The results are shown in Figure 1A. Data are expressed as mean + SD (n

3). *P<0.05, vs (CD166 ^- HCT15) CD166tp-G ₁₈ C-FITC; #P < 0.05, vs (CD166 + HCT15) CD166tp-G ₁₈ C-FITC. As shown in Figure 1A, the fluorescence intensity of CD166tp-G ₁₈ C-FITC increased significantly in CD166 ⁺ HCT15 cells, but was not found in CD166 ^- HCT15 cells. In the results of the competition test, the binding ability of CD166tp-G ₁₈ C-FITC in CD166 ⁺ HCT15 cells was significantly reduced in the group pretreated with non-fluorescent CD166tp-G ₁₈ C. Immunofluorescence analysis was used to further determine the CD166tp-G ₁₈ C-FITC binding ability in CD166 ⁺ and CD166 ⁻ HCT15 cells. The results of fluorescence imaging showed that compared with the results of CD166 ^- HCT15, CD166tp-G ₁₈ C-FITC binding capacity was increased in CD166 ⁺ HCT15 (Figure 1B). Further confirm whether CD166tp-G ₁₈ C-FITC is labeled on the surface of CD166 ⁺ HCT15 cells. For analysis of the interaction between CD166tp-G ₁₈ C and CD166 proteins, see Figure 1C. CD166 ⁺ HCT15 and CD166 ⁻ HCT15 cells were treated with CD166tp-G ₁₈ C-FITC (20 μg/mL) for 1 hour. The supernatant was collected and treated with biotinylated CD166 polyclonal antibody (2 μg/mL) or untreated streptavidin-containing agar beads (overnight at 4°C). The fluorescent signal of the immunoprecipitate was analyzed by ELISA. Competitive inhibition assay was pretreated with CD166tp-G ₁₈ C (20 μg/mL). Data are expressed as mean±SD(n

3).*P<0.05 means. The results showed that according to the results of immunoprecipitation analysis, the CD166 antibody was used to measure the results. The results showed that through the interaction with the CD166 protein, CD166tp-G ₁₈ C-FITC could bind to CD16 ⁶⁺ HCT15 cells, but could not bind to CD166- HCT15 cells. And the increase in CD166tp-G ₁₈ C-FITC binding can be inhibited by non-fluorescent CD166tp-G ₁₈ C pretreatment.

Example 3 Preparation of DTPA-CD166tp-G ₁₈ C

In order to synthesize DTPA-conjugated CD166tp-G ₁₈ C (DTPA-CD166tp-G ₁₈ C), CD166tp-G ₁₈ C and maleimide-DTPA (w/w 1:50) were dissolved in sodium carbonate buffer (pH 8.0) for 8 hours. The reaction mixture was then purified by HPLC (Ultimate 3000; Thermo Dionex, Sunnyvale, CA, USA) using a C18 column, linear gradient 10 to 80% acetonitrile/water (0.1% trifluoroacetic acid), 30 min, flow rate 0.3 ml/min. Detection of maleimide-DTPA and CD166tp-G using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (ultraflexIII MS TOFTOF; Bruker Daltonics, Billerica, MA, USA) Molecular weight of ₁₈ C and DTPA-CD166tpG ₁₈ C. Mass spectrometry results were processed with FlexAnalysis ^TM 3.0 software (Bruker Daltonics). According to the analysis results, the molecular weight of maleimide-DTPA is 630.51, the molecular weight of CD166tp-G ₁₈ C is 2372.09, and the molecular weight of DTPA-CD166tpG1 ₁₈ C is 3001.63.

Example 4 Preparation of ¹¹¹ In-DTPA-CD166tp-G ₁₈ C

In the labeling step of radionuclide, 0.1mg DTPA-CD166tp-G ₁₈ C and 370MBq In-111 were reacted in PBS buffer (pH 7.4) for 1 hour at room temperature to prepare ¹¹¹ In-DTPA-CD166tp- _G18C . Next, instant thin-layer chromatography (ITLC) was used to detect the labeling efficiency. According to the measurement results of real-time thin layer chromatography analysis, ^{the 111} In-DTPACD166tp-G ₁₈ C labeling efficiency is greater than 98%.

Example 5 ¹¹¹ In-DTPA-CD166tp-G ₁₈ C stability analysis

Example 18.5MBq ¹¹¹ In-DTPA-CD166tp-G ₁₈ C were cultured in culture dishes (6cm) containing human serum, fetal calf serum or mouse serum, and cultured at 37°C for 144 hours. The yield of ¹¹¹ InDTPA-CD166tp-G ₁₈ C radioactive labeling was detected by ITLC on silica-impregnated glass fiber plates (PALL Company, USA) every 24 hours, using PBS buffer (pH 7.4) as the mobile phase, and the results were expressed as mean±SD (n=5) represents (Fig. 2). The results showed that no matter what kind of serum samples ¹¹¹ InDTPA-CD166tp-G ₁₈ C was used in, the labeling efficiency was greater than 98% after 144 hours, and the stability was good.

Example 6 Therapeutic effect of ¹¹¹ In-DTPA-CD166tp-G ₁₈ C on animals with colorectal cancer

3)顯示，*P<0.05,vs對照組。競爭試驗的結果，請參見第3B圖，數據以mean±SD(n=3)顯示。*P<0.05,vs 100mm³(CD166^-HCT15)；#P<0.05,vs 150mm³(CD166^-HCT15)。由此可以證實，本發明¹¹¹In-DTPA-CD166tp-G₁₈C能夠專一性的聚積在腫瘤處，腫瘤攝取量佳，並且堆積於腫瘤處的時間長，能夠延長作用期間。 BALB/c mice were subcutaneously injected with CD166 ⁺ human colorectal cancer cells (HCT15, 1╳10 ⁶ cells) in the right hind leg and allowed to grow for two weeks. After that, ¹¹¹ In-DTPA and ¹¹¹ In-DTPA-G ₁₈ C were injected intravenously. and ¹¹¹ In-DTPA-CD166tp-G ₁₈ C (740 MBq/kg/mouse). NanoSPE CT/CT image analysis was performed at 2, 4, 24, and 48 hours. In competition experiments, CD166 ⁺ HTC15 xenograft mice were first treated with CD166tp-G ₁₈ C (0, 10 and 50 mg/kg) for 6 hours, and each mouse then received an intravenous injection ^{of 111} In-DTPA-CD166tp-G. ₁₈ C (740MBq/kg/mouse), and nanoSPECT/CT image analysis was performed at 24 and 48 hours, and quantitative analysis was performed using 3D analysis software. The results show that in Figure 3A, compared to the control group (e.g., ¹¹¹ In-DTPA, ¹¹¹ In-DTPA-G ₁₈ C and ¹¹¹ In-DTPA-CD166tp-C), ¹¹¹ In-DTPA-CD166tp-G The amount of ₁₈ C accumulated in tumors increased significantly, and the data are expressed as mean ± SD (n

3) Display, *P<0.05, vs control group. For the results of the competition experiment, see Figure 3B, data are shown as mean±SD (n=3). *P<0.05, vs 100mm ³ (CD166 ^- HCT15); #P<0.05, vs 150mm ³ (CD166 ^- HCT15). It can be confirmed from this that the ¹¹¹ In-DTPA-CD166tp-G ₁₈ C of the present invention can specifically accumulate at the tumor, has good tumor uptake, and accumulates at the tumor for a long time, which can prolong the action period.

Example 7 ¹¹¹ InDTPA-CD166tp-G ₁₈ C colorectal cancer animal biodistribution

BALB/c mice were subcutaneously injected with CD166 ⁺ human colorectal cancer cells (HCT15, 1╳10 ⁶ cells) in the right hind leg, and after tumor formation, ¹¹¹ In-DTPA, ¹¹¹ In-DTPA-G ₁₈ C and ¹¹¹ were injected intravenously. In-DTPA-CD166tp-G ₁₈ C (148MBq/kg/mouse). Animals were sacrificed at 2, 4, 24, and 48 hours after administration to collect organs (brain, heart, lungs, liver, kidney, spleen, stomach, large intestine, small intestine, tumor, muscle, and blood), and the weight of the tissues and organs was measured. , and read the radioactivity on a gamma counter. The radioactive count per gram of tissue (g) is expressed as a bar graph as a percentage (%) of the total radioactive count injected (Injected Dose, ID) as the unit (%ID/g). Data are expressed as mean±SEM (n=3).

The results of the biodistribution analysis are shown in Figures 4 and 5. In Figure 4, compared to the control group ( ¹¹¹ In-DTPA, ¹¹¹ In-DTPA-G ₁₈ C and ¹¹¹ In-DTPA-CD166tp-C), ¹¹¹ In-DTPA-CD166tp-G ₁₈ C in tumor tissue The radionuclide signal is the strongest. Furthermore, tumors in CD166 ⁺ HCT-15 xenograft mice treated with ¹¹¹ In-DTPA, ¹¹¹ In-DTPA-G ₁₈ C, ¹¹¹ InDTPA-CD166tp-C-, or ¹¹¹ In-DTPA-CD166tp-G ₁₈ C were evaluated /muscle ratio (T/M) and tumor/blood ratio (T/B). Compared with the control group ( ¹¹¹ In-DTPA, ¹¹¹ In-DTPA-G ₁₈ C and ¹¹¹ In-DTPA-CD166tp-C), in the ¹¹¹ In-DTPACD166tp-G ₁₈ C treated group, T/M and T/ The B ratio was significantly increased, and these results show that ¹¹¹ In-DTPA-CD166tp-G ₁₈ C has targeting efficacy in CD16 6 ⁺ colorectal cancer tumor tissues.

In summary, the above test results can confirm that the synthetic peptide proposed by the present invention can detect CD166 ⁺ cancer cells in colorectal cancer tumor tissue, and has the potential to become a novel diagnostic peptide and cancer treatment drug.

                        SEQUENCE LISTING
          <![CDATA[<110> Nuclear Energy Research Institute of the Atomic Energy Commission of the Executive Yuan]]>
          <![CDATA[<120> CD166-targeted synthetic peptides, compositions and contrast agents]]>
          <![CDATA[<130> 1090133]]>
          <![CDATA[<160> 11]]>
          <![CDATA[<170> BiSSAP 1.3.6]]>
          <![CDATA[<210> 1]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> Artificial Sequence]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> synthetic;CD166eg]]>
          <![CDATA[<400> 1]]>
          Glu Gly His Cys Asn Asn Gln Ile Cys Ser Asn Gln
          1 5 10
          <![CDATA[<210> 2]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> Artificial Sequence]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> synthetic;CD166et]]>
          <![CDATA[<400> 2]]>
          Glu Thr Glu Thr Gln Gly Thr Val Cys Gly Gly Cys
          1 5 10
          <![CDATA[<210> 3]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> Artificial Sequence]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> synthetic;CD166kc]]>
          <![CDATA[<400> 3]]>
          Lys Cys Asp Asn Gly Thr Val Ala Cys Asn Gln Thr
          1 5 10
          <![CDATA[<210> 4]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> Artificial Sequence]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> synthetic;CD166dn]]>
          <![CDATA[<400> 4]]>
          Asp Asn Lys Cys Ser Asn Thr Ala Gln Thr Asn Gly
          1 5 10
          <![CDATA[<210> 5]]>
          <![CDATA[<211> 11]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> Artificial Sequence]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> synthetic;CD166hq]]>
          <![CDATA[<400> 5]]>
          His Gln His Gly Asn Asn Thr Ile Gly Gly Asn
          1 5 10
          <![CDATA[<210> 6]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> Artificial Sequence]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> synthetic;CD166tp]]>
          <![CDATA[<400> 6]]>
          Asp Ser Glu Gly Asn Ser Asn Leu Cys Ser Gln Ser
          1 5 10
          <![CDATA[<210> 7]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> Artificial Sequence]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> synthetic;CD166kg]]>
          <![CDATA[<400> 7]]>
          Lys Gly Arg Pro Gln Ser Thr Met Pro Asn Ser Gln
          1 5 10
          <![CDATA[<210> 8]]>
          <![CDATA[<211>]]> 12
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> Artificial Sequence]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> synthetic;CD166dne]]>
          <![CDATA[<400> 8]]>
          Asp Asn Glu Ser Ser Thr Asn Ile Thr Gln Thr Ser
          1 5 10
          <![CDATA[<210> 9]]>
          <![CDATA[<211> 19]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> Artificial Sequence]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> synthetic;G18C]]>
          <![CDATA[<400> 9]]>
          Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly
          1 5 10 15
          Gly Gly Cys
          <![CDATA[<210> 10]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> Artificial Sequence]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> synthetic;CD166tp-C]]>
          <![CDATA[<400> 10]]>
          Ser Glu Gly Asn Ser Asn Leu Cys Ser Gln Ser Cys
          1 5 10
          <![CDATA[<210> 11]]>
          <![CDATA[<211> 31]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> Artificial Sequence]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> synthetic;CD166tp-G18C]]>
          <![CDATA[<40]]>0> 11]]&gt;
          <br/><![CDATA[Asp Ser Glu Gly Asn Ser Asn Leu Cys Ser Gln Ser Gly Gly Gly Gly
          1 5 10 15
          Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly Cys
                      20 25 30
          
      

Claims (8)

A synthetic peptide that binds to CD166, comprising: a binding peptide having an amino acid sequence of sequence number 6 (DSEGNSNLCSQS); and an additional peptide connected to the binding peptide having sequence number 9 ( Amino acid sequence of G ₁₈ C). A composition that binds CD166, comprising: the synthetic peptide as described in claim 1; and a fluorescent label labeled on the synthetic peptide. A composition that binds to CD166, comprising: the synthetic peptide as described in claim 1; a metal chelating agent coupled to the synthetic peptide; and a radioactive nuclide marked on the metal chelating agent. The composition of claim 3, wherein the metal chelating agent is selected from the group consisting of: 1,4,7,10-tetraazacyclododecane-1,4,7,10- Tetraacetic acid (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, DOTA), 1,4,7-triazacyclononane-1,4,7-triacetic acid (1 ,4,7-triazacyclononane-1,4,7-triacetic acid, NOTA), 1,4,7-triazacyclononane-1,4-diacetic acid (1,4,7-triazacyclononane-1,4 -diacetic acid (NODA) and diethylenetriaminepenta-acetic acid (DTPA). The composition of claim 3, wherein the radioactive nuclide is selected from the group consisting of: Ga-66, Ga-67, Ga-68, Zr-89, Lu-177, In-111, I -123. The composition of claim 5, wherein the radioactive nuclide is In-111. The composition of claim 5, wherein the metal chelating agent is DTPA. A contrast agent, comprising: the composition shown in claim 4; and a contrast excipient.

Images