In vivo imaging of Aminopeptidase N (CD13) receptors in experimental renal tumors using the novel radiotracer68Ga-NOTA-c(NGR)

Gábor Máté, István Kertész, Kata Nóra Enyedi, G. Mező, János Angyal, Nikolett Vasas, Adrienn Kis, Éva Szabó, M. Emri, T. Bíró, L. Galuska, György Trencsényi

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Purpose: Aminopeptidase N (APN/CD13) plays an important role in tumor neoangiogenic process and the development of metastases. Furthermore, it may serve as a potential target for cancer diagnosis and therapy. Previous studies have already shown that asparagine-glycine-arginine (NGR) peptides specifically bind to APN/CD13. The aim of the study was to synthesize and investigate the APN/CD13 specificity of a novel 68Ga-labeled NOTA-c(NGR) molecule in vivo using miniPET. Methods: c[KNGRE]-NH2 peptide was conjugated with p-SCN-Bn-NOTA and was labeled with Ga-68 (68Ga-NOTA-c(NGR)). Orthotopic and heterotopic transplanted mesoblastic nephroma (NeDe) bearing Fischer-344 rats were prepared, on which biodistribution studies and miniPET scans were performed for both 68Ga-NOTA-c(NGR) and ανβ3 integrin selective 68Ga-NODAGA-[c(RGD)]2 tracers. APN/CD13 receptor expression of NeDe tumors and metastases was analyzed by western blot. Results: 68Ga-NOTA-c(NGR) was produced with high specific activity (5.13-5.92 GBq/μmol) and with excellent radiochemical purity (95%68Ga-NOTA-c(NGR) was significantly (p ≤ 0.05) lower in abdominal organs in comparison with 68Ga-NODAGA-[c(RGD)]2. Both radiotracers were mainly excreted from the kidney. In NeDe tumor bearing rats higher 68Ga-NOTA-c(NGR) accumulation was found in the tumors than that of the 68Ga-NOD-AGA-[c(RGD)]2. Using orthotopic transplantation, metastases were developed which showed specific 68Ga-NOTA-c(NGR) uptake. Western blot analysis confirmed the presence of APN/CD13 expression in NeDe tumors and metastases. Conclusion: Our novel radiotracer 68Ga-NOTA-c(NGR) showed specific binding to the APN/CD13 expressed ortho- and heterotopic transplanted NeDe tumors. Therefore, 68Ga-NOTA-c(NGR) is a suitable tracer for the detection of APN/CD13 positive tumors and metastases in vivo.

Original languageEnglish
Pages (from-to)61-71
Number of pages11
JournalEuropean Journal of Pharmaceutical Sciences
Volume69
DOIs
Publication statusPublished - Mar 10 2015

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CD13 Antigens
Kidney
Neoplasms
Neoplasm Metastasis
NGR peptide
Mesoblastic Nephroma
Western Blotting
1,4,7-triazacyclononane-N,N',N''-triacetic acid
68Ga-NOTA-c(NGR)
Asparagine
Inbred F344 Rats
Integrins
Glycine
Arginine
Transplantation
Peptides

Keywords

  • Ga-NODAGA-[c(RGD)]
  • Ga-NOTA-c(NGR)
  • Aminopeptidase N (CD13) expression
  • Positron emission tomography
  • Renal tumors
  • Tumor angiogenesis

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Medicine(all)

Cite this

In vivo imaging of Aminopeptidase N (CD13) receptors in experimental renal tumors using the novel radiotracer68Ga-NOTA-c(NGR). / Máté, Gábor; Kertész, István; Enyedi, Kata Nóra; Mező, G.; Angyal, János; Vasas, Nikolett; Kis, Adrienn; Szabó, Éva; Emri, M.; Bíró, T.; Galuska, L.; Trencsényi, György.

In: European Journal of Pharmaceutical Sciences, Vol. 69, 10.03.2015, p. 61-71.

Research output: Contribution to journalArticle

Máté, Gábor ; Kertész, István ; Enyedi, Kata Nóra ; Mező, G. ; Angyal, János ; Vasas, Nikolett ; Kis, Adrienn ; Szabó, Éva ; Emri, M. ; Bíró, T. ; Galuska, L. ; Trencsényi, György. / In vivo imaging of Aminopeptidase N (CD13) receptors in experimental renal tumors using the novel radiotracer68Ga-NOTA-c(NGR). In: European Journal of Pharmaceutical Sciences. 2015 ; Vol. 69. pp. 61-71.
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abstract = "Purpose: Aminopeptidase N (APN/CD13) plays an important role in tumor neoangiogenic process and the development of metastases. Furthermore, it may serve as a potential target for cancer diagnosis and therapy. Previous studies have already shown that asparagine-glycine-arginine (NGR) peptides specifically bind to APN/CD13. The aim of the study was to synthesize and investigate the APN/CD13 specificity of a novel 68Ga-labeled NOTA-c(NGR) molecule in vivo using miniPET. Methods: c[KNGRE]-NH2 peptide was conjugated with p-SCN-Bn-NOTA and was labeled with Ga-68 (68Ga-NOTA-c(NGR)). Orthotopic and heterotopic transplanted mesoblastic nephroma (NeDe) bearing Fischer-344 rats were prepared, on which biodistribution studies and miniPET scans were performed for both 68Ga-NOTA-c(NGR) and ανβ3 integrin selective 68Ga-NODAGA-[c(RGD)]2 tracers. APN/CD13 receptor expression of NeDe tumors and metastases was analyzed by western blot. Results: 68Ga-NOTA-c(NGR) was produced with high specific activity (5.13-5.92 GBq/μmol) and with excellent radiochemical purity (95{\%}68Ga-NOTA-c(NGR) was significantly (p ≤ 0.05) lower in abdominal organs in comparison with 68Ga-NODAGA-[c(RGD)]2. Both radiotracers were mainly excreted from the kidney. In NeDe tumor bearing rats higher 68Ga-NOTA-c(NGR) accumulation was found in the tumors than that of the 68Ga-NOD-AGA-[c(RGD)]2. Using orthotopic transplantation, metastases were developed which showed specific 68Ga-NOTA-c(NGR) uptake. Western blot analysis confirmed the presence of APN/CD13 expression in NeDe tumors and metastases. Conclusion: Our novel radiotracer 68Ga-NOTA-c(NGR) showed specific binding to the APN/CD13 expressed ortho- and heterotopic transplanted NeDe tumors. Therefore, 68Ga-NOTA-c(NGR) is a suitable tracer for the detection of APN/CD13 positive tumors and metastases in vivo.",
keywords = "Ga-NODAGA-[c(RGD)], Ga-NOTA-c(NGR), Aminopeptidase N (CD13) expression, Positron emission tomography, Renal tumors, Tumor angiogenesis",
author = "G{\'a}bor M{\'a}t{\'e} and Istv{\'a}n Kert{\'e}sz and Enyedi, {Kata N{\'o}ra} and G. Mező and J{\'a}nos Angyal and Nikolett Vasas and Adrienn Kis and {\'E}va Szab{\'o} and M. Emri and T. B{\'i}r{\'o} and L. Galuska and Gy{\"o}rgy Trencs{\'e}nyi",
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month = "3",
day = "10",
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TY - JOUR

T1 - In vivo imaging of Aminopeptidase N (CD13) receptors in experimental renal tumors using the novel radiotracer68Ga-NOTA-c(NGR)

AU - Máté, Gábor

AU - Kertész, István

AU - Enyedi, Kata Nóra

AU - Mező, G.

AU - Angyal, János

AU - Vasas, Nikolett

AU - Kis, Adrienn

AU - Szabó, Éva

AU - Emri, M.

AU - Bíró, T.

AU - Galuska, L.

AU - Trencsényi, György

PY - 2015/3/10

Y1 - 2015/3/10

N2 - Purpose: Aminopeptidase N (APN/CD13) plays an important role in tumor neoangiogenic process and the development of metastases. Furthermore, it may serve as a potential target for cancer diagnosis and therapy. Previous studies have already shown that asparagine-glycine-arginine (NGR) peptides specifically bind to APN/CD13. The aim of the study was to synthesize and investigate the APN/CD13 specificity of a novel 68Ga-labeled NOTA-c(NGR) molecule in vivo using miniPET. Methods: c[KNGRE]-NH2 peptide was conjugated with p-SCN-Bn-NOTA and was labeled with Ga-68 (68Ga-NOTA-c(NGR)). Orthotopic and heterotopic transplanted mesoblastic nephroma (NeDe) bearing Fischer-344 rats were prepared, on which biodistribution studies and miniPET scans were performed for both 68Ga-NOTA-c(NGR) and ανβ3 integrin selective 68Ga-NODAGA-[c(RGD)]2 tracers. APN/CD13 receptor expression of NeDe tumors and metastases was analyzed by western blot. Results: 68Ga-NOTA-c(NGR) was produced with high specific activity (5.13-5.92 GBq/μmol) and with excellent radiochemical purity (95%68Ga-NOTA-c(NGR) was significantly (p ≤ 0.05) lower in abdominal organs in comparison with 68Ga-NODAGA-[c(RGD)]2. Both radiotracers were mainly excreted from the kidney. In NeDe tumor bearing rats higher 68Ga-NOTA-c(NGR) accumulation was found in the tumors than that of the 68Ga-NOD-AGA-[c(RGD)]2. Using orthotopic transplantation, metastases were developed which showed specific 68Ga-NOTA-c(NGR) uptake. Western blot analysis confirmed the presence of APN/CD13 expression in NeDe tumors and metastases. Conclusion: Our novel radiotracer 68Ga-NOTA-c(NGR) showed specific binding to the APN/CD13 expressed ortho- and heterotopic transplanted NeDe tumors. Therefore, 68Ga-NOTA-c(NGR) is a suitable tracer for the detection of APN/CD13 positive tumors and metastases in vivo.

AB - Purpose: Aminopeptidase N (APN/CD13) plays an important role in tumor neoangiogenic process and the development of metastases. Furthermore, it may serve as a potential target for cancer diagnosis and therapy. Previous studies have already shown that asparagine-glycine-arginine (NGR) peptides specifically bind to APN/CD13. The aim of the study was to synthesize and investigate the APN/CD13 specificity of a novel 68Ga-labeled NOTA-c(NGR) molecule in vivo using miniPET. Methods: c[KNGRE]-NH2 peptide was conjugated with p-SCN-Bn-NOTA and was labeled with Ga-68 (68Ga-NOTA-c(NGR)). Orthotopic and heterotopic transplanted mesoblastic nephroma (NeDe) bearing Fischer-344 rats were prepared, on which biodistribution studies and miniPET scans were performed for both 68Ga-NOTA-c(NGR) and ανβ3 integrin selective 68Ga-NODAGA-[c(RGD)]2 tracers. APN/CD13 receptor expression of NeDe tumors and metastases was analyzed by western blot. Results: 68Ga-NOTA-c(NGR) was produced with high specific activity (5.13-5.92 GBq/μmol) and with excellent radiochemical purity (95%68Ga-NOTA-c(NGR) was significantly (p ≤ 0.05) lower in abdominal organs in comparison with 68Ga-NODAGA-[c(RGD)]2. Both radiotracers were mainly excreted from the kidney. In NeDe tumor bearing rats higher 68Ga-NOTA-c(NGR) accumulation was found in the tumors than that of the 68Ga-NOD-AGA-[c(RGD)]2. Using orthotopic transplantation, metastases were developed which showed specific 68Ga-NOTA-c(NGR) uptake. Western blot analysis confirmed the presence of APN/CD13 expression in NeDe tumors and metastases. Conclusion: Our novel radiotracer 68Ga-NOTA-c(NGR) showed specific binding to the APN/CD13 expressed ortho- and heterotopic transplanted NeDe tumors. Therefore, 68Ga-NOTA-c(NGR) is a suitable tracer for the detection of APN/CD13 positive tumors and metastases in vivo.

KW - Ga-NODAGA-[c(RGD)]

KW - Ga-NOTA-c(NGR)

KW - Aminopeptidase N (CD13) expression

KW - Positron emission tomography

KW - Renal tumors

KW - Tumor angiogenesis

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JO - European Journal of Pharmaceutical Sciences

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