Journal of Radioanalytical and Nuclear Chemistry

, Volume 318, Issue 3, pp 2059–2066 | Cite as

177Lu-DOTA-HYNIC-Lys(Nal)-Urea-Glu: synthesis and assessment of the ability to target the prostate specific membrane antigen

  • Tania Hernández-Jiménez
  • Guillermina Ferro-FloresEmail author
  • Blanca Ocampo-García
  • Enrique Morales-Avila
  • Alondra Escudero-Castellanos
  • Erika Azorín-Vega
  • Clara Santos-Cuevas
  • Myrna Luna-Gutiérrez
  • Nallely Jiménez-Mancilla
  • Luis Alberto Medina
  • Flor de Maria Ramirez
  • Martha Pedraza-López


SPECT/CT images have proved the capability of 99mTc-EDDA/HYNIC-Lys(β-naphthylalanine)-NH-CO-NH-Glu to detect prostate cancer tumors in patients. Considering that theranostics combines the potential of therapeutic and diagnostic radionuclides in the same molecular probe, this research aimed to prepare 177Lu-DOTA-HYNIC-Lys(β-naphthylalanine)-NH-CO-NH-Glu (177Lu-iPSMA) and evaluate the in vitro and in vivo radiotracer ability to target the PSMA protein overexpressed in prostate cancer cells (LNCaP). 177Lu-iPSMA, obtained with radiochemical purities of 99%, showed specific in vitro and in vivo recognition for PSMA in prostate cancer cells and high LNCaP-tumor uptake (11 ± 2% ID/g at 24 h). The results obtained warrant further studies to evaluate the therapeutic efficacy of 177Lu-iPSMA.


DOTA-HYNIC-PSMA inhibitor 177Lu-iPSMA Prostate cancer Theranostic pair 



This research received financial support from the Mexican National Council of Science and Technology (CONACyT-Mexico, Grant 242443). This work was performed as part of the activities of the ‘‘Laboratorio Nacional de Investigación y Desarrollo de Radiofármacos, CONACyT’’.

Compliance with ethical standards

Conflict of interest

The authors declare no potential conflicts of interest with regard to the research, authorship, and/or publication of this article.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This research was approved by the CICUAL-ININ ethics committee (Internal committee of care and use of laboratory animals of the National Institute of Nuclear Research, Approval No. 01/02/2018).


  1. 1.
    Ferlay J, Soerjomataram I, Dikshit R et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359–E386CrossRefGoogle Scholar
  2. 2.
    Santoni M, Scarpelli M, Mazzucchelli R et al (2013) Targeting prostate-specific membrane antigen for personalized therapies in prostate cancer: morphologic and molecular backgrounds and future promises. J Biol Regul Homeost Agents 28:555–563Google Scholar
  3. 3.
    Rajasekaran AK, Anilkumar G, Christiansen JJ (2005) Is prostate-specific membrane antigen a multifunctional protein? Am J Physiol Cell Physiol 288:C975–C981CrossRefGoogle Scholar
  4. 4.
    Benešová M, Schäfer M, Bauder-Wüst U et al (2015) Preclinical evaluation of a tailor-made DOTA-conjugated PSMA inhibitor with optimized linker moiety for imaging and endoradiotherapy of prostate cancer. J Nucl Med 56:914–920CrossRefGoogle Scholar
  5. 5.
    Rahbar K, Schmidt M, Heinzel A et al (2016) Response and tolerability of a single dose of 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer: a multicenter retrospective analysis. J Nucl Med 57:1334–1338CrossRefGoogle Scholar
  6. 6.
    Rahbar K, Ahmadzadehfar H, Kratochwil C et al (2017) German multicenter study investigating 177Lu-PSMA-617 radioligand therapy in advanced prostate cancer patients. J Nucl Med 58:85–90CrossRefGoogle Scholar
  7. 7.
    Baum RP, Kulkarni HR, Schuchardt C et al (2016) 177Lu-labeled prostate-specific membrane antigen radioligand therapy of metastatic castration-resistant prostate cancer: safety and efficacy. J Nucl Med 57:1006–1013CrossRefGoogle Scholar
  8. 8.
    Eder M, Neels O, Müller M et al (2014) Novel preclinical and radiopharmaceutical aspects of [68Ga] Ga-PSMA-HBED-CC: a new PET tracer for imaging of prostate cancer. Pharmaceuticals 7:779–796CrossRefGoogle Scholar
  9. 9.
    Weineisen M, Schottelius M, Simecek J et al (2015) 68Ga-and 177Lu-labeled PSMA I&T: optimization of a PSMA-targeted theranostic concept and first proof-of-concept human studies. J Nucl Med 56:1169–1176CrossRefGoogle Scholar
  10. 10.
    Afshar-Oromieh A, Haberkorn U, Schlemmer H et al (2014) Comparison of PET/CT and PET/MRI hybrid systems using a 68Ga-labelled PSMA ligand for the diagnosis of recurrent prostate cancer: initial experience. Eur J Nucl Med Mol Imaging 41:887–897CrossRefGoogle Scholar
  11. 11.
    Ferro-Flores G, Luna-Gutiérrez M, Ocampo-Garcia B et al (2017) Clinical translation of a PSMA inhibitor for 99mTc-based SPECT. Nucl Med Biol 48:36–44CrossRefGoogle Scholar
  12. 12.
    Santos-Cuevas C, Davanzo J, Ferro-Flores G et al (2017) 99mTc-labeled PSMA inhibitor: Biokinetics and radiation dosimetry in healthy subjects and imaging of prostate cancer tumors in patients. Nucl Med Biol 52:1–6CrossRefGoogle Scholar
  13. 13.
    Ferro-Flores G, Ocampo-Garcia B, Santos-Cuevas C et al (2017) 99mTc-EDDA/HYNIC-iPSMA as a radiopharmaceutical for detecting the overexpression of prostate-specific membrane antigen. Patent Cooperation Treaty Application. Patent No. WO2017222362Google Scholar
  14. 14.
    Luna-Gutierrez M, Jimenez-Hernandez T, Serrano-Espinoza L et al (2017) Freeze-dried multi-dose kits for the fast preparation of 177Lu-Tyr3-octreotide and 177Lu-PSMA(inhibitor) under GMP conditions. J Radioanal Nucl Chem 314:2181–2188CrossRefGoogle Scholar
  15. 15.
    Choy CJ, Ling X, Geruntho JJ et al (2017) 177Lu-Labeled phosphoramidate-based PSMA inhibitors: the effect of an albumin binder on biodistribution and therapeutic efficacy in prostate tumor-bearing mice. Theranostics 7:1928–1939CrossRefGoogle Scholar
  16. 16.
    Eder M, Schäfer M, Bauder-Wüst U et al (2014) Preclinical evaluation of a bispecific low-molecular heterodimer targeting both PSMA and GRPR for improved PET imaging and therapy of prostate cancer. Prostate 74:659–668CrossRefGoogle Scholar
  17. 17.
    Wüstemann T, Bauder-Wüst U, Schäfer M et al (2016) Design of Internalizing PSMA-specific Glu-ureido-based radiotherapeuticals. Theranostics 6:1085–1095CrossRefGoogle Scholar
  18. 18.
    Bacich DJ, Pinto JT, Tong WP et al (2001) Cloning, expression, genomic localization, and enzymatic activities of the mouse homolog of prostate-specific membrane antigen/NAALADase/folate hydrolase. Mamm Genome 12:117–123CrossRefGoogle Scholar
  19. 19.
    Emmett L, Willowson K, Violet J et al (2017) Lutetium177 PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy. J Med Radiat Sci 64:52–60CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2018

Authors and Affiliations

  • Tania Hernández-Jiménez
    • 1
    • 2
  • Guillermina Ferro-Flores
    • 1
    Email author
  • Blanca Ocampo-García
    • 1
  • Enrique Morales-Avila
    • 2
  • Alondra Escudero-Castellanos
    • 1
  • Erika Azorín-Vega
    • 1
  • Clara Santos-Cuevas
    • 1
  • Myrna Luna-Gutiérrez
    • 1
  • Nallely Jiménez-Mancilla
    • 3
  • Luis Alberto Medina
    • 4
  • Flor de Maria Ramirez
    • 5
  • Martha Pedraza-López
    • 6
  1. 1.Departamento de Materiales RadiactivosInstituto Nacional de Investigaciones NuclearesOcoyoacacMexico
  2. 2.Facultad de QuímicaUniversidad Autónoma del Estado de MéxicoTolucaMexico
  3. 3.CONACyT, Instituto Nacional de Investigaciones NuclearesOcoyoacacMexico
  4. 4.Unidad de Investigación Biomédica en Cáncer INCan/UNAMInstituto Nacional de CancerologíaTlalpanMexico
  5. 5.Departamento de QuímicaInstituto Nacional de Investigaciones NuclearesOcoyoacacMexico
  6. 6.Departamento de Medicina NuclearInstituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránTlalpanMexico

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