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18F-Labelled PSMA-1007 shows similarity in structure, biodistribution and tumour uptake to the theragnostic compound PSMA-617

  • Frederik L. Giesel
  • Jens Cardinale
  • Martin Schäfer
  • Oliver Neels
  • Martina Benešová
  • Walter Mier
  • Uwe Haberkorn
  • Klaus Kopka
  • Clemens Kratochwil
Open Access
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Keywords

Prostate Cancer Maximum Intensity Projection Tumour Uptake Carboxylic Acid Group Radionuclide Therapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

The biochemical and radiological responses to radionuclide therapy with 177Lu-PSMA-617 targeting prostate-specific membrane antigen (PSMA) make it a promising approach to the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) [1]. However, PSMA-617 has been reported to have slower tumour accumulation and clearance kinetics than PSMA-11, and the latter is still therefore the preferred diagnostic agent when labelled with generator-produced 68Ga which has a short half-life (68 min) [2]. A PSMA-targeting 18F-labelled PET tracer could be produced with higher activity in a cyclotron and the half-life (110 min) would allow both late imaging beyond 1 h after injection and shipping to satellite institutions. However, the structure of the currently most-used 18F-labelled PSMA tracer, 18F-DCFPyl, is different from that of PSMA-617, and like PSMA-11 it might be a suboptimal surrogate for stratifying patients according to their suitability for therapy with 177Lu-PSMA-617 [3].

Based on the scaffold of PSMA-617, the novel compound 18F-PSMA-1007 was developed. As shown in the image (a, d), PSMA-1007 shares the Glu-urea-Lys motif targeting the catalytic domain of PSMA and the naphthalene-based linker region considered to cotarget the hydrophobic accessory pocket [4], while in the radiolabel-bearing moiety glutamic acids were added to mimic the carboxylic acid groups of the DOTA chelator to retain the polar charge influencing clearance kinetics.

The image also shows a patient with mCRPC who was staged using 18F-PSMA-1007 (b PET 1 h after injection, maximum intensity projection) and treatment with 177Lu-PSMA-617 (c planar scan 24 h after injection, geometric mean). In analogy to the chemical structure, the uptake in tumour and normal organs is very similar with the two compounds.

Thus, 18F-PSMA-1007 and 177Lu-PSMA-617 seem to be a perfect theragnostic tandem. Due to the preferred physical characteristics of 18F for PET imaging and the possibility for large-scale production in a cyclotron, 18F-PSMA-1007 is also a promising alternative to 68Ga-PSMA-11 for diagnostic purposes. However, non-inferior diagnostic accuracy has still to be proven in a larger cohort.

Notes

Compliance with ethical standards

Ethical approval

As this is a retrospective case report of a patient in regular clinical care but not a clinical trial, ethical approval was not needed.

Informed consent

Written informed consent for imaging with an experimental tracer and publication of the individual patient history was obtained.

References

  1. 1.
    Kratochwil C, Giesel FL, Stefanova M, Benešová M, Bronzel M, Afshar-Oromieh A, et al. PSMA-targeted radionuclide therapy of metastatic castration-resistant prostate cancer with Lu-177 labeled PSMA-617. J Nucl Med. 2016. doi: 10.2967/jnumed.115.171397.Google Scholar
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    Afshar-Oromieh A, Hetzheim H, Kratochwil C, Benesova M, Eder M, Neels OC, et al. The theranostic PSMA ligand PSMA-617 in the diagnosis of prostate cancer by PET/CT: biodistribution in humans, radiation dosimetry, and first evaluation of tumor lesions. J Nucl Med. 2015;56(11):1697–705. doi: 10.2967/jnumed.115.161299.CrossRefPubMedGoogle Scholar
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    Szabo Z, Mena E, Rowe SP, Plyku D, Nidal R, Eisenberger MA, et al. Initial evaluation of [(18)F]DCFPyL for prostate-specific membrane antigen (PSMA)-targeted PET imaging of prostate cancer. Mol Imaging Biol. 2015;17(4):565–74. doi: 10.1007/s11307-015-0850-8.CrossRefPubMedPubMedCentralGoogle Scholar
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Copyright information

© The Author(s) 2016

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  1. 1.Department for Nuclear MedicineUniversity Hospital HeidelbergHeidelbergGermany
  2. 2.Division of Radiopharmaceutical ChemistryGerman Cancer Research Center (DKFZ)HeidelbergGermany

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