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PET radiotracers for whole-body in vivo molecular imaging of prostatic neuroendocrine malignancies

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Abstract

Prostatic neuroendocrine malignancies represent a spectrum of diseases. Treatment-induced neuroendocrine differentiation (tiNED) in hormonally treated adenocarcinoma has been the subject of a large amount of recent research. However, the identification of neuroendocrine features in treatment-naïve prostatic tumor raises a differential diagnosis between prostatic adenocarcinoma with de novo neuroendocrine differentiation (dNED) versus one of the primary prostatic neuroendocrine tumors (P-NETs) and carcinomas (P-NECs). While [18F]FDG is being used as the main PET radiotracer in oncologic imaging and reflects cellular glucose metabolism, other molecules labeled with positron-emitting isotopes, mainly somatostatin-analogues labeled with 68Ga and prostate-specific membrane antigen (PSMA)-ligands labeled with either 18F or 68Ga, are now routinely used in departments of nuclear medicine and molecular imaging, and may be advantageous in imaging prostatic neuroendocrine malignancies. Still, the selection of the preferred PET radiotracer in such cases might be challenging. In the current review, we summarize and discuss published data on these different entities from clinical, biological, and molecular imaging standpoints. Specifically, we review the roles that [18F]FDG, radiolabeled somatostatin-analogues, and radiolabeled PSMA-ligands play in these entities in order to provide the reader with practical recommendations regarding the preferred PET radiotracers for imaging each entity. In cases of tiNED, we conclude that PSMA expression may be low and that [18F]FDG or radiolabeled somatostatin-analogues should be preferred for imaging. In cases of prostatic adenocarcinoma with dNED, we present data that support the superiority of radiolabeled PSMA-ligands. In cases of primary neuroendocrine malignancies, the use of [18F]FDG for imaging high-grade P-NECs and radiolabeled somatostatin-analogues for imaging well-differentiated P-NETs is recommended.

Key Points

• The preferred PET radiotracer for imaging prostatic neuroendocrine malignancies depends on the specific clinical scenario and pathologic data.

• When neuroendocrine features result from hormonal therapy for prostate cancer, PET-CT should be performed with [ 18 F]FDG or radiolabeled somatostatin-analogue rather than with radiolabeled PSMA-ligand.

• When neuroendocrine features are evident in newly diagnosed prostate cancer, differentiating adenocarcinoma from primary neuroendocrine malignancy is challenging but crucial for selection of PET radiotracer and for clinical management.

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Abbreviations

[18F]FDG:

18F-Fluorodeoxyglucose

ADT:

Androgen-deprivation therapy

CRPC:

Castration-resistant prostate cancer

dNED:

De novo neuroendocrine differentiation

DOTATATE:

Dodecane tetraacetic acid-octreotate

H&E:

Hematoxylin and eosin

MIP:

Maximal intensity projection

PET-CT:

Positron emission tomography–computed tomography

P-NEC:

Primary prostatic neuroendocrine carcinoma

P-NET:

Primary prostatic neuroendocrine tumor

PSA:

Prostate-specific antigen

PSMA:

Prostate-specific membrane antigen

SSTR:

Somatostatin-receptor

tiNED:

Treatment-induced neuroendocrine differentiation

TURBT:

Transurethral resection of bladder tumor

TURP:

Transurethral resection of prostate

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The authors state that this work has not received any funding.

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, Tel-Aviv Sourasky Medical Center, 6 Weizmann St, 6423906, Tel Aviv, Israel

    Dan Cohen, Shir Hazut Krauthammer, Mikhail Kesler & Einat Even-Sapir

  2. Institute of Pathology, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel

    Ibrahim Fahoum

  3. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Einat Even-Sapir

Authors
  1. Dan Cohen
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  2. Shir Hazut Krauthammer
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  3. Ibrahim Fahoum
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  4. Mikhail Kesler
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  5. Einat Even-Sapir
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Correspondence to Dan Cohen.

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The scientific guarantor of this publication is Einat Even-Sapir.

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The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

No complex statistical methods were necessary for this paper.

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Written informed consent was waived by the Institutional Review Board.

Ethical approval

Data presented in the figures included in this paper were available as part of retrospective study protocols approved by the local institutional ethics committee, which waived written informed consent (Reference ID 0487/1102–20-TLV).

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Cohen, D., Hazut Krauthammer, S., Fahoum, I. et al. PET radiotracers for whole-body in vivo molecular imaging of prostatic neuroendocrine malignancies. Eur Radiol 33, 6502–6512 (2023). https://doi.org/10.1007/s00330-023-09619-8

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  • DOI: https://doi.org/10.1007/s00330-023-09619-8

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