PSMA expression and PSMA PET/CT imaging in metastatic soft tissue sarcoma patients, results of a prospective study

F. Kleiburg; T. van der Hulle; H. Gelderblom; M. Slingerland; F. M. Speetjens; L. J.A.C. Hawinkels; P. Dibbets-Schneider; F. H.P. van Velden; M. Pool; S. W. Lam; J. V.M.G. Bovée; L. Heijmen; L. F. de Geus-Oei

doi:10.1007/s00259-025-07224-z

PSMA expression and PSMA PET/CT imaging in metastatic soft tissue sarcoma patients, results of a prospective study

F. Kleiburg^*
, T. van der Hulle
, H. Gelderblom
, M. Slingerland
, F. M. Speetjens
, L. J.A.C. Hawinkels
, P. Dibbets-Schneider
, F. H.P. van Velden
, M. Pool
, S. W. Lam
, J. V.M.G. Bovée
, L. Heijmen
, L. F. de Geus-Oei

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Purpose: Prostate-specific membrane antigen (PSMA) expression has been observed in a subset of soft tissue sarcomas, mainly in the neovascular endothelial cells. This feasibility study aimed to evaluate PSMA expression and PSMA PET/CT imaging in metastatic soft tissue sarcoma, providing important insights for potential future exploration of PSMA-targeted radioligand therapy. Methods: This prospective single-center study included adult patients with metastatic soft tissue sarcoma, with measurable disease (lesion diameter > 1 cm), available biopsy/resection material, ECOG/WHO performance status of 0–2 and either no prior systemic treatment, progressive disease during/after treatment, or stable disease/partial response with the last dose > 8 weeks prior. Immunohistochemical PSMA staining was performed on previously obtained biopsy or resection material. In case of high PSMA expression, a [¹⁸F]-JK-PSMA-7 PET/CT scan evaluated tracer uptake, with adequate uptake defined as SUV_max > 8. Results: Of 25 included patients, 11 (44%) had high PSMA expression: 4/11 leiomyosarcomas, 3/4 dedifferentiated liposarcomas, 2/5 undifferentiated pleomorphic sarcomas, 1/2 myxofibrosarcomas and 1/1 malignant peripheral nerve sheath tumour. Five of 11 patients agreed to a [¹⁸F]-JK-PSMA-7 PET/CT, of which 3 had lesions that showed adequate tracer uptake (SUV_max 10.7–16.7). However, uptake across all metastatic lesions was highly heterogeneous (median SUV_max = 3.8; range 0.5–16.7), indicating that these patients are unlikely to benefit sufficiently from PSMA-targeted therapy. The study was therefore terminated prematurely. Conclusion: PSMA expression and PSMA tracer uptake in metastatic soft tissue sarcoma were highly heterogeneous. A deeper understanding of PSMA biology and improved patient selection criteria are essential for future application of PSMA-targeted radioligand therapy in this disease. Trial registration: : clinicaltrials.gov, NCT05522257. Registered 31-08-2022.

Original language	English
Pages (from-to)	3690-3699
Number of pages	10
Journal	European journal of nuclear medicine and molecular imaging
Volume	52
Issue number	10
Early online date	27 Mar 2025
DOIs	https://doi.org/10.1007/s00259-025-07224-z
Publication status	Published - Aug 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

UT-Hybrid-D
Prostate-specific membrane antigen
PSMA
PSMA PET/CT
Soft tissue sarcoma
Theranostics
Molecular imaging

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Kleiburg, F., van der Hulle, T., Gelderblom, H., Slingerland, M., Speetjens, F. M., Hawinkels, L. J. A. C., Dibbets-Schneider, P., van Velden, F. H. P., Pool, M., Lam, S. W., Bovée, J. V. M. G., Heijmen, L., & de Geus-Oei, L. F. (2025). PSMA expression and PSMA PET/CT imaging in metastatic soft tissue sarcoma patients, results of a prospective study. European journal of nuclear medicine and molecular imaging, 52(10), 3690-3699. https://doi.org/10.1007/s00259-025-07224-z

@article{ba7fca1fd7d741d6ad2b695b39985e47,

title = "PSMA expression and PSMA PET/CT imaging in metastatic soft tissue sarcoma patients, results of a prospective study",

abstract = "Purpose: Prostate-specific membrane antigen (PSMA) expression has been observed in a subset of soft tissue sarcomas, mainly in the neovascular endothelial cells. This feasibility study aimed to evaluate PSMA expression and PSMA PET/CT imaging in metastatic soft tissue sarcoma, providing important insights for potential future exploration of PSMA-targeted radioligand therapy. Methods: This prospective single-center study included adult patients with metastatic soft tissue sarcoma, with measurable disease (lesion diameter > 1 cm), available biopsy/resection material, ECOG/WHO performance status of 0{\textendash}2 and either no prior systemic treatment, progressive disease during/after treatment, or stable disease/partial response with the last dose > 8 weeks prior. Immunohistochemical PSMA staining was performed on previously obtained biopsy or resection material. In case of high PSMA expression, a [18F]-JK-PSMA-7 PET/CT scan evaluated tracer uptake, with adequate uptake defined as SUVmax > 8. Results: Of 25 included patients, 11 (44\%) had high PSMA expression: 4/11 leiomyosarcomas, 3/4 dedifferentiated liposarcomas, 2/5 undifferentiated pleomorphic sarcomas, 1/2 myxofibrosarcomas and 1/1 malignant peripheral nerve sheath tumour. Five of 11 patients agreed to a [18F]-JK-PSMA-7 PET/CT, of which 3 had lesions that showed adequate tracer uptake (SUVmax 10.7{\textendash}16.7). However, uptake across all metastatic lesions was highly heterogeneous (median SUVmax = 3.8; range 0.5{\textendash}16.7), indicating that these patients are unlikely to benefit sufficiently from PSMA-targeted therapy. The study was therefore terminated prematurely. Conclusion: PSMA expression and PSMA tracer uptake in metastatic soft tissue sarcoma were highly heterogeneous. A deeper understanding of PSMA biology and improved patient selection criteria are essential for future application of PSMA-targeted radioligand therapy in this disease. Trial registration: : clinicaltrials.gov, NCT05522257. Registered 31-08-2022.",

keywords = "UT-Hybrid-D, Prostate-specific membrane antigen, PSMA, PSMA PET/CT, Soft tissue sarcoma, Theranostics, Molecular imaging",

author = "F. Kleiburg and \{van der Hulle\}, T. and H. Gelderblom and M. Slingerland and Speetjens, \{F. M.\} and Hawinkels, \{L. J.A.C.\} and P. Dibbets-Schneider and \{van Velden\}, \{F. H.P.\} and M. Pool and Lam, \{S. W.\} and Bov{\'e}e, \{J. V.M.G.\} and L. Heijmen and \{de Geus-Oei\}, \{L. F.\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = aug,

doi = "10.1007/s00259-025-07224-z",

language = "English",

volume = "52",

pages = "3690--3699",

journal = "European journal of nuclear medicine and molecular imaging",

issn = "1619-7070",

publisher = "Springer",

number = "10",

}

Kleiburg, F, van der Hulle, T, Gelderblom, H, Slingerland, M, Speetjens, FM, Hawinkels, LJAC, Dibbets-Schneider, P, van Velden, FHP, Pool, M, Lam, SW, Bovée, JVMG, Heijmen, L & de Geus-Oei, LF 2025, 'PSMA expression and PSMA PET/CT imaging in metastatic soft tissue sarcoma patients, results of a prospective study', European journal of nuclear medicine and molecular imaging, vol. 52, no. 10, pp. 3690-3699. https://doi.org/10.1007/s00259-025-07224-z

TY - JOUR

T1 - PSMA expression and PSMA PET/CT imaging in metastatic soft tissue sarcoma patients, results of a prospective study

AU - Kleiburg, F.

AU - van der Hulle, T.

AU - Gelderblom, H.

AU - Slingerland, M.

AU - Speetjens, F. M.

AU - Hawinkels, L. J.A.C.

AU - Dibbets-Schneider, P.

AU - van Velden, F. H.P.

AU - Pool, M.

AU - Lam, S. W.

AU - Bovée, J. V.M.G.

AU - Heijmen, L.

AU - de Geus-Oei, L. F.

PY - 2025/8

Y1 - 2025/8

N2 - Purpose: Prostate-specific membrane antigen (PSMA) expression has been observed in a subset of soft tissue sarcomas, mainly in the neovascular endothelial cells. This feasibility study aimed to evaluate PSMA expression and PSMA PET/CT imaging in metastatic soft tissue sarcoma, providing important insights for potential future exploration of PSMA-targeted radioligand therapy. Methods: This prospective single-center study included adult patients with metastatic soft tissue sarcoma, with measurable disease (lesion diameter > 1 cm), available biopsy/resection material, ECOG/WHO performance status of 0–2 and either no prior systemic treatment, progressive disease during/after treatment, or stable disease/partial response with the last dose > 8 weeks prior. Immunohistochemical PSMA staining was performed on previously obtained biopsy or resection material. In case of high PSMA expression, a [18F]-JK-PSMA-7 PET/CT scan evaluated tracer uptake, with adequate uptake defined as SUVmax > 8. Results: Of 25 included patients, 11 (44%) had high PSMA expression: 4/11 leiomyosarcomas, 3/4 dedifferentiated liposarcomas, 2/5 undifferentiated pleomorphic sarcomas, 1/2 myxofibrosarcomas and 1/1 malignant peripheral nerve sheath tumour. Five of 11 patients agreed to a [18F]-JK-PSMA-7 PET/CT, of which 3 had lesions that showed adequate tracer uptake (SUVmax 10.7–16.7). However, uptake across all metastatic lesions was highly heterogeneous (median SUVmax = 3.8; range 0.5–16.7), indicating that these patients are unlikely to benefit sufficiently from PSMA-targeted therapy. The study was therefore terminated prematurely. Conclusion: PSMA expression and PSMA tracer uptake in metastatic soft tissue sarcoma were highly heterogeneous. A deeper understanding of PSMA biology and improved patient selection criteria are essential for future application of PSMA-targeted radioligand therapy in this disease. Trial registration: : clinicaltrials.gov, NCT05522257. Registered 31-08-2022.

AB - Purpose: Prostate-specific membrane antigen (PSMA) expression has been observed in a subset of soft tissue sarcomas, mainly in the neovascular endothelial cells. This feasibility study aimed to evaluate PSMA expression and PSMA PET/CT imaging in metastatic soft tissue sarcoma, providing important insights for potential future exploration of PSMA-targeted radioligand therapy. Methods: This prospective single-center study included adult patients with metastatic soft tissue sarcoma, with measurable disease (lesion diameter > 1 cm), available biopsy/resection material, ECOG/WHO performance status of 0–2 and either no prior systemic treatment, progressive disease during/after treatment, or stable disease/partial response with the last dose > 8 weeks prior. Immunohistochemical PSMA staining was performed on previously obtained biopsy or resection material. In case of high PSMA expression, a [18F]-JK-PSMA-7 PET/CT scan evaluated tracer uptake, with adequate uptake defined as SUVmax > 8. Results: Of 25 included patients, 11 (44%) had high PSMA expression: 4/11 leiomyosarcomas, 3/4 dedifferentiated liposarcomas, 2/5 undifferentiated pleomorphic sarcomas, 1/2 myxofibrosarcomas and 1/1 malignant peripheral nerve sheath tumour. Five of 11 patients agreed to a [18F]-JK-PSMA-7 PET/CT, of which 3 had lesions that showed adequate tracer uptake (SUVmax 10.7–16.7). However, uptake across all metastatic lesions was highly heterogeneous (median SUVmax = 3.8; range 0.5–16.7), indicating that these patients are unlikely to benefit sufficiently from PSMA-targeted therapy. The study was therefore terminated prematurely. Conclusion: PSMA expression and PSMA tracer uptake in metastatic soft tissue sarcoma were highly heterogeneous. A deeper understanding of PSMA biology and improved patient selection criteria are essential for future application of PSMA-targeted radioligand therapy in this disease. Trial registration: : clinicaltrials.gov, NCT05522257. Registered 31-08-2022.

KW - UT-Hybrid-D

KW - Prostate-specific membrane antigen

KW - PSMA

KW - PSMA PET/CT

KW - Soft tissue sarcoma

KW - Theranostics

KW - Molecular imaging

UR - https://www.scopus.com/pages/publications/105001481726

U2 - 10.1007/s00259-025-07224-z

DO - 10.1007/s00259-025-07224-z

M3 - Article

AN - SCOPUS:105001481726

SN - 1619-7070

VL - 52

SP - 3690

EP - 3699

JO - European journal of nuclear medicine and molecular imaging

JF - European journal of nuclear medicine and molecular imaging

IS - 10

ER -

PSMA expression and PSMA PET/CT imaging in metastatic soft tissue sarcoma patients, results of a prospective study

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Keywords

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