GRPr antagonist 68Ga‐SB3 PET/CT‐imaging of primary prostate cancer in therapy-naive patients

Ingrid L. Bakker; Alida C. Fröberg; Martijn B. Busstra; J. Fred Verzijlbergen; Mark Konijnenberg; Geert J.L.H. van Leenders; Ivo G. Schoots; Erik de Blois; Wytske M. van Weerden; Simone U. Dalm; Theodosia Maina; Berthold A. Nock; Marion de Jong

doi:10.2967/jnumed.120.258814

GRPr antagonist ⁶⁸Ga‐SB3 PET/CT‐imaging of primary prostate cancer in therapy-naive patients

Ingrid L. Bakker, Alida C. Fröberg, Martijn B. Busstra, J. Fred Verzijlbergen, Mark Konijnenberg, Geert J.L.H. van Leenders, Ivo G. Schoots, Erik de Blois, Wytske M. van Weerden, Simone U. Dalm, Theodosia Maina, Berthold A. Nock, Marion de Jong^*

^*Corresponding author for this work

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

22 Citations (Scopus)

Abstract

The gastrin releasing peptide receptor (GRPr) is overexpressed in prostate cancer (PCa) cells, making it an excellent tool for targeted imaging. The gallium-68 labeled GRPr antagonist SB3 (⁶⁸Ga-SB3) has shown excellent results in (pre)clinical studies and was selected for further clinical investigation. The aims of this phase I study were to investigate ⁶⁸Ga-SB3 PET/CT-imaging of primary PCa tumors and assess safety. More aims included biodistribution, dosimetry, comparison with pathology and GRPr expression. MATERIALS AND METHODS: Ten therapy-naive, biopsy-confirmed PCa patients planned for prostatectomy were included. A 3-hour extensive PET/CT-imaging protocol was performed, within 2 weeks prior to prostatectomy. Prostate tissue was evaluated for tumor localization, Gleason Score and in vitro autoradiography was performed to determine GRPr expression. Available MRI scans performed within 3 months prior to the study were matched. For dosimetry residence times were estimated and effective dose to the body as well as absorbed doses to organs were calculated using the IDAC dose 2.1 model. RESULTS: Administration of 68Ga-SB3 (187.4 ± 40.0 MBq, 40±5 μg) was well tolerated, no significant changes in vital signs or laboratory results were observed. 68Ga-SB3 PET/CT showed lesions in 8 out of 10 patients. Pathological analysis revealed a total of 16 tumor lesions of which PET/CT showed 14, resulting in a sensitivity of 88%. ⁶⁸Ga-SB3 PET/CT-imaging showed uptake in 2 large prostatic intraepithelial neoplasia foci, considered a precursor of PCa, resulting in an 88% specificity. Autoradiography of tumor lesions revealed heterogeneous GRPr expression and was negative in 4 patients. Both PET/CT-negative patients had a GRPr-negative tumor. In autoradiography-positive tumors, level of GRPr expression showed significant correlation to tracer uptake on PET/CT. Dosimetry calculations estimated the effective dose to be 0.0144 mSv/MBq, similar to other 68Ga labeled radiopeptides. Highest absorbed dose was detected in the physiological GRPr-expressing pancreas (0.198 mGy/MBq), followed by bladder wall and kidneys. CONCLUSION: 68Ga-SB3 PET/CT is a safe imaging method and a promising tool for early PCa imaging.

Original language	English
Journal	Journal of Nuclear Medicine
Volume	62
Issue number	11
DOIs	https://doi.org/10.2967/jnumed.120.258814
Publication status	Published - 1 Nov 2021

Bibliographical note

Funding Information:
The authors would like to thank all employees of the department of Radiology and Nuclear Medicine at Erasmus for their collaborative effort to realize this locally sponsored radiolabeled drug research. In particular W.A.P. Breeman P.J.J.M. Janssen and M. van der Meij aiding in IMPD and IB completion, J. Teunissen our independent physician, the scan team: F. van der Pluijm, G. Caan, T. Cox and A.S. Almeida. We thank H. Voorwinden and J. de Swart for radiation protection advice and the whole radiolabeling team for their efforts and the Radiology Trial Office for monitoring. Special thanks to E. Holleman for insights in interpreting pathology data.

Publisher Copyright:
© 2021 Society of Nuclear Medicine Inc.. All rights reserved.

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Cite this

Bakker, I. L., Fröberg, A. C., Busstra, M. B., Verzijlbergen, J. F., Konijnenberg, M., van Leenders, G. J. L. H., Schoots, I. G., de Blois, E., van Weerden, W. M., Dalm, S. U., Maina, T., Nock, B. A., & de Jong, M. (2021). GRPr antagonist ⁶⁸Ga‐SB3 PET/CT‐imaging of primary prostate cancer in therapy-naive patients. Journal of Nuclear Medicine, 62(11). https://doi.org/10.2967/jnumed.120.258814

@article{1ad40c87e934464a9a751afda9920be6,

title = "GRPr antagonist 68Ga‐SB3 PET/CT‐imaging of primary prostate cancer in therapy-naive patients",

abstract = "The gastrin releasing peptide receptor (GRPr) is overexpressed in prostate cancer (PCa) cells, making it an excellent tool for targeted imaging. The gallium-68 labeled GRPr antagonist SB3 (68Ga-SB3) has shown excellent results in (pre)clinical studies and was selected for further clinical investigation. The aims of this phase I study were to investigate 68Ga-SB3 PET/CT-imaging of primary PCa tumors and assess safety. More aims included biodistribution, dosimetry, comparison with pathology and GRPr expression. MATERIALS AND METHODS: Ten therapy-naive, biopsy-confirmed PCa patients planned for prostatectomy were included. A 3-hour extensive PET/CT-imaging protocol was performed, within 2 weeks prior to prostatectomy. Prostate tissue was evaluated for tumor localization, Gleason Score and in vitro autoradiography was performed to determine GRPr expression. Available MRI scans performed within 3 months prior to the study were matched. For dosimetry residence times were estimated and effective dose to the body as well as absorbed doses to organs were calculated using the IDAC dose 2.1 model. RESULTS: Administration of 68Ga-SB3 (187.4 ± 40.0 MBq, 40±5 μg) was well tolerated, no significant changes in vital signs or laboratory results were observed. 68Ga-SB3 PET/CT showed lesions in 8 out of 10 patients. Pathological analysis revealed a total of 16 tumor lesions of which PET/CT showed 14, resulting in a sensitivity of 88%. 68Ga-SB3 PET/CT-imaging showed uptake in 2 large prostatic intraepithelial neoplasia foci, considered a precursor of PCa, resulting in an 88% specificity. Autoradiography of tumor lesions revealed heterogeneous GRPr expression and was negative in 4 patients. Both PET/CT-negative patients had a GRPr-negative tumor. In autoradiography-positive tumors, level of GRPr expression showed significant correlation to tracer uptake on PET/CT. Dosimetry calculations estimated the effective dose to be 0.0144 mSv/MBq, similar to other 68Ga labeled radiopeptides. Highest absorbed dose was detected in the physiological GRPr-expressing pancreas (0.198 mGy/MBq), followed by bladder wall and kidneys. CONCLUSION: 68Ga-SB3 PET/CT is a safe imaging method and a promising tool for early PCa imaging.",

author = "Bakker, {Ingrid L.} and Fr{\"o}berg, {Alida C.} and Busstra, {Martijn B.} and Verzijlbergen, {J. Fred} and Mark Konijnenberg and {van Leenders}, {Geert J.L.H.} and Schoots, {Ivo G.} and {de Blois}, Erik and {van Weerden}, {Wytske M.} and Dalm, {Simone U.} and Theodosia Maina and Nock, {Berthold A.} and {de Jong}, Marion",

note = "Funding Information: The authors would like to thank all employees of the department of Radiology and Nuclear Medicine at Erasmus for their collaborative effort to realize this locally sponsored radiolabeled drug research. In particular W.A.P. Breeman P.J.J.M. Janssen and M. van der Meij aiding in IMPD and IB completion, J. Teunissen our independent physician, the scan team: F. van der Pluijm, G. Caan, T. Cox and A.S. Almeida. We thank H. Voorwinden and J. de Swart for radiation protection advice and the whole radiolabeling team for their efforts and the Radiology Trial Office for monitoring. Special thanks to E. Holleman for insights in interpreting pathology data. Publisher Copyright: {\textcopyright} 2021 Society of Nuclear Medicine Inc.. All rights reserved.",

year = "2021",

month = nov,

day = "1",

doi = "10.2967/jnumed.120.258814",

language = "English",

volume = "62",

journal = "Journal of Nuclear Medicine",

issn = "0161-5505",

publisher = "Society of Nuclear Medicine and Molecular Imaging",

number = "11",

}

Bakker, IL, Fröberg, AC, Busstra, MB, Verzijlbergen, JF, Konijnenberg, M , van Leenders, GJLH , Schoots, IG , de Blois, E , van Weerden, WM , Dalm, SU, Maina, T, Nock, BA & de Jong, M 2021, 'GRPr antagonist ⁶⁸Ga‐SB3 PET/CT‐imaging of primary prostate cancer in therapy-naive patients', Journal of Nuclear Medicine, vol. 62, no. 11. https://doi.org/10.2967/jnumed.120.258814

TY - JOUR

T1 - GRPr antagonist 68Ga‐SB3 PET/CT‐imaging of primary prostate cancer in therapy-naive patients

AU - Bakker, Ingrid L.

AU - Fröberg, Alida C.

AU - Busstra, Martijn B.

AU - Verzijlbergen, J. Fred

AU - Konijnenberg, Mark

AU - van Leenders, Geert J.L.H.

AU - Schoots, Ivo G.

AU - de Blois, Erik

AU - van Weerden, Wytske M.

AU - Dalm, Simone U.

AU - Maina, Theodosia

AU - Nock, Berthold A.

AU - de Jong, Marion

N1 - Funding Information: The authors would like to thank all employees of the department of Radiology and Nuclear Medicine at Erasmus for their collaborative effort to realize this locally sponsored radiolabeled drug research. In particular W.A.P. Breeman P.J.J.M. Janssen and M. van der Meij aiding in IMPD and IB completion, J. Teunissen our independent physician, the scan team: F. van der Pluijm, G. Caan, T. Cox and A.S. Almeida. We thank H. Voorwinden and J. de Swart for radiation protection advice and the whole radiolabeling team for their efforts and the Radiology Trial Office for monitoring. Special thanks to E. Holleman for insights in interpreting pathology data. Publisher Copyright: © 2021 Society of Nuclear Medicine Inc.. All rights reserved.

PY - 2021/11/1

Y1 - 2021/11/1

N2 - The gastrin releasing peptide receptor (GRPr) is overexpressed in prostate cancer (PCa) cells, making it an excellent tool for targeted imaging. The gallium-68 labeled GRPr antagonist SB3 (68Ga-SB3) has shown excellent results in (pre)clinical studies and was selected for further clinical investigation. The aims of this phase I study were to investigate 68Ga-SB3 PET/CT-imaging of primary PCa tumors and assess safety. More aims included biodistribution, dosimetry, comparison with pathology and GRPr expression. MATERIALS AND METHODS: Ten therapy-naive, biopsy-confirmed PCa patients planned for prostatectomy were included. A 3-hour extensive PET/CT-imaging protocol was performed, within 2 weeks prior to prostatectomy. Prostate tissue was evaluated for tumor localization, Gleason Score and in vitro autoradiography was performed to determine GRPr expression. Available MRI scans performed within 3 months prior to the study were matched. For dosimetry residence times were estimated and effective dose to the body as well as absorbed doses to organs were calculated using the IDAC dose 2.1 model. RESULTS: Administration of 68Ga-SB3 (187.4 ± 40.0 MBq, 40±5 μg) was well tolerated, no significant changes in vital signs or laboratory results were observed. 68Ga-SB3 PET/CT showed lesions in 8 out of 10 patients. Pathological analysis revealed a total of 16 tumor lesions of which PET/CT showed 14, resulting in a sensitivity of 88%. 68Ga-SB3 PET/CT-imaging showed uptake in 2 large prostatic intraepithelial neoplasia foci, considered a precursor of PCa, resulting in an 88% specificity. Autoradiography of tumor lesions revealed heterogeneous GRPr expression and was negative in 4 patients. Both PET/CT-negative patients had a GRPr-negative tumor. In autoradiography-positive tumors, level of GRPr expression showed significant correlation to tracer uptake on PET/CT. Dosimetry calculations estimated the effective dose to be 0.0144 mSv/MBq, similar to other 68Ga labeled radiopeptides. Highest absorbed dose was detected in the physiological GRPr-expressing pancreas (0.198 mGy/MBq), followed by bladder wall and kidneys. CONCLUSION: 68Ga-SB3 PET/CT is a safe imaging method and a promising tool for early PCa imaging.

AB - The gastrin releasing peptide receptor (GRPr) is overexpressed in prostate cancer (PCa) cells, making it an excellent tool for targeted imaging. The gallium-68 labeled GRPr antagonist SB3 (68Ga-SB3) has shown excellent results in (pre)clinical studies and was selected for further clinical investigation. The aims of this phase I study were to investigate 68Ga-SB3 PET/CT-imaging of primary PCa tumors and assess safety. More aims included biodistribution, dosimetry, comparison with pathology and GRPr expression. MATERIALS AND METHODS: Ten therapy-naive, biopsy-confirmed PCa patients planned for prostatectomy were included. A 3-hour extensive PET/CT-imaging protocol was performed, within 2 weeks prior to prostatectomy. Prostate tissue was evaluated for tumor localization, Gleason Score and in vitro autoradiography was performed to determine GRPr expression. Available MRI scans performed within 3 months prior to the study were matched. For dosimetry residence times were estimated and effective dose to the body as well as absorbed doses to organs were calculated using the IDAC dose 2.1 model. RESULTS: Administration of 68Ga-SB3 (187.4 ± 40.0 MBq, 40±5 μg) was well tolerated, no significant changes in vital signs or laboratory results were observed. 68Ga-SB3 PET/CT showed lesions in 8 out of 10 patients. Pathological analysis revealed a total of 16 tumor lesions of which PET/CT showed 14, resulting in a sensitivity of 88%. 68Ga-SB3 PET/CT-imaging showed uptake in 2 large prostatic intraepithelial neoplasia foci, considered a precursor of PCa, resulting in an 88% specificity. Autoradiography of tumor lesions revealed heterogeneous GRPr expression and was negative in 4 patients. Both PET/CT-negative patients had a GRPr-negative tumor. In autoradiography-positive tumors, level of GRPr expression showed significant correlation to tracer uptake on PET/CT. Dosimetry calculations estimated the effective dose to be 0.0144 mSv/MBq, similar to other 68Ga labeled radiopeptides. Highest absorbed dose was detected in the physiological GRPr-expressing pancreas (0.198 mGy/MBq), followed by bladder wall and kidneys. CONCLUSION: 68Ga-SB3 PET/CT is a safe imaging method and a promising tool for early PCa imaging.

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