Biodistribution, tumor detection, and radiation dosimetry of 18F-DCFBC, a low-molecular-weight inhibitor of prostate-specific membrane antigen, in patients with metastatic prostate cancer

Steve Y. Cho, Kenneth L. Gage, Ronnie Mease, Srinivasan Senthamizhchelvan, Daniel Holt, Akimosa Jeffrey-Kwanisai, Christopher J. Endres, Robert F Dannals, George Sgouros, Martin Lodge, Mario Eisenberger, Ronald Rodriguez, Michael A Carducci, Camilo Rojas, Barbara Slusher, Alan P. Kozikowski, Martin Gilbert Pomper

Research output: Contribution to journalArticle

Abstract

Prostate-specific membrane antigen (PSMA) is a type II integral membrane protein expressed on the surface of prostate cancer (PCa) cells, particularly in androgen-independent, advanced, and metastatic disease. Previously, we demonstrated that N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4- 18F-fluorobenzyl-L-cysteine (18F-DCFBC) could image an experimental model of PSMA-positive PCa using PET. Here, we describe the initial clinical experience and radiation dosimetry of 18F-DCFBC in men with metastatic PCa. Methods: Five patients with radiologic evidence of metastatic PCa were studied after the intravenous administration of 370 MBq (10 mCi) of 18F-DCFBC. Serial PET was performed until 2 h after administration. Time-activity curves were generated for selected normal tissues and metastatic foci. Radiation dose estimates were calculated using OLINDA/EXM 1.1. Results: Most vascular organs demonstrated a slow decrease in radioactivity concentration over time consistent with clearance from the blood pool, with primarily urinary radiotracer excretion. Thirty-two PET-positive suspected metastatic sites were identified, with 21 concordant on both PET and conventional imaging for abnormal findings compatible with metastatic disease. Of the 11 PET-positive sites not identified on conventional imaging, most were within the bone and could be considered suggestive for the detection of early bone metastases, although further validation is needed. The highest mean absorbed dose per unit administered radio-activity (μGy/MBq) was in the bladder wall (32.4), and the resultant effective dose was 19.9 ± 1.34 μSv/MBq (mean ± SD). Conclusion: Although further studies are needed for validation, our findings demonstrate the potential of 18F-DCFBC as a new positron-emitting imaging agent for the detection of metastatic PCa. This study also provides dose estimates for 18F-DCFBC that are comparable to those of other PET radiopharmaceuticals such as 18F-FDG. COPYRIGHT

Original languageEnglish (US)
Pages (from-to)1883-1891
Number of pages9
JournalJournal of Nuclear Medicine
Volume53
Issue number12
DOIs
StatePublished - Dec 1 2012

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Radiometry
Prostatic Neoplasms
Molecular Weight
Neoplasms
Bone and Bones
Radiopharmaceuticals
Validation Studies
Fluorodeoxyglucose F18
Radio
Intravenous Administration
Radioactivity
Androgens
Blood Vessels
human glutamate carboxypeptidase II
N-(N-((S)-1,3-Dicarboxypropyl)carbamoyl)-4-(18F)fluorobenzyl-L-cysteine
Membrane Proteins
Urinary Bladder
Theoretical Models
Electrons
Radiation

Keywords

  • F
  • PET/CT
  • Prostate cancer
  • Prostate-specific membrane antigen
  • Urea

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

@article{fb676174af3746e7b25d091ea113a5ea,
title = "Biodistribution, tumor detection, and radiation dosimetry of 18F-DCFBC, a low-molecular-weight inhibitor of prostate-specific membrane antigen, in patients with metastatic prostate cancer",
abstract = "Prostate-specific membrane antigen (PSMA) is a type II integral membrane protein expressed on the surface of prostate cancer (PCa) cells, particularly in androgen-independent, advanced, and metastatic disease. Previously, we demonstrated that N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4- 18F-fluorobenzyl-L-cysteine (18F-DCFBC) could image an experimental model of PSMA-positive PCa using PET. Here, we describe the initial clinical experience and radiation dosimetry of 18F-DCFBC in men with metastatic PCa. Methods: Five patients with radiologic evidence of metastatic PCa were studied after the intravenous administration of 370 MBq (10 mCi) of 18F-DCFBC. Serial PET was performed until 2 h after administration. Time-activity curves were generated for selected normal tissues and metastatic foci. Radiation dose estimates were calculated using OLINDA/EXM 1.1. Results: Most vascular organs demonstrated a slow decrease in radioactivity concentration over time consistent with clearance from the blood pool, with primarily urinary radiotracer excretion. Thirty-two PET-positive suspected metastatic sites were identified, with 21 concordant on both PET and conventional imaging for abnormal findings compatible with metastatic disease. Of the 11 PET-positive sites not identified on conventional imaging, most were within the bone and could be considered suggestive for the detection of early bone metastases, although further validation is needed. The highest mean absorbed dose per unit administered radio-activity (μGy/MBq) was in the bladder wall (32.4), and the resultant effective dose was 19.9 ± 1.34 μSv/MBq (mean ± SD). Conclusion: Although further studies are needed for validation, our findings demonstrate the potential of 18F-DCFBC as a new positron-emitting imaging agent for the detection of metastatic PCa. This study also provides dose estimates for 18F-DCFBC that are comparable to those of other PET radiopharmaceuticals such as 18F-FDG. COPYRIGHT",
keywords = "F, PET/CT, Prostate cancer, Prostate-specific membrane antigen, Urea",
author = "Cho, {Steve Y.} and Gage, {Kenneth L.} and Ronnie Mease and Srinivasan Senthamizhchelvan and Daniel Holt and Akimosa Jeffrey-Kwanisai and Endres, {Christopher J.} and Dannals, {Robert F} and George Sgouros and Martin Lodge and Mario Eisenberger and Ronald Rodriguez and Carducci, {Michael A} and Camilo Rojas and Barbara Slusher and Kozikowski, {Alan P.} and Pomper, {Martin Gilbert}",
year = "2012",
month = "12",
day = "1",
doi = "10.2967/jnumed.112.104661",
language = "English (US)",
volume = "53",
pages = "1883--1891",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "Society of Nuclear Medicine Inc.",
number = "12",

}

TY - JOUR

T1 - Biodistribution, tumor detection, and radiation dosimetry of 18F-DCFBC, a low-molecular-weight inhibitor of prostate-specific membrane antigen, in patients with metastatic prostate cancer

AU - Cho, Steve Y.

AU - Gage, Kenneth L.

AU - Mease, Ronnie

AU - Senthamizhchelvan, Srinivasan

AU - Holt, Daniel

AU - Jeffrey-Kwanisai, Akimosa

AU - Endres, Christopher J.

AU - Dannals, Robert F

AU - Sgouros, George

AU - Lodge, Martin

AU - Eisenberger, Mario

AU - Rodriguez, Ronald

AU - Carducci, Michael A

AU - Rojas, Camilo

AU - Slusher, Barbara

AU - Kozikowski, Alan P.

AU - Pomper, Martin Gilbert

PY - 2012/12/1

Y1 - 2012/12/1

N2 - Prostate-specific membrane antigen (PSMA) is a type II integral membrane protein expressed on the surface of prostate cancer (PCa) cells, particularly in androgen-independent, advanced, and metastatic disease. Previously, we demonstrated that N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4- 18F-fluorobenzyl-L-cysteine (18F-DCFBC) could image an experimental model of PSMA-positive PCa using PET. Here, we describe the initial clinical experience and radiation dosimetry of 18F-DCFBC in men with metastatic PCa. Methods: Five patients with radiologic evidence of metastatic PCa were studied after the intravenous administration of 370 MBq (10 mCi) of 18F-DCFBC. Serial PET was performed until 2 h after administration. Time-activity curves were generated for selected normal tissues and metastatic foci. Radiation dose estimates were calculated using OLINDA/EXM 1.1. Results: Most vascular organs demonstrated a slow decrease in radioactivity concentration over time consistent with clearance from the blood pool, with primarily urinary radiotracer excretion. Thirty-two PET-positive suspected metastatic sites were identified, with 21 concordant on both PET and conventional imaging for abnormal findings compatible with metastatic disease. Of the 11 PET-positive sites not identified on conventional imaging, most were within the bone and could be considered suggestive for the detection of early bone metastases, although further validation is needed. The highest mean absorbed dose per unit administered radio-activity (μGy/MBq) was in the bladder wall (32.4), and the resultant effective dose was 19.9 ± 1.34 μSv/MBq (mean ± SD). Conclusion: Although further studies are needed for validation, our findings demonstrate the potential of 18F-DCFBC as a new positron-emitting imaging agent for the detection of metastatic PCa. This study also provides dose estimates for 18F-DCFBC that are comparable to those of other PET radiopharmaceuticals such as 18F-FDG. COPYRIGHT

AB - Prostate-specific membrane antigen (PSMA) is a type II integral membrane protein expressed on the surface of prostate cancer (PCa) cells, particularly in androgen-independent, advanced, and metastatic disease. Previously, we demonstrated that N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4- 18F-fluorobenzyl-L-cysteine (18F-DCFBC) could image an experimental model of PSMA-positive PCa using PET. Here, we describe the initial clinical experience and radiation dosimetry of 18F-DCFBC in men with metastatic PCa. Methods: Five patients with radiologic evidence of metastatic PCa were studied after the intravenous administration of 370 MBq (10 mCi) of 18F-DCFBC. Serial PET was performed until 2 h after administration. Time-activity curves were generated for selected normal tissues and metastatic foci. Radiation dose estimates were calculated using OLINDA/EXM 1.1. Results: Most vascular organs demonstrated a slow decrease in radioactivity concentration over time consistent with clearance from the blood pool, with primarily urinary radiotracer excretion. Thirty-two PET-positive suspected metastatic sites were identified, with 21 concordant on both PET and conventional imaging for abnormal findings compatible with metastatic disease. Of the 11 PET-positive sites not identified on conventional imaging, most were within the bone and could be considered suggestive for the detection of early bone metastases, although further validation is needed. The highest mean absorbed dose per unit administered radio-activity (μGy/MBq) was in the bladder wall (32.4), and the resultant effective dose was 19.9 ± 1.34 μSv/MBq (mean ± SD). Conclusion: Although further studies are needed for validation, our findings demonstrate the potential of 18F-DCFBC as a new positron-emitting imaging agent for the detection of metastatic PCa. This study also provides dose estimates for 18F-DCFBC that are comparable to those of other PET radiopharmaceuticals such as 18F-FDG. COPYRIGHT

KW - F

KW - PET/CT

KW - Prostate cancer

KW - Prostate-specific membrane antigen

KW - Urea

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U2 - 10.2967/jnumed.112.104661

DO - 10.2967/jnumed.112.104661

M3 - Article

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AN - SCOPUS:84870340190

VL - 53

SP - 1883

EP - 1891

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

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