N-[N-[(S)-1,3-Dicarboxypropyl]Carbamoyl]-4-[18F]Fluorobenzyl-l-Cysteine, [18F]DCFBC: A New Imaging Probe for Prostate Cancer
Top Cited Papers
Open Access
- 15 May 2008
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 14 (10) , 3036-3043
- https://doi.org/10.1158/1078-0432.ccr-07-1517
Abstract
Purpose: Previously, we showed successful imaging of xenografts that express the prostate-specific membrane antigen (PSMA) using small-animal positron emission tomography (PET) and the radiolabeled PSMA inhibitor N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-S-[11C]methyl-l-cysteine. Herein, we extend that work by preparing and testing a PSMA inhibitor of the same class labeled with fluorine-18. Experimental Design:N-[N-[(S)-1,3-Dicarboxypropyl]carbamoyl]-4-[18F]fluorobenzyl-l-cysteine ([18F]DCFBC) was prepared by reacting 4-[18F]fluorobenzyl bromide with the precursor (S)-2-[3-[(R)-1-carboxy-2-mercaptoethyl]ureido]-pentanedioic acid in ammonia-saturated methanol at 60°C for 10 min followed by purification using C-18 reverse-phase semipreparative high-performance liquid chromatography. Severe combined immunodeficient mice bearing a s.c. PSMA+ PC-3 PIP tumor behind one shoulder and a PSMA− PC-3 FLU tumor behind the other shoulder were injected via the tail vein with either 1.85 MBq (50 μCi) of [18F]DCFBC for ex vivo biodistribution or 7.4 MBq (200 μCi) for imaging. For biodistribution, mice were sacrificed at 5, 15, 30, 60, and 120 min. Tumor, blood, and major organs were harvested and weighed, and radioactivity was counted. Imaging was done on the GE eXplore Vista small-animal PET scanner by collecting 12 consecutive 10-min frames. Results: Radiochemical yield for [18F]DCFBC averaged 16 ± 6% (n = 8) from 4-[18F]fluorobenzyl bromide. Specific radioactivities ranged from 13 to 133 GBq/μmol (350-3,600 Ci/mmol) with an average of 52 GBq/μmol (1,392 Ci/mmol; n = 6). Biodistribution and imaging studies showed high uptake of [18F]DCFBC in the PIP tumors with little to no uptake in FLU tumors. High radiopharmaceutical uptake was also seen in kidneys and bladder; however, washout of radioactivity from these organs was faster than from the PIP tumors. The maximum PIP tumor uptake was 8.16 ± 2.55% injected dose per gram, achieved at 60 min after injection, which decreased to 4.69 ± 0.89 at 120 min. The PIP tumor to muscle ratio was 20 at 120 min after injection. Based on the mouse biodistribution, the dose-limiting organ is the kidneys (human estimated absorbed dose: 0.05 mGy/MBq; 0.2 rad/mCi). Conclusion: [18F]DCFBC localizes to PSMA+-expressing tumors in mice, permitting imaging by small-animal PET. This new radiopharmaceutical is an attractive candidate for further studies of PET imaging of prostate cancer.Keywords
This publication has 41 references indexed in Scilit:
- A high-resolution structure of ligand-free human glutamate carboxypeptidase IIActa Crystallographica Section F Structural Biology and Crystallization Communications, 2007
- Vascular Targeted Therapy With Anti–Prostate-Specific Membrane Antigen Monoclonal Antibody J591 in Advanced Solid TumorsJournal of Clinical Oncology, 2007
- Design, synthesis and pharmacological activity of novel enantiomerically pure phosphonic acid-based NAALADase inhibitorsOrganic & Biomolecular Chemistry, 2007
- An HPLC/mass spectrometry platform for the development of multimodality contrast agents and targeted therapeutics: prostate‐specific membrane antigen small molecule derivativesContrast Media & Molecular Imaging, 2006
- Technology Insight: monoclonal antibody imaging of prostate cancerNature Reviews Endocrinology, 2006
- The neurotransmitter N-acetylaspartylglutamate in models of pain, ALS, diabetic neuropathy, CNS injury and schizophreniaTrends in Pharmacological Sciences, 2005
- Cancer Statistics, 2003CA: A Cancer Journal for Clinicians, 2003
- Molecular Cloning of a Peptidase Against N‐Acetylaspartylglutamate from a Rat Hippocampal cDNA LibraryJournal of Neurochemistry, 1997
- Immunocytochemical localization of the N‐acetyl‐aspartyl‐glutamate (NAAG) hydrolyzing enzyme N‐acetylated α‐linked acidic dipeptidase (NAALADase)Journal of Comparative Neurology, 1992
- Some amino acid esters - An improved preparative methodAustralian Journal of Chemistry, 1978