Dataset Information

18F-Positron Emitting/Trimethine Cyanine-Fluorescent Contrast for Image-Guided Prostate Cancer Management.

ABSTRACT: [18/19F]-4, an anionic GCPII/PSMA inhibitor for image-guided intervention in prostate cancer, is described. [19F]-4 is radiolabeled with a radiochemical yield that is ?27% and a molar activity of 190 ± 50 mCi/?mol in a <1 h, one-step, aqueous isotopic exchange reaction. [19F]-4 allows PSMA expression to be imaged by fluorescence (FL) and [18F]-PET. PC3-PIP (PSMA-positive, EC50 = 6.74 ± 1.33 nM) cancers are specifically delineated in mice that bear 3 million (18 mg) PC3-PIP and PC3 (control, PSMA-negative) cells. Colocalization of [18/19F]-4 PET, fluorescence, scintillated biodistribution, and PSMA expression are observed.

SUBMITTER: Kommidi H

PROVIDER: S-EPMC6263152 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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18F-Positron Emitting/Trimethine Cyanine-Fluorescent Contrast for Image-Guided Prostate Cancer Management.

Kommidi Harikrishna H Guo Hua H Nurili Fuad F Vedvyas Yogindra Y Jin Moonsoo M MM McClure Timothy D TD Ehdaie Behfar B Sayman Haluk B HB Akin Oguz O Aras Omer O Ting Richard R

Journal of medicinal chemistry 20180420 9

[18/19F]-4, an anionic GCPII/PSMA inhibitor for image-guided intervention in prostate cancer, is described. [19F]-4 is radiolabeled with a radiochemical yield that is ≥27% and a molar activity of 190 ± 50 mCi/μmol in a <1 h, one-step, aqueous isotopic exchange reaction. [19F]-4 allows PSMA expression to be imaged by fluorescence (FL) and [18F]-PET. PC3-PIP (PSMA-positive, EC50 = 6.74 ± 1.33 nM) cancers are specifically delineated in mice tha ...[more]

PMID: 29676909

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Project description:Clinical trials involving genome-edited cells are growing in popularity, where CAR-T immunotherapy and CRISPR/Cas9 editing are more recognized strategies. Genetic reporters are needed to localize the molecular events inside these cells in patients. Specifically, a nonimmunogenic genetic reporter is urgently needed as current reporters are immunogenic due to derivation from nonhuman sources. Prostate-specific membrane antigen (PSMA) is potentially nonimmunogenic due to its natural, low-level expression in select tissues (self-MHC display). PSMA overexpression on human prostate adenocarcinoma is also visible with excellent contrast. We exploit these properties in a transduced, two-component, Human-Derived, Genetic, Positron-emitting, and Fluorescent (HD-GPF) reporter system. Mechanistically analogous to the luciferase and luciferin reporter, PSMA is genetically encoded into non-PSMA expressing 8505C cells and tracked with ACUPA-Cy3-BF3, a single, systemically injected small molecule that delivers positron emitting fluoride (18F) and a fluorophore (Cy3) to report on cells expressing PSMA. PSMA-lentivirus transduced tissues become visible by Cy3 fluorescence, [18F]-positron emission tomography (PET), and ?-scintillated biodistribution. HD-GPF fluorescence is visible at subcellular resolution, while a reduced PET background is achieved in vivo, due to rapid ACUPA-Cy3-BF3 renal excretion. Co-transduction with luciferase and GFP show specific advantages over popular genetic reporters in advanced murine models including, a "mosaic" model of solid-tumor intratumoral heterogeneity and a survival model for observing postsurgical recurrence. We report an advanced genetic reporter that tracks genetically modified cells in entire animals and with subcellular resolution with PET and fluorescence, respectively. This reporter system is potentially nonimmunogenic and will therefore be useful in human studies. PSMA is a biomarker of prostate adenocarcinoma and ACUPA-Cy3-BF3 potential in radical prostatectomy is demonstrated.

Project description:Purpose(18)F-Fluciclovine (anti-1-amino-3-[(18)F]fluorocyclobutane-1-carboxylic acid) is a novel positron emission tomography (PET)/computed tomography (CT) radiotracer that has demonstrated utility for detection of prostate cancer. Our goal is to report the initial results from a randomized controlled trial of the integration of (18)F-fluciclovine PET-CT into treatment planning for defining prostate bed and lymph node target volumes.Methods and materialsWe report our initial findings from a cohort of 41 patients, of the first enrolled on a randomized controlled trial, who were randomized to the (18)F-fluciclovine arm. All patients underwent (18)F-fluciclovine PET-CT for the detection of metabolic abnormalities and high-resolution CT for treatment planning. The 2 datasets were registered first by use of a rigid registration. If soft tissue displacement was observable, the rigid registration was improved with a deformable registration. Each (18)F-fluciclovine abnormality was segmented as a percentage of the maximum standard uptake value (SUV) within a small region of interest around the lesion. The percentage best describing the SUV falloff was integrated in planning by expanding standard target volumes with the PET abnormality.ResultsIn 21 of 55 abnormalities, a deformable registration was needed to map the (18)F-fluciclovine activity into the simulation CT. The most selected percentage was 50% of maximum SUV, although values ranging from 15% to 70% were used for specific patients, illustrating the need for a per-patient selection of a threshold SUV value. The inclusion of (18)F-fluciclovine changed the planning volumes for 46 abnormalities (83%) of the total 55, with 28 (51%) located in the lymph nodes, 11 (20%) in the prostate bed, 10 (18%) in the prostate, and 6 (11%) in the seminal vesicles. Only 9 PET abnormalities were fully contained in the standard target volumes based on the CT-based segmentations and did not necessitate expansion.ConclusionsThe use of (18)F-fluciclovine in postprostatectomy radiation therapy planning was feasible and led to augmentation of the target volumes in the majority (30 of 41) of the patients studied.

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Dataset Information

18F-Positron Emitting/Trimethine Cyanine-Fluorescent Contrast for Image-Guided Prostate Cancer Management.

Publications

<sup>18</sup>F-Positron Emitting/Trimethine Cyanine-Fluorescent Contrast for Image-Guided Prostate Cancer Management.

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