Purpose Prostate-specific membrane antigen (PSMA) is a recognized target for imaging prostate cancer. Here we present initial safety, biodistribution, and radiation dosimetry results with [18F]DCFPyL, a second-generation fluorine-18-labeled small-molecule PSMA inhibitor, in patients with prostate cancer. Procedures Biodistribution was evaluated using sequential positron-emission tomography (PET) scans in nine patients with prostate cancer. Time-activity curves from the most avid tumor foci were determined. The radiation dose to selected organs was estimated using OLINDA/EXM. Results No major radiotracer-specific adverse events were observed. Physiologic accumulation was observed in known sites of PSMA expression. Accumulation in putative sites of prostate cancer was observed (SUVmax up to >100, and tumor-to-blood ratios up to >50). The effective radiation dose from [18F]DCFPyL was 0.0139 mGy/MBq or 5 mGy (0.5 rem) from an injected dose of 370 MBq (10 mCi). Conclusions [18F]DCFPyL is safe with biodistribution as expected, and its accumulation is high in presumed primary and metastatic foci. The radiation dose from [18F]DCFPyL is similar to that from other PET radiotracers.
We describe a new imaging method for detecting prostate cancer, whether localized or disseminated and metastatic to soft tissues and bone. The method relies on the use of imaging reporter genes under the control of the promoter of AEG-1 (MTDH), which is selectively active only in malignant cells. Through systemic, nanoparticle-based delivery of the imaging construct, lesions can be identified through bioluminescence imaging and single photon emission-computed tomography in the PC3-ML murine model of prostate cancer at high sensitivity. This approach is applicable for the detection of prostate cancer metastases, including bone lesions for which there is no current reliable agent for non-invasive clinical imaging. Further, the approach compares favorably to accepted and emerging clinical standards, including positron emission tomography with [18F]fluorodeoxyglucose and [18F]sodium fluoride. Our results offer a preclinical proof of concept that rationalizes clinical evaluation in patients with advanced prostate cancer.
Objective A series of renal hybrid oncocytic/chromophobe tumors (HOCTs) was retrospectively assessed for morphologic features and enhancement characteristics by computed tomography (CT). Materials (Subjects) and Methods Nine patients with pathologically proven HOCTs were identified. These patients harbored a total of 12 lesions. All patients had available preoperative contrast-enhanced CT examinations, although a proportion of the studies had been carried out at outside institutions. The morphologic characteristics and enhancement patterns of each tumor were evaluated systematically. Results Seventy-eight percent of the patients were men, with a mean age of 62 years. None of the patients had evidence of metastatic disease at the time of surgery. Mean tumor diameter was 4.4 cm. All the lesions were solid and well circumscribed. Calcifications were not seen in any of these masses. Thirty-three percent of the tumors demonstrated a central stellate hypodensity pattern, whereas a further 42% of the tumors demonstrated a heterogenous appearance. Mean attenuation values were 25.7 HU (noncontrast), 77.4 HU (arterial), 124.8 HU (venous), and 76.8 HU (delayed). Tumor-to-cortex ratios for the 2 enhanced phases (arterial and venous) were 0.56 and 0.79, respectively. Conclusions A series of HOCTs were found on CT to have 2 distinct patterns—a heterogenous enhancement pattern and an “oncocytoma-like” pattern with a central stellate hypodensity. Although the prospective diagnosis of HOCTs on the basis of CT findings is unlikely, an awareness of the existence of these lesions is important as new means of characterizing renal masses on imaging arise.
<p>S1: Schematic maps of AEG-Prom and PEG-Prom reporter constructs S2: c-MYC protein levels analyzed in prostate cancer cell lines by western blotting using anti-MYC antibody (57-70 kDa) S3: Time course for model maturation with PC3-ML-Luc cells using bioluminescence imaging (BLI) at week 5 after injection of: (A) 5 x 104 cells (intracardiac); (B) 1 x 106 cells (tail vein) S4: Cancer-specific AEG-Prom and PEG-Prom activity shown by bioluminescence imaging (BLI) in an experimental model of human prostate cancer (PC3-ML) S5: Comparison of Luc plasmid delivery to lungs of the PCa group for pAEG-Luc treated and pPEG-Luc treated animals (n = 3, PCa-1-3 in Supplemental Fig. S4), respectively S6: Correlation between AEG-1 promoter-driven Luc expression and metastatic sites by histopathological analysis in a bone metastatic prostate cancer model of prostate cancer metastasis S7: Cancer-Specific AEG-Prom activity shown by bioluminescence imaging (BLI) in experimental models of human prostate cancer (PC3-ML) S8: AEG-Prom-based SPECT/CT imaging detects distant metastasis not identified by NaF- or FDG-PET/CT</p>
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