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1.
Mol Imaging Biol ; 24(4): 651-658, 2022 08.
Article in English | MEDLINE | ID: mdl-35349039

ABSTRACT

AIM/PURPOSE: Fibroblast activation protein-(FAP)-ligands, a novel class of tracers for PET/CT imaging, demonstrated promising results in previous studies in various malignancies compared to standard [18F]FDG PET/CT. 68Ga-labeled fibroblast activation protein inhibitor-([68Ga]Ga-DOTA-FAPI)-PET/CT impresses with sharp contrasts in terms of high tumor uptake and low background noise leading to clear delineation. [18F]FDG PET/CT has limited accuracy in bladder cancer due to high background signal. Therefore, we sought to evaluate the diagnostic potential of [68Ga]FAPI in patients with bladder cancer. MATERIAL AND METHODS: This retrospective analysis consisted of 8 patients (median age 66), 7 of whom underwent both [68Ga]FAPI and [18F]FDG PET/CT scans with a median time interval of 5 days (range 1-20 days). Quantification of tracer uptake was determined with SUVmax and SUVmean. Furthermore, the tumor-to-background ratio (TBR) was derived by dividing the SUVmax of tumor lesions by the SUVmax of adipose tissue, skeletal muscle, and blood pool. RESULTS: Overall, 31 metastases were detected in five patients including lymph node metastases (n = 23), bone metastases (n = 4), lung metastases (n = 3), and a peritoneal metastasis (n = 1). In one patient, [68Ga]FAPI demonstrated significant uptake in the primary tumor located in the bladder wall. [68Ga]FAPI-PET/CT demonstrated significantly higher uptake compared to [18F]FDG PET/CT with higher mean SUVmax (8.2 vs. 4.6; p = 0.01). Furthermore, [68Ga]FAPI detected additional 30% (n = 9) lesions, missed by [18F]FDG. TBR demonstrated favorable uptake for [68Ga]FAPI in comparison to [18F]FDG. Significant differences were determined with regard to metastasis/blood pool ([68Ga]FAPI 5.3 vs [18F]FDG 1.9; p = 0.001). CONCLUSION: [68Ga]FAPI-PET/CT is a promising diagnostic radioligand for patients with bladder cancer. This first described analysis of FAP-ligand in bladder cancer revealed superiority over [18F]FDG in a small patient cohort. Thus, this so far assumed potential has to be confirmed and extended by larger and prospective studies.


Subject(s)
Positron Emission Tomography Computed Tomography , Urinary Bladder Neoplasms , Aged , Fluorodeoxyglucose F18 , Gallium Radioisotopes , Humans , Positron Emission Tomography Computed Tomography/methods , Prospective Studies , Retrospective Studies , Urinary Bladder Neoplasms/diagnostic imaging
2.
Mol Imaging Biol ; 22(6): 1495-1500, 2020 12.
Article in English | MEDLINE | ID: mdl-33063132

ABSTRACT

PURPOSE: Quinoline-based ligands targeting cancer-associated fibroblasts have emerged as promising radiopharmaceuticals in different tumor entities. The aim of this retrospective study was to explore the potential of FAPI-PET/CT in the initial staging of esophageal cancer patients and its usefulness in radiotherapy planning as a first clinical analysis. METHODS: Seven patients with treatment-naive esophageal cancer underwent FAPI-PET/CT. Tracer uptake was quantified by standardized uptake values (SUV)max and (SUV)mean. Six patients received definitive and one neoadjuvant (chemo)radiation therapy. Endo-esophageal clipping, the gold standard to define tumor margins not delineable per CT, was performed in three patients. RESULTS: Primary tumors demonstrated high FAPI uptake with a median SUVmax of 17.2. Excellent tumor-to-background ratios resulted in accurate target volume delineation and were found in perfect match with clipping. Detection of regional lymph node metastases facilitated the use of simultaneous integrated boost radiotherapy plans for these patients. CONCLUSION: FAPI-PET/CT may be beneficial for the management of esophageal cancer particularly in planning radiotherapy, but further research is necessary to increase patient number and statistical reliability.


Subject(s)
Enzyme Inhibitors/metabolism , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/radiotherapy , Fibroblasts/metabolism , Positron Emission Tomography Computed Tomography , Radiotherapy Planning, Computer-Assisted , Aged , Aged, 80 and over , Esophageal Neoplasms/pathology , Female , Humans , Male , Middle Aged , Neoplasm Staging
3.
Clin Radiol ; 74(11): 841-852, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31239107

ABSTRACT

Multiparametric (mp) prostate magnetic resonance imaging (MRI) is playing an increasingly prominent role in the diagnostic work-up of patients with suspected prostate cancer. Performing mpMRI before biopsy offers several advantages including biopsy avoidance under certain clinical circumstances and targeting biopsy of suspicious lesions to enable the correct diagnosis. The success of the technique is heavily dependent on high-quality image acquisition, interpretation, and report communication, all areas addressed by previous versions of the Prostate Imaging-Reporting and Data System (PI-RADS) recommendations. Numerous studies have validated the approach, but the widespread adoption of PI-RADS version 2 has also highlighted inconsistencies and limitations, particularly relating to interobserver variability for evaluation of the transition zone. These limitations are addressed in the recently released version 2.1. In this article, we highlight the key changes proposed in PI-RADS v2.1 and explore the background reasoning and evidence for the recommendations.


Subject(s)
Multiparametric Magnetic Resonance Imaging/methods , Prostatic Neoplasms/pathology , Aged , Humans , Imaging, Three-Dimensional , Male , Middle Aged , Neoplasm Staging , Radiology Information Systems , Sensitivity and Specificity
4.
J Transl Sci ; 5(2)2019 Apr.
Article in English | MEDLINE | ID: mdl-30906574

ABSTRACT

INTRODUCTION: Tumors over-expressing the human epithelial receptor 2 (HER2) or exhibiting amplification or mutation of its proto-oncogene have a poorer prognosis. Using trastuzumab and/or other HER2 targeted therapies can increase overall survival in patients with HER2(+) tumors making it critical to accurately identify patients who may benefit. We report on a Phase 0 study of the imaging agent, 111In-CHX-A"-DTPA trastuzumab, in patients with known HER2 status to evaluate its safety and biodistribution and to obtain preliminary data regarding its ability to provide an accurate, whole-body, non-invasive means to determine HER2 status. METHODS: 111In-CHX-A"-DTPA trastuzumab was radiolabeled on-site and slowly infused into 11 patients who underwent single (n=5) or multiple (n=6) ɣ-camera (n=6) and/or SPECT (n=8) imaging sessions. RESULTS: No safety issues were identified. Visual and semi-quantitative imaging data were concordant with tissue HER2 expression profiling in all but 1 patient. The biodistribution showed intense peak liver activity at the initial imaging timepoint (3.3h) and a single-phase clearance fit of the average time-activity curve (TAC) estimated t1/2=46.9h (R2=0.97; 95%CI 41.8 to 53h). This was followed by high gastrointestinal (GI) tract activity peaking by 52h. Linear regression predicted GI clearance by 201.2h (R2 =0.96; 95%CI 188.5 to 216.9h). Blood pool had lower activity with its maximum on the initial images. Non-linear regression fit projected a t1/2=34.2h (R2 =0.96; 95%CI 25.3 to 46.3h). Assuming linear whole-body clearance, linear regression projected complete elimination (x-intercept) at 256.5hr (R2=0.96; 95%CI 186.1 to 489.2h). CONCLUSION: 111In-CHX-A"-DTPA trastuzumab can be safely imaged in humans. The biodistribution allowed for visual and semiquantitative analysis with results concordant with tissue expression profiling in 10 of 11 patients. Advances in Knowledge and Implications for Patient Care Using readily available components and on-site radiolabeling 111In-CHX-A"-DTPA trastuzumab SPECT imaging may provide an economical, non-invasive means to detect HER2 over-expression.

5.
World J Urol ; 37(10): 2147-2153, 2019 Oct.
Article in English | MEDLINE | ID: mdl-30671638

ABSTRACT

PURPOSE: To define the role of focal laser ablation (FLA) as clinical treatment of prostate cancer (PCa) using the Delphi consensus method. METHODS: A panel of international experts in the field of focal therapy (FT) in PCa conducted a collaborative consensus project using the Delphi method. Experts were invited to online questionnaires focusing on patient selection and treatment of PCa with FLA during four subsequent rounds. After each round, outcomes were displayed, and questionnaires were modified based on the comments provided by panelists. Results were finalized and discussed during face-to-face meetings. RESULTS: Thirty-seven experts agreed to participate, and consensus was achieved on 39/43 topics. Clinically significant PCa (csPCa) was defined as any volume Grade Group 2 [Gleason score (GS) 3+4]. Focal therapy was specified as treatment of all csPCa and can be considered primary treatment as an alternative to radical treatment in carefully selected patients. In patients with intermediate-risk PCa (GS 3+4) as well as patients with MRI-visible and biopsy-confirmed local recurrence, FLA is optimal for targeted ablation of a specific magnetic resonance imaging (MRI)-visible focus. However, FLA should not be applied to candidates for active surveillance and close follow-up is required. Suitability for FLA is based on tumor volume, location to vital structures, GS, MRI-visibility, and biopsy confirmation. CONCLUSION: Focal laser ablation is a promising technique for treatment of clinically localized PCa and should ideally be performed within approved clinical trials. So far, only few studies have reported on FLA and further validation with longer follow-up is mandatory before widespread clinical implementation is justified.


Subject(s)
Laser Therapy , Prostatectomy/methods , Prostatic Neoplasms/surgery , Delphi Technique , Humans , Laser Therapy/standards , Male , Practice Guidelines as Topic , Prostatectomy/standards
6.
Prostate Cancer Prostatic Dis ; 20(3): 348-351, 2017 09.
Article in English | MEDLINE | ID: mdl-28440325

ABSTRACT

BACKGROUND: Analysis of systematic 12-core biopsies (SBx) has shown that African-American (AA) men tend to harbor higher risk prostate cancer (PCa) at presentation relative to other races. Multiparametric magnetic resonance imaging (mpMRI) and MRI-ultrasound fusion-guided biopsy (FBx) have been shown to diagnose more intermediate- and high-risk PCa in the general population; however, the efficacy in AA remains largely uncharacterized. We aim to evaluate the utility of FBx in an AA patient cohort. METHODS: Men suspected of PCa underwent an mpMRI and FBx with concurrent SBx from 2007 to 2015 in this institutional review board-approved prospective cohort study. Patient demographics, imaging and fusion biopsy variables were collected. χ2, Mann-Whitney U-test and McNemar's tests were performed to compare proportions, means and paired variables, respectively. Clinically significant PCa (CSPCa) was defined as Gleason score ⩾3+4. RESULTS: Fusion biopsy demonstrated exact agreement with SBx risk categories in 64% of AA men. There was no statistically significant difference in the detection of CSPCa between FBx vs SBx (68 vs 62 cases, P=0.36). However, FBx detected 41% fewer cases of clinically insignificant PCa (CIPCa) compared with SBx (FBx 30 vs SBx 51 cases, P=0.0004). The combined FBx/SBx biopsy approach detected significantly more cases of CSPCa (FBx/SBx 80 vs SBx 62 cases, P=0.004) while detecting comparable number of cases of CIPCa (FBx/SBx 45 vs SBx 51 cases, P=0.37) compared with SBx alone. FBx/SBx also detected more CSPCa in patients with a history of prior negative SBx (FBx/SBx 28 vs 19 cases, P=0.003). CONCLUSIONS: FBx when used in combination with SBx detected more cases of CSPCa while not significantly increasing the diagnosis of CIPCa in AA men. Future multicenter studies will be needed to validate ultimately the clinical implications of FBx in AA patients.


Subject(s)
Prostate/pathology , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Black or African American , Aged , Diagnostic Errors , Humans , Image-Guided Biopsy , Magnetic Resonance Imaging , Male , Middle Aged , Prostate/diagnostic imaging , Ultrasonography
7.
Prostate Cancer Prostatic Dis ; 20(2): 179-185, 2017 06.
Article in English | MEDLINE | ID: mdl-28220802

ABSTRACT

BACKGROUND: The Prostate Cancer Prevention Trial Risk Calculator 2.0 (PCPTRC) is a widely used risk-based calculator used to assess a man's risk of prostate cancer (PCa) before biopsy. This risk calculator was created from data of a patient cohort undergoing a 6-core sextant biopsy, and subsequently validated in men undergoing 12-core systematic biopsy (SBx). The accuracy of the PCPTRC has not been studied in patients undergoing magnetic resonance imaging/ultrasound (MRI/US) fusion-guided biopsy (FBx). We sought to assess the performance of the PCPTRC for straitifying PCa risk in a FBx cohort. METHODS: A review of a prospective cohort undergoing MRI and FBx/SBx was conducted. Data from consecutive FBx/SBx were collected between August 2007 and February 2014, and PCPTRC scores using the PCPTRC2.0R-code were calculated. The risk of positive biopsy and high-grade cancer (Gleason ⩾7) on biopsy was calculated and compared with overall and high-grade cancer detection rates (CDRs). Receiver operating characteristic curves were generated and the areas under the curves (AUCs) were compared using DeLong's test. RESULTS: Of 595 men included in the study, PCa was detected in 39% (232) by SBx compared with 48% (287) on combined FBx/SBx biopsy. The PCPTRC AUCs for the CDR were similar (P=0.70) for SBx (0.69) and combined biopsy (0.70). For high-grade disease, AUCs for SBx (0.71) and combined biopsy (0.70) were slightly higher, but were not statistically different (P=0.55). CONCLUSIONS: In an MRI-screened population of men undergoing FBx, PCPTRC continues to represent a practical method of accurately stratifying PCa risk.


Subject(s)
Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Image-Guided Biopsy/methods , Prostate/diagnostic imaging , Prostatic Neoplasms/diagnosis , Aged , Early Detection of Cancer , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Prostate/pathology , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Risk Assessment
8.
Eur J Nucl Med Mol Imaging ; 44(3): 500-508, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27872957

ABSTRACT

BACKGROUND: Z-endoxifen is the most potent of the metabolites of tamoxifen, and has the potential to be more effective than tamoxifen because it bypasses potential drug resistance mechanisms attributable to patient variability in the expression of the hepatic microsomal enzyme CYP2D6. 18F-FES is a positron emission tomography (PET) imaging agent which selectively binds to estrogen receptor alpha (ER-α) and has been used for non-invasive in vivo assessment of ER activity in tumors. This study utilizes 18F-FES PET imaging as a pharmacodynamic biomarker in patients with ER+ tumors treated with Z-endoxifen. METHODS: Fifteen patients were recruited from a parent therapeutic trial of Z-endoxifen and underwent imaging with 18F-FES PET at baseline. Eight had positive lesions on the baseline scan and underwent follow-up imaging with 18F-FES 1-5 days post administration of Z-endoxifen. RESULTS: Statistically significant changes (p = 0.0078) in standard uptake value (SUV)-Max were observed between the baseline and follow-up scans as early as 1 day post drug administration. CONCLUSION: F-FES PET imaging could serve as a pharmacodynamic biomarker for patients treated with ER-directed therapy.


Subject(s)
Breast Neoplasms, Male/diagnostic imaging , Breast Neoplasms/diagnostic imaging , Estradiol/analogs & derivatives , Genital Neoplasms, Female/diagnostic imaging , Positron Emission Tomography Computed Tomography , Radiopharmaceuticals , Adult , Aged , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms, Male/drug therapy , Breast Neoplasms, Male/genetics , Estrogen Antagonists/therapeutic use , Female , Genital Neoplasms, Female/drug therapy , Genital Neoplasms, Female/genetics , Humans , Male , Middle Aged , Receptors, Estrogen/antagonists & inhibitors , Receptors, Estrogen/genetics , Tamoxifen/analogs & derivatives , Tamoxifen/therapeutic use
9.
Clin Radiol ; 70(11): 1165-76, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26231470

ABSTRACT

Prostate cancer is the second most prevalent cancer in men worldwide and its incidence is expected to double by 2030. Multi-parametric magnetic resonance imaging (MRI) incorporating anatomical and functional imaging has now been validated as a means of detecting and characterising prostate tumours and can aid in risk stratification and treatment selection. The European Society of Urogenital Radiology (ESUR) in 2012 established the Prostate Imaging-Reporting and Data System (PI-RADS) guidelines aimed at standardising the acquisition, interpretation and reporting of prostate MRI. Subsequent experience and technical developments have highlighted some limitations, and a joint steering committee formed by the American College of Radiology, ESUR, and the AdMeTech Foundation have recently announced an updated version of the proposals. We summarise the main proposals of PI-RADS version 2, explore the evidence behind the recommendations, and highlight key differences for the benefit of those already familiar with the original.


Subject(s)
Magnetic Resonance Imaging/methods , Prostatic Neoplasms/pathology , Humans , Magnetic Resonance Imaging/standards , Male , Neoplasm Staging/methods , Neoplasm Staging/standards , Practice Guidelines as Topic , Research Design/standards , Sensitivity and Specificity
10.
Eur J Nucl Med Mol Imaging ; 42(12): 1794-800, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26162799

ABSTRACT

PURPOSE: PET/CT with the PSMA ligand is a powerful new method for the early detection of nodal metastases in patients with biochemical relapse. The purpose of this retrospective investigation was to evaluate the volume and dimensions of nodes identified by Glu-urea-Lys-(Ahx)-[(68)Ga(HBED-CC)] ((68)Ga-PSMA-11) in the setting of recurrent prostate cancer. METHODS: All PET/CT images were acquired 60 ± 10 min after intravenous injection of (68)Ga-PSMA-11 (mean dose 176 MBq). In 21 patients with recurrent prostate cancer and rising PSA, 49 PSMA-positive lymph nodes were identified. Using semiautomated lymph node segmentation software, node volume and short-axis and long-axis dimensions were measured and compared with the maximum standardized uptake values (SUVmax). Round nodes greater than or equal to 8 mm were considered positive by morphological criteria alone. The percentage of nodes identified by elevated SUVmax but not by conventional morphological criteria was determined. RESULTS: The mean volume of (68)Ga-PSMA-11-positive nodes was 0.5 ml (range 0.2 - 2.3 ml), and the mean short-axis diameter was 5.8 mm (range 2.4 - 13.3 mm). In 7 patients (33.3 %) with 31 PSMA-positive nodes only 11 (36 %) were morphologically positive based on diameters >8 mm on CT. In the remaining 14 patients (66.7 %), 18 (37 %) of PSMA positive lymph nodes had short-axis diameters <8 mm with a mean short-axis diameter of 5.0 mm (range 2.4 - 7.9 mm). Thus, in this population, (68)Ga-PSMA-11 PET/CT detected nodal recurrence in two-thirds of patients who would have been missed using conventional morphological criteria. CONCLUSION: (68)Ga-PSMA-11 PET/CT is more sensitive than CT based 3D volumetric lymph node evaluation in determining the node status of patients with recurrent prostate cancer, and is a promising method of restaging prostate cancers in this setting.


Subject(s)
Edetic Acid/analogs & derivatives , Imaging, Three-Dimensional , Multimodal Imaging , Oligopeptides , Positron-Emission Tomography , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/pathology , Aged , Gallium Isotopes , Gallium Radioisotopes , Humans , Lymphatic Metastasis , Male , Middle Aged , Prostatic Neoplasms/diagnostic imaging , Radiography , Recurrence , Retrospective Studies
11.
Med Phys ; 42(1): 69-80, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25563248

ABSTRACT

PURPOSE: T2-weighted magnetic resonance imaging (MRI) is commonly used for anatomical visualization in the pelvis area, such as the prostate, with high soft-tissue contrast. MRI can also provide functional information such as diffusion-weighted imaging (DWI) which depicts the molecular diffusion processes in biological tissues. The combination of anatomical and functional imaging techniques is widely used in oncology, e.g., for prostate cancer diagnosis and staging. However, acquisition-specific distortions as well as physiological motion lead to misalignments between T2 and DWI and consequently to a reduced diagnostic value. Image registration algorithms are commonly employed to correct for such misalignment. METHODS: The authors compare the performance of five state-of-the-art nonrigid image registration techniques for accurate image fusion of DWI with T2. RESULTS: Image data of 20 prostate patients with cancerous lesions or cysts were acquired. All registration algorithms were validated using intensity-based as well as landmark-based techniques. CONCLUSIONS: The authors' results show that the "fast elastic image registration" provides most accurate results with a target registration error of 1.07 ± 0.41 mm at minimum execution times of 11 ± 1 s.


Subject(s)
Diffusion Magnetic Resonance Imaging , Image Processing, Computer-Assisted/methods , Movement , Prostate , Humans , Male , Prostatic Neoplasms/diagnosis , Reproducibility of Results
13.
Curr Mol Med ; 13(10): 1568-78, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24206135

ABSTRACT

Many molecular imaging probes have been developed in recent years that hold great promise for both diagnostic and therapeutic functions in urogynecologic disease. Historically, optical probe designs were based on either endogenous or exogenous fluorophores. More recently, organic fluorophore probes have been engineered to target specific tissues and emit fluorescence only upon binding to targets. Several different photochemical mechanisms of activation exist. This review presents a discussion of the history and development of molecular imaging probe designs and provides an overview of successful preclinical and clinical models employing molecular probes for in vivo imaging of urogynecologic cancers.


Subject(s)
Female Urogenital Diseases/diagnosis , Fluorescent Dyes , Male Urogenital Diseases/diagnosis , Molecular Imaging , Molecular Probes , Animals , Female , Female Urogenital Diseases/metabolism , Fluorescence , Humans , Male , Male Urogenital Diseases/metabolism
14.
Clin Oncol (R Coll Radiol) ; 25(8): 451-60, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23722008

ABSTRACT

Prostate cancer is currently the most common solid organ cancer type among men in the Western world. Currently, all decision-making algorithms and nomograms rely on demographics, clinicopathological data and symptoms. Such an approach can easily miss significant cancers while detecting many insignificant cancers. In this review, novel functional and molecular imaging techniques used in the diagnosis and staging of localised prostate cancer and their effect on treatment decisions are discussed.


Subject(s)
Molecular Imaging/methods , Prostatic Neoplasms/diagnosis , Humans , Male , Neoplasm Staging , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Radiography
15.
Curr Med Chem ; 19(28): 4759-66, 2012.
Article in English | MEDLINE | ID: mdl-22873662

ABSTRACT

Epidermal growth factor (EGF) receptors are commonly expressed on the cell membrane of cancer cells and activity of these receptors results in accelerated cell growth and carcinogenesis. A variety of targeted molecules have been developed to block ligand binding and/or inhibit the function of these receptor tyrosine kinases, and several have proven therapeutic benefits. Along with the advent of new therapeutic agents comes a need for non-invasive tools to diagnose, characterize, and monitor tumor responsiveness to therapy. Imaging EGF receptors with radionuclides has been performed for decades. However, recently this area has advanced considerably with the development of EGF receptor-targeted optical imaging probes. Herein, we review recent advances in molecular imaging of the EGF receptor family, focusing specifically on optical imaging. Such agents provide the opportunity for earlier diagnosis, improved tumor characterization, and the ability to measure and monitor tumor responsiveness to anti-EGF receptor treatment strategies.


Subject(s)
ErbB Receptors/metabolism , Neoplasms/diagnosis , Optical Imaging , Animals , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/immunology , ErbB Receptors/chemistry , Fluorescent Dyes/chemistry , Humans , Neoplasms/metabolism , Radiopharmaceuticals/chemistry , Receptor, ErbB-2/chemistry , Receptor, ErbB-2/metabolism
16.
Nanotechnology ; 21(17): 175704, 2010 Apr 30.
Article in English | MEDLINE | ID: mdl-20368682

ABSTRACT

Multi-modality imaging probes combine the advantages of individual imaging techniques to yield highly detailed anatomic and molecular information in living organisms. Herein, we report the synthesis and characterization of a dual-modality nanoprobe that couples the magnetic properties of ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) with the near infrared fluorescence of Cy5.5. The fluorophore is encapsulated in a biocompatible shell of silica surrounding the iron oxide core for a final diameter of approximately 17 nm. This silica-coated iron oxide nanoparticle (SCION) has been analyzed by transmission electron microscopy, dynamic light scattering, and superconducting quantum interference device (SQUID). The particle demonstrates a strong negative surface charge and maintains colloidal stability in the physiological pH range. Magnetic hysteresis analysis confirms superparamagnetic properties that could be manipulated for thermotherapy. The viability of primary human monocytes, T cells, and B cells incubated with the particle has been examined in vitro. In vivo analysis of agent leakage into subcutaneous A431 tumors in mice was also conducted. This particle has been designed for diagnostic application with magnetic resonance and fluorescence imaging, and has future potential to serve as a heat-sensitive targeted drug delivery platform.


Subject(s)
Diagnostic Imaging/methods , Ferric Compounds/chemistry , Magnetics , Metal Nanoparticles/chemistry , Microscopy, Fluorescence/methods , Molecular Probe Techniques , Animals , Carbocyanines/metabolism , Cell Survival , Cells, Cultured , Drug Delivery Systems , Humans , Leukocytes, Mononuclear/metabolism , Mice , Propylamines , Silanes
17.
Int J Comput Assist Radiol Surg ; 4(5): 457-62, 2009 Sep.
Article in English | MEDLINE | ID: mdl-20033528

ABSTRACT

PURPOSE: The purpose of this study was to evaluate the diagnostic value and tumor-vascular display properties (microcirculation) of two different functional MRI post-processing and display (color and gray-scale display) techniques used in oncology. MATERIALS AND METHODS: The study protocol was approved by the IRB and written informed consent was obtained from all patients. 38 dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) data sets of patients with malignant pleural-mesothelioma were acquired and post-processed. DCE-MRI was performed at 1.5 tesla with a T1-weighted 2D gradient-echo-sequence (TR 7.0 ms, TE 3.9 ms, 15 axial slices, 22 sequential repetitions), prior and during chemotherapy. Subtracting first image of contrast-enhanced-dynamic series from the last, produced gray-scale images. Color images were produced using a pharmacokinetic two-compartment model. Eight raters, blinded to diagnosis, by visual assessment of post-processed images evaluated both diagnostic quality of the images and vasculature of the tumor using a rating scale ranging from -5 to +5. The scores for vasculature were assessed by correlating with the maximum amplitude of the total-tumor-ROI for accuracy. RESULTS: Color coded images were rated as significantly higher in diagnostic quality and tumor vascular score than gray-scale images (p < 0.001, 0.005). ROI signal amplitude analysis and vascular ratings on color coded images were better correlated compared to gray-scale images rating (p < 0.05). CONCLUSION: Color coded images were shown to have higher diagnostic quality and accuracy with respect to tumor vasculature in DCE-MRI, therefore their implementation in clinical assessment and follow-up should be considered for wider application.


Subject(s)
Diagnosis, Computer-Assisted , Image Enhancement , Magnetic Resonance Imaging , Mesothelioma/diagnosis , Pleural Neoplasms/diagnosis , Aged , Cohort Studies , Contrast Media , Female , Gadolinium DTPA , Humans , Male , Mesothelioma/therapy , Middle Aged , Pleural Neoplasms/therapy , Predictive Value of Tests , Reproducibility of Results
18.
Exp Oncol ; 31(2): 106-14, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19550401

ABSTRACT

AIM: To evaluate the feasibility of fusion of morphologic and functional imaging modalities to facilitate treatment planning, probe placement, probe re-positioning, and early detection of residual disease following radiofrequency ablation (RFA) of cancer. METHODS: Multi-modality datasets were separately acquired that included functional (FDG-PET and DCE-MRI) and standard morphologic studies (CT and MRI). Different combinations of imaging modalities were registered and fused prior to, during, and following percutaneous image-guided tumor ablation with radiofrequency. Different algorithms and visualization tools were evaluated for both intra-modality and inter-modality image registration using the software MIPAV (Medical Image Processing, Analysis and Visualization). Semi-automated and automated registration algorithms were used on a standard PC workstation: 1) landmark-based least-squares rigid registration, 2) landmark-based thin-plate spline elastic registration, and 3) automatic voxel-similarity, affine registration. RESULTS: Intra- and inter-modality image fusion were successfully performed prior to, during and after RFA procedures. Fusion of morphologic and functional images provided a useful view of the spatial relationship of lesion structure and functional significance. Fused axial images and segmented three-dimensional surface models were used for treatment planning and post-RFA evaluation, to assess potential for optimizing needle placement during procedures. CONCLUSION: Fusion of morphologic and functional images is feasible before, during and after radiofrequency ablation of tumors in abdominal organs. For routine use, the semi-automated registration algorithms may be most practical. Image fusion may facilitate interventional procedures like RFA and should be further evaluated.


Subject(s)
Catheter Ablation , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging , Neoplasms/therapy , Positron-Emission Tomography , Therapy, Computer-Assisted/methods , Algorithms , Humans , Software , Tomography, X-Ray Computed
19.
Curr Radiopharm ; 2(1): 9-17, 2009 Jan.
Article in English | MEDLINE | ID: mdl-20047017

ABSTRACT

Better tumor markers are needed for early diagnosis and staging of prostate cancer, and for monitoring therapeutic response than the currently used prostate specific antigen (PSA). Prostate specific membrane antigen (PSMA) is highly expressed on the surface of prostatic epithelial cells making it a good target for prostate cancer. In this study, mAb 3C6, specific for the extracellular epitope of PSMA, was evaluated both in vitro and in vivo for PSMA-targeting. Immunoreactivity and specificity of mAb 3C6 was evaluated by flow cytometry using prostate cell lines expressing PSMA such as LNCaP and 22Rv1 and a cell line, DU145, that expresses very little PSMA. 3C6 was conjugated with the acyclic CHX-A" DTPA chelate, radiolabeled with (111)In, and its in vitro and in vivo properties were assessed. The biodistribution of the radioimmunoconjugate evaluated in athymic mice bearing xenografts of three human prostate carcinoma cell lines shows high uptake after 72 hr in LNCaP tumors (%ID/g 22.93 +/- 6.32) and 22Rv1 (%ID/g 10.44 +/- 2.32) in contrast to low uptake by the DU145 tumors (%ID/g 4.27 +/- 0.37). Planar gamma-scintigraphic images obtained for xenografted tumor bearing mice demonstrated targeting for PSMA positive tumors suggesting possible applications in imaging and for targeted radiation therapy.

20.
Nanotechnology ; 19(33): 335601, 2008 Aug 20.
Article in English | MEDLINE | ID: mdl-19701448

ABSTRACT

Ultra-small superparamagnetic iron oxide nanoparticles (SPIOs) were synthesized by co-precipitation of iron chloride salts with ammonia and then encapsulated with thin (~2nm) layers of silica. The particles have been characterized for size, diffraction pattern, surface charge, and magnetic properties. This rapid and economical synthesis has a number of industrial applications; however, the silica-coated particles have been optimized for use in medical applications as MR contrast agents, biosensors, DNA capturing, bioseparation and enzyme immobilization.

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