Molecular Imaging-Guided Theranostics and Personalized Medicine

143 Pages·2013·27.03 MB·English

BioMed Research International
Molecular Imaging-Guided Theranostics
and Personalized Medicine
Guest Editors: David J. Yang, Fong Y. Tsai, Tomio Inoue, Mei-Hsiu Liao,
Fan-Lin Kong, and Shaoli Song
Molecular Imaging-Guided Theranostics and
Personalized Medicine
BioMed Research International
Molecular Imaging-Guided Theranostics and
Personalized Medicine
Guest Editors: David J. Yang, Fong Y. Tsai, Tomio Inoue,
Mei-Hsiu Liao, Fan-Lin Kong, and Shaoli Song
Copyright © 2013 Hindawi Publishing Corporation. All rights reserved.
Tis is a special issue published in “BioMed Research International.” All articles are open access articles distributed under the Creative
Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original
work is properly cited.
Contents
Molecular Imaging-GuidedTeranostics and Personalized Medicine, David J. Yang, Fong Y. Tsai,
Tomio Inoue, Mei-Hsiu Liao, Fan-Lin Kong, and Shaoli Song
Volume 2013, Article ID 859453, 2 pages
In Vivo Evidence of Increased nNOS Activity in Acute MPTP Neurotoxicity: A Functional
Pharmacological MRI Study, Tiing Yee Siow, Chiao-Chi V. Chen, Nina Wan, Kai-Ping N. Chow,
and Chen Chang
Volume 2013, Article ID 964034, 7 pages
Molecular Imaging of Nonsmall Cell Lung Carcinomas Expressing Active Mutant EGFR Kinase Using
124
PET with [ I]-Morpholino-IPQA, Skye Hsin-Hsien Yeh, Chien-Feng Lin, Fan-Lin Kong, Hsin-Ell Wang,
Ya-Ju Hsieh, Juri G. Gelovani, and Ren-Shyan Liu
Volume 2013, Article ID 549359, 10 pages
18
Synthesis and Biological Evaluation of O-[3- F-fuoropropyl]-𝛼-methyl Tyrosine in
Mesothelioma-Bearing Rodents, I-Hong Shih, Fan-Lin Kong, Mohammad S. Ali, Yinhan Zhang,
Dong-Fang Yu, Xudong Duan, and David J. Yang
Volume 2013, Article ID 460619, 9 pages
Afnity Labeling of Membrane Receptors Using Tissue-Penetrating Radiations, Franklin C. Wong,
John Boja, Beng Ho, Michael J. Kuhar, and Dean F. Wong
Volume 2013, Article ID 503095, 7 pages
177 90
Kidney Dosimetry in Lu and Y Peptide Receptor RadionuclideTerapy: Infuence of Image
Timing, Time-Activity Integration Method, and Risk Factors, F. Guerriero, M. E. Ferrari, F. Botta,
F. Fioroni, E. Grassi, A. Versari, A. Sarnelli, M. Pacilio, E. Amato, L. Strigari, L. Bodei, G. Paganelli, M. Iori,
G. Pedroli, and M. Cremonesi
Volume 2013, Article ID 935351, 12 pages
Te Adjunctive Digital Breast Tomosynthesis in Diagnosis of Breast Cancer, Tsung-Lung Yang,
Huei-Lung Liang, Chen-Pin Chou, Jer-Shyung Huang, and Huay-Ben Pan
Volume 2013, Article ID 597253, 7 pages
Managing Lymphoma with Non-FDG Radiotracers: Current Clinical and Preclinical Applications,
Fan-Lin Kong, Richard J. Ford, and David J. Yang
Volume 2013, Article ID 626910, 12 pages
Clinical Application of Magnetic Resonance Imaging in Management of Breast Cancer Patients
Receiving Neoadjuvant Chemotherapy, Jeon-Hor Chen and Min-Ying Su
Volume 2013, Article ID 348167, 14 pages
Advanced MR Imaging of Gliomas: An Update, Hung-Wen Kao, Shih-Wei Chiang, Hsiao-Wen Chung,
Fong Y. Tsai, and Cheng-Yu Chen
Volume 2013, Article ID 970586, 14 pages
18
Te Potential Roles of F-FDG-PET in Management of Acute Stroke Patients, Adomas Bunevicius,
Hong Yuan, and Weili Lin
Volume 2013, Article ID 634598, 14 pages
Toward the Era of a One-Stop Imaging Service Using an Angiography Suite for Neurovascular
Disorders, Sheng-Che Hung, Chung-Jung Lin, Wan-Yuo Guo, Feng-Chi Chang, Chao-Bao Luo,
Michael Mu-Huo Teng, and Cheng-Yen Chang
Volume 2013, Article ID 873614, 7 pages
Pharmacodynamic Analysis of Magnetic Resonance Imaging-Monitored Focused Ultrasound-Induced
Blood-Brain Barrier Opening for Drug Delivery to Brain Tumors, Po-Chun Chu, Wen-Yen Chai,
Han-Yi Hsieh, Jiun-Jie Wang, Shiaw-Pyng Wey, Chiung-Yin Huang, Kuo-Chen Wei, and Hao-Li Liu
Volume 2013, Article ID 627496, 13 pages
Signifcance of Coronary Calcifcation for Prediction of Coronary Artery Disease and Cardiac Events
Based on 64-Slice Coronary Computed Tomography Angiography, Yuan-Chang Liu, Zhonghua Sun,
Pei-Kwei Tsay, Tifany Chan, I-Chang Hsieh, Chun-Chi Chen, Ming-Shien Wen, and Yung-Liang Wan
Volume 2013, Article ID 472347, 9 pages
Hindawi Publishing Corporation
BioMed Research International
Volume 2013, Article ID 859453, 2 pages
http://dx.doi.org/10.1155/2013/859453
Editorial
Molecular Imaging-Guided Theranostics
and Personalized Medicine
1 2,3 4 5
David J. Yang, Fong Y. Tsai, Tomio Inoue, Mei-Hsiu Liao,
6 7
Fan-Lin Kong, and Shaoli Song
1
Diagnostic Imaging, Te University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
2
Taipei Medical University, Taipei 11031, Taiwan
3
University of California at Irvine, Orange, CA 92868, USA
4
Department of Radiology, Yokohama City University School of Medicine, 3-9 Fukuura Kanazawa-ku, Yokohama 236-0004, Japan
5
Radiopharmaceuticals Production and Marketing Center, Institute of Nuclear Energy Research, Atomic Energy Council,
Taoyuan 32546, Taiwan
6
Department of Cancer Systems Imaging, Te University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
7
Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
Correspondence should be addressed to David J. Yang;
2 BioMed Research International
reported that the brain tumor conditions on the distribution
and dynamics of small molecule leakage into targeted regions
of the brain could be infuenced by focused ultrasound
(FUS)-BBB opening. Teir fndings indicated that FUS-
BBB opening might have the most signifcant permeability-
enhancing efect on tumor peripheral. Teir report provides
useful information toward designing an optimized FUS-BBB
opening strategy to deliver small-molecule therapeutic agents
into brain tumors.
MRI has been proven to be a valuable tool to pro-
vide important information facilitating individualized image-
guided treatment and personalized management for cancers.
J.-H. Chen and M.-Y. Su reviewed the use of diferent
MR imagingmethods, including dynamic contrast-enhanced
MRI proton MR spectroscopy, and difusion-weighted MRI,
to monitor and evaluate the treatment response. Tey also
described how the changes of parameters measured at an
early time afer initiation of a drug regimen could predict fnal
treatment outcome. H.-W. Kao et al. also reviewed advanced
MR imaging techniques including cellularity, invasiveness,
mitotic activity, angiogenesis, and necrosis in gliomas.Molec-
ular imaging with MRI also permits mapping and measuring
the rate of physiological, biochemical, and molecular process
with the use of appropriate kinetic models. For instance,
T. Y. Siow et al. described their MRI fndings with increased
nNOS activity in brain cortex and striatum afer 1-methyl-4-
phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. Tey
concluded that the transient changes in hyperperfusion state
in cerebral blood fow in the cortex and striatummight be an
early indicator of neuronal infammation.
T.-L. Yang et al. compared the diagnostic performance
of digital breast tomosynthesis (DBT) and digital mam-
mography (DM) for breast cancers. Tey concluded that
adjunctive DBT provided exquisite information for mass
lesion, focal asymmetry, and/or architecture distortion which
could improve the diagnostic performance inmammography.
Y.-C. Liu et al. reported the validation of the clinical signif-
cance of coronary artery calcium score (CACS) in predicting
coronary artery disease (CAD) and cardiac events using a 64-
slice coronary CT angiography. Tey concluded that CACS
was signifcantly correlated with CAD and cardiac events.
Te emergence of fat-detector X-ray angiography in
conjunction with contrast medium injection and specialized
reconstruction algorithms can provide not only high-quality
and high-resolution CT-like images but also functional infor-
mation. Tis improvement in imaging technology allows
quantitative assessment of intracranial hemodynamics and
subsequently in the same imaging session. S.-C. Hung et al.
described the recent developments in the feld of fat-detector
imaging and shared their experience of applying this technol-
ogy in neurovascular disorders such as acute ischemic stroke,
cerebral aneurysm, and steno occlusive carotid diseases.
David J. Yang
Fong Y. Tsai
Tomio Inoue
Mei-Hsiu Liao
Fan-Lin Kong
Shaoli Song
Hindawi Publishing Corporation
BioMed Research International
Volume 2013, Article ID 964034, 7 pages
http://dx.doi.org/10.1155/2013/964034
Research Article
In Vivo Evidence of Increased nNOS Activity in Acute MPTP
Neurotoxicity: A Functional Pharmacological MRI Study
1,2 1 3 4 1
Tiing Yee Siow, Chiao-Chi V. Chen, NinaWan, Kai-Ping N. Chow, and Chen Chang
1
Institute of Biomedical Sciences, Academia Sinica, 128 Section 2, Academia Road, Nankang, Taipei 11529, Taiwan
2
Department of Medical Imaging and Intervention, Chang-Gung Memorial Hospital,
Chang-Gung University College of Medicine, Taoyuan 33302, Taiwan
3
School of Nursing, Queen’s University, Kingston, ON, Canada K7L 3N6
4
Department of Microbiology and Immunology, Chang-Gung University, Taoyuan 33302, Taiwan
Correspondence should be addressed to Chen Chang;
2 BioMed Research International
(nNOS), which is a calmodulin-dependent enzyme [16]. Te volume and ventilation rate. An intravenous (i.v.) injection
subsequently produced NO combines with superoxide to of a muscle relaxant, gallamine (Sigma), was used to prevent
form the free radical peroxynitrite [17], which in turn degen- spontaneous ventilation and movement during the image-
erates into a more noxious hydroxyl radical to cause cell acquisition period. Te initial dose of gallamine was 12mgs
injury. Nevertheless, NO activity is difcult to assess in vivo and the maintenance dosage was 6mg/h. Body temperature
due to its extremely short biological half-life of only a few was detected by an optical fber thermoprobe (Model SFF-5,
seconds [18]. In vivo evidence of NO involvement in MPTP Luxtron, Santa Clara, CA, USA) connected to a Fluoroptic
neurotoxicity remains scarce. thermometer (Model 790, Luxtron) and was maintained at
∘
As well as playing a part in neuroinfammation, NO is 37 C by a ceramic heater (Model TH-8105, Tashin, Taipei,
known to play a pivotal role in the regulation of vascular tone Taiwan) throughout the MRI measurements.
[19, 20].Te central efect of NO in hemodynamic homeosta- Te rats were divided into three groups, with six rats in
sis provides a rationale for the present study, which examined each group. In the frst group, the rats received a single, i.v.
the role of NO in the MPTP-induced neurotoxic cascade by injection of MPTP (15mg/kg, Sigma), while the age-matched
monitoring alterations in CBF. control group received an i.v. injection of normal saline. Te
Over the past few decades, magnetic resonance imaging third group of rats received a single dose of 7-NI (50mg/kg
(MRI) has evolved into a powerful imaging modality that i.p., Sigma) 30min prior to the i.v. administration of 15mg/kg
ofers functional imaging in addition to anatomical infor- MPTP. As shown previously [27], maximal NOS inhibition
mation. Flow-sensitive alternating inversion recovery (FAIR) in the rat brain is manifested within 30 min following the
[21], a commonly used magnetic-resonance-based perfusion injection of 7-NI i.p.
imaging technique, utilizes tissue water as an endogenous
contrast agent to obtain tissue perfusion information. In 2.2. MRI Protocols. All magnetic resonance experiments
addition to FAIR, functional imaging modalities such as were performed on a 4.7-T Biospec 47/40 spectrometer with
difusion-weighted imaging (DWI) and magnetic resonance an active shielding gradient (5.6G/cm in 500 𝜇s). A 20 cm
spectroscopy (MRS) could provide useful information on birdcage coil was used for radiofrequency (RF) excitation,
cytotoxicity and metabolic changes. Te noninvasiveness of and a 2 cmdiameter surface coil was used for signal reception.
these techniques enables repeated in vivo measurements with Conventional DWI was employed using a pulsed-
high temporal and spatial resolutions. gradient spin-echo difusion method, with a repetition time
Combining these MRI techniques with pharmacological (TR) of 2000ms, an echo time (TE) of 59ms, a gradient pulse
inquires, termed pharmacological MRI (phMRI) [22–24], duration of 20ms, a time interval between difusion gradient
has provided a platform for investigating drug efects in 2
pulses of 27ms, and a 𝑏 value of 1300 s/mm . Images were
vivo. Te present study used phMRI to investigate the acute
obtained using a 5 cm feld of view (FOV), a slice thickness of
efects ofMPTP on the rodent central nervous system (CNS).
2mm, a 256×128matrix size that was zero flled to 256×256,
FAIR, DWI, and in vivo localized proton magnetic resonance
and a total imaging time of 4min 17 s.Te difusion-sensitive
1
spectroscopy ( H-MRS) were used to, respectively, assess
gradients were applied in the read (𝑥) direction before and
MPTP-induced hemodynamic perturbations, cytotoxicity,
afer the refocusing pulse. Hermite-shaped RF pulses with
and metabolic changes. To further clarify the role of NO in
durations of 3 and 1.86ms were used for the excitation and
MPTP toxicity, a selective nNOS inhibitor, 7-nitroindazole (7-
refocusing pulses, respectively.
NI) [25], was administered intraperitoneally (i.p.) to experi-
Te FAIR experiment was implemented with inversion
mental animals prior to an MPTP challenge.
recovery fast spin-echo (IR-FSE) sequences with and without
a slice-selective gradient during an inversion pulse. Slice-
2. Materials and Methods
selective IR-FSE (ssIR-FSE) and non-slice-selective IR-FSE
(nsIR-FSE) images were collected using a TR of 3 s, a TE of
2.1. Animal Preparations. All experimental procedures were
20ms, and an efective TE of 50ms with an echo train length
approved by the Institute of Animal Care and Utiliza-
of 4, a slice thickness of 2mm, an FOV of 4 cm, an inversion
tion Committee at Academia Sinica, Taipei, Taiwan. Male
time (TI) of 1.5 s, and a matrix size of 256 × 128. A slab
Sprague-Dawley rats (4-5 months old) weighing 450–550 g
thickness of 5mm was inverted for the ssIR-FSE images and
were anesthetized i.p. with amixture of urethane (800mg/kg;
a hyperbolic secant pulse was used for inversion with a pulse
Sigma, MO, USA) in normal saline and 𝛼-chloralose
(40mg/kg, Sigma) in polyethylene glycol (Merck, Darmstadt, length of 8ms. Te 𝑇1 was measured from nsIR-FSE with TI
values of 0.5, 0.9, 1.1, 1.3, 1.5, and 1.9 s.
Germany). Each rat was placed in the prone position and
A point-resolved spectroscopy (PRESS) sequence was
ftted with a custom-designed head-holder. Te rats were set
used for localized spectroscopy with the following parame-
up as described previously [26]. Briefy, one femoral vein was
3
cannulated with PE-50 tubing for drug/test solution admin- ters: 5×5×5mm voxel located at the striatal region, spectral
istration, and an endotracheal tube (PE-280) was inserted width = 4000Hz, TR = 2 s, TE = 136ms, number of average =
for artifcial ventilation with an animal ventilator (Model 256, and total scanning time = 8min 32 s. Water suppression
683, Harvard Instruments, South Natick, MA, USA). Te was achieved by chemical-shif-selective saturation, whereby
expiratory CO2 concentration, which was monitored with three consecutive Hermite-shaped RF pulses, each of 15ms
the aid of a capnograph (Normocap 200, Datex, Helsinki, duration, are applied followed by spoiling gradients pre-
Finland), was maintained at 3.5-4.5% by adjusting the tidal ceding the PRESS sequence. Spectral assignments of the