Molecular Imaging of Neuropsychiatry and Neuro-oncology

Ya-Fang Chang1, Chun-Kai Fang1,2, Hui-Yen Chuang1, Jeng-Jong Hwang1

1Department of Biomedical Imaging and Radiological Sciences, National Yang-

Ming University, Taipei, Taiwan2Department of Psychiatry, Mackay Memorial Hospital, Taipei, Taiwan

Running title: Molecular imaging of brain diseases

Corresponding author:

Jeng-Jong Hwang, Ph.D., Professor, Department of Biomedical Imaging and

Radiological Sciences, National Yang-Ming University

No. 155, Sec. 2, Li-Nong St, Bei-tou, Taipei 112, TAIWAN

Tel: +886-2-28267064; Fax: +886-2-28201095; Email: jjhwang@ym.edu.tw

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Abstract

Both neuropsychiatric disorders and malignancies of central nervous system

(CNS) represent a significant health burden and life-threatening diseases

worldwide. Radiotracer-based neuroimaging is an attractive tool that permits

the in vivo detection and characterization of metabolic and molecular processes

which are fundamental elements for brain function, and improve the

theranostics of brain diseases and disorders. In this review, we outlined the

newly development of molecular imaging probes for dopamine and serotonin

systems in neuropsychiatry and boron neutron capture therapy (BNCT) for brain

tumors in neuro-oncology with positron emission tomography (PET) and single-

photon emission computed tomography (SPECT).

Keywords: Boron neutron capture therapy, Dopamine, Molecular imaging, Positron

emission tomography, Serotonin, Single-photon emission computed tomography

2

Molecular imaging is definite as the in vivo characterization and

measurement of biologic processes at the cellular and molecular levels [1].

The progress of both neuropsychiatry and neuro-oncology are tremendous in the

past decade. This review will introduce the innovation and application of

molecular imaging in the research and clinical practice for brain diseases and

disorders.

1. Molecular imaging through dopamine system for neuropsychiatry

Dopamine, one of the catecholamine neurotransmitters in the CNS, is

synthesized from amino acid tyrosine by the catalysis of tyrosine hydroxylase

(TH) to L-DOPA, and subsequent decarboxylation by aromatic amino acid

decarboxylase (AADC) to dopamine [2]. Dopaminergic neurons release dopamine

into the synapse, where it signals to post-synaptic neurons through receptors.

Dopamine is then uptake back into the pre-synaptic neuron through the dopamine

transporter (DAT) to regulate its concentration in the extracellular space.

Dopamine system plays an essential role in the states of consciousness,

affective function, and movement. Its disturbance has been implicated in many

neurological and neuropsychiatric disorders, such as schizophrenia,

Parkinson’s disease, mood disorder, and substance dependence [3-6].

1.1 Imaging of dopamine synthesis

An alteration of dopaminergic transmission is of interest to the research

of schizophrenia and Parkinson’s disease. Radiolabelled tyrosine or dopamine

precursor DOPA has been used to evaluate dopamine synthesis. Wiese et al.

reported a compromised precursor transport of 11C-tyrosine in patients with

schizophrenia, suggesting that disturbance of tyrosine utilization as a

possible cause of schizophrenia [7, 8]. However, 11C-tyrosine would be

ineffective in assessing dopamine synthesis because tyrosine is predominantly

used for protein synthesis [9]. [18F] uoro-DOPAfl (18F-DOPA) is the rst imagingfi

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agent developed for the dopamine system [10] and its clinical use in the

diagnosis and evaluation of the progression of Parkinson's Disease and

assessment of novel treatments is well described. This radiotracer enters the

brain via an amino acid transporter and is decarboxylated by AADC to [18F]-

fluorodopamine [11, 12]. PET imaging revealed a preferential reduction of 18F-

DOPA uptake in the putamen compared with the caudate in the early stage of

Parkinson’s disease [13, 14], and progressive loss of 18F-DOPA uptake can be

observed and quantified over time [15-17]. A pilot clinical study using 18F-

DOPA to demonstrate the efficacy of ropinirole and levodopa on Parkinson’s

disease was also assessed recently [18-20]. Scanning using 18F-DOPA has also

been used in patients with schizophrenia and showed a higher uptake of 18F-

DOPA in the striatum of the patient, indicating enhanced presynaptic

dopaminergic activity in schizophrenia [21-23].

Although 18F-DOPA provides an in vivo marker of the functional integrity

of dopamine terminals, some concerns are addressed as the following: first,18F-DOPA imaging is likely to result in underestimation of the degree of

nigrostriatal damage in Parkinsonian patients because of the compensatory up-

regulation of AADC activity in the residual surviving cells [24, 25]; second,

the metabolite of 18F-DOPA via the ubiquitination of catechol-O-

methyltransferase (COMT) raises background signal in the PET image,

diminishing image contrast and complicating analysis [26, 27]; third, the

first and rate-limiting enzyme for dopamine synthesis is TH not AADC, so this

radiotracer cannot be used to measure dopamine synthesis directly [14, 28].

Despite of these limitations, 18F-DOPA is still a widely-used

radiophamaceutical for clinical examinations of psychiatric disorders

currently, except few clinical studies [21-23, 29].

Another AADC-targeting radiotracer, 6-[18F]fluoro-m-tyrosine (18F-FMT),

offers advantages over 18F-DOPA because it has higher affinity for AADC than18F-DOPA and is not a substrate for COMT [30]. PET studies in rhesus monkeys

demonstrated that 18F-FMT is a promising imaging agent to assess dopamine

synthesis [31]. The rst fi PET study comparing FMT with FDOPA in human subjects

found that 18F-FMT better re ected clinical fl symptoms of Parkinson’s disease

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than 18F-DOPA [32].

1.2 Imaging of dopamine receptors

The G protein-coupled dopamine receptor system is by far the most studied

neurotransmitter receptor system of the brain due to the availability of

excellent radiotracers for the dopamine receptors [33]. Postsynaptic dopamine

receptors can be divided into D1-like (D1 and D5 receptors) and D2-like (D2,

D3, and D4 receptors) families, but most attention has been focused on D1and

D2 receptors. 11C-raclopride is the most used PET tracer to visualize striatal

D2 dopamine receptors in clinic and preclinical studies, and is also the gold

standard to evaluate the receptor occupancy and the lease of endogenous

dapomine of patients [34, 35].

The up-regulation of postsynaptic dopamine D2 receptor is noted in the

patients with idiopathic Parkinson’s disease [36, 37]. With the progression of

disease, D2 receptor activity returns to normal or even falls below the normal

value [37]. Theoretically, under conditions of enhanced synaptic-dopamine

release (e.g. following an amphetamine challenge) the increased occupancy of

dopamine D2 receptors by dopamine will result in fewer receptors being

available to bind to 11C-raclopride and, hence, the binding of this

radiotracer should decrease. Indeed, it has proved possible to observe this

effect in the human brain. Some literatures also reported the effect of

antipsychotics on schizophrenic patients by PET with 11C-raclopride [38-41].

In additional, 11C-raclopride has been used to understand the role of dopamine

system in attention-deficit/hyperactivity disorder (ADHD) [42, 43]. 11C-

raclopride is an appropriate probe to explore the mechanism and pathological

changes of dapomine system in cocaine, amphetamine or ketamine addiction [44-

46].

1.3 Imaging of dopamine transporter

DAT is located on the presynaptic dopamine nerve terminals and facilitate

the reuptake of the released dopamine into the presynaptic cell. DAT is also

considered as a marker for the functional integrity of dopamine neurons, and

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has been of interest in relation to Parkinson’s disease. In addition to

radiolabelled tyrosine or dopamine precursor, radiolabelled nomifensine and

substituted analogs of cocaine, such as 11C-nomifensine, 11C-cocaine, 11C-

methyl-phenidate, have been used to investigate the status of the presynaptic

dopamine neuron. PET studies have demonstrated a reduced uptake of these

tracers that correlated with the decrease of 18F-DOPA uptake in patients with

Parkinson’s disease [37]. The SPECT tracer, 123I--CIT, gives the high

striatal:cerebellar uptake ratio, but the clinical applications is limited due

to the non-specific binding to noradrenaline and serotonin transporters and

slow equilibrium throughout the brain after injection [47, 48]. In comparison

with 123I--CIT, 123I-FP-CIT enables a diagnostic scan to be performed within 1-

3 hours after injection although the striatal:cerebellar uptake ratios are

lower and time dependent [49, 50]. Other SPECT tracer, 99mTc-TRODAT, is the

rstfi 99mTc-labeled imaging agent to show speci c binding to DAT in thefi striatum

of the human brain [51]. It has been demonstrated for the diagnosis of DAT

de ciency in fi Parkinson’s disease successfully [51, 52] and for the evaluation

of DAT availability in patients with schizophrenia recently [53, 54]. The

development of a 99mTc-based agent bypasses the need for cyclotron-produced

radionuclides, which will be of benefit for routine clinical studies. However,

the uptake of these PET/SPECT tracers may underestimate dopamine terminal

reserve due to the up-regulation in DA turnover in patients with early stage

of Parkinson’s disease [54, 56]. 99mTc-TRODAT-1 SPECT is also suggested to

provide a reliable alternative to 18F-FDOPA PET in the evaluation of clinical

patients with Parkinson’s disease [57]. In vivo imaging of DAT has also been

used for the assessment of the long term effect of drug treatment on

Parkinson’s disease by measuring DAT occupancy [56-58].

Other literatures focused on drug abuse, where a relationship of the time

course of the DAT blockade to cocaine abuse was found and a long-acting DAT

inhibitor was postulated for antagonizing the pleasurable and additive effect

of this drug [59]. Our preclinical studies showed that the in vivo binding

of 99mTc-TRODAT-1 could clearly demonstrate the change of DAT level after the

treatment of dopaminergic drugs, including N-methyl-2b-carbomethoxy-3b-

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(4fluorophenyl)tropane (CFT), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

(MPTP), l-DOPA and methylphenidate, using ICR mice [60]. Some studies used99mTc-TRODAT with SPECT to assess the changes of dopamine system among human

substance abusers [61, 62].

2. Molecular imaging through serotonin (5-HT) system in neuropsychiatry

Similar to the synthesis of dopamine, tryptophan is converted to 5-

hydroxytryptophan (HTP) via tryptophan hydroxylase (TPH), a limiting enzyme

for 5-HT synthesis, and further metabolized to serotonin by AADC. Alterations

of 5-HT transmission have been implicated in many neurologic and psychiatric

disorders, such as depression, compulsive disorders, Alzheimer’s and

Parkinson’s disease and schizophrenia. However, only few PET/SPECT

radiotracers are applied in clinical practice due to high lipophilicity and/or

high nonspecific binding to other neurotransmitter transporters [63, 64].

2.1 Imaging of 5-HT synthesis11C-Methyl-L-tryptophan (11C-AMT) and 11C-5-hydroxy-L-tryptophan (11C-HTP)

have been promoted as PET tracers for the measurement of 5-HT synthesis [63-

68]. 11C-AMT, an analogue of tryptophan, has been used to index the TPH

activity regarding to antidepressant action. In the present report, 11C-AMT

was applied to study the initial 24 days of an antidepressant treatment in

patients with current major depressive episode and the PET imaging showed a

significant increase of 11C-AMT uptake in the prefrontal cortex, an area

associated to depressive symptoms, indicating that the treatment produces a

greater increase of the metabolism of serotonin [69]. 11C-AMT can be also

metabolized through the kynurenine pathway, thus providing false signals in

PET data [70, 71]. Use of radiolabelled 5-HT precursor, 11C-HTP that will

undergo the same conversions as 5-HTP by ADCC can prevent the conversion to

kynurenine. Eriksson et al. demonstrated a negative correlation between 11C-

HTP trapping and the severity of mood symptoms in women with premenstrual

dysphoria and 11C-HTP may be useful for assessing the therapeutic efficacy of

antidepressants [72]. To the best of our knowledge, there are only few

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published reports on 11C-HTP for imaging 5-HT synthesis because the

difficulties in radiolabelling have invalidated its widespread applications.

However, the feasibility of combined 11C-AMT/11C-HTP imaging may provide a

better understanding of tryptophan metabolism of brain in pathologic states as

these two tracers probe different enzymatic steps.

2.2 Imaging of serotonin receptors18F-Altanserin exhibits high specificity and selectivity for the 5-HT2A

receptor and is used as a radioligand in PET [73]. Previous hypothesis was

implied that post-synaptic serotonin receptors are increased in depressive

patients and anti-depressants exert their effect by down-regulation of

serotonin receptors [74]. The 5-HT2A binding potential of 18F-Altanserin in the

hippocampus was related to comorbid major depressive episode, with highest

values found in non-depressed subjects with borderline personality disorder

and lowest in healthy control subjects [75]. In obsessive-compulsive disorder,

an increase in 5-HT2A receptor binding was found in the caudate nuclei of

untreated patients [76]. However, some evidence demonstrated the paradoxical

results in patients. Mintun et al. found that hippocampal 5-HT2A receptor was

reduced in depressed patients with 18F-Altanserin/PET imaging [77].

The development of 11C-WAY-100635 [[(N-2-4-2-methoxyphenyl)-1-

piperazinyl]ethyl-N-(2-pyridinyl) cyclohexane carboxamide)], the potent and

selective 5-HT1A antagonist, as a PET imaging probe has enabled to access 5-

HT1A receptor binding in major depressive disorders and anxiety in vivo [78-

80]. Until now, the knowledge of the role of 5-HT1A and 5-HT2A receptors in

several psychiatric is still limited.

2.3 Imaging of serotonin transporter (SERT)

SERT is an essential protein for the modulation of the serotonergic

neuronal functions by controlling reuptake of serotonin in the synaptic cleft

back into the neuron terminal and is also the main target of most commonly

used antidepressants (selective serotonin reuptake inhibitors; SSRIs) and

several drugs of abuse. It is believed that depression is associated with low

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level of serotonin, thus blocking serotonin reuptake with SSRIs has been

applied in the treatment of depression. 11C-(+)McN5652 was the first promising

PET imaging agent for studying SERT in humans and considered as a marker for

integrity of the 5-HT terminals by assessing SERT density [81, 82]. Buchert et

al. found the distribution volume ratio (DVR) of 11C-(+)McN5652 in methylene-

dioxymethamphetamine (MDMA) users was significantly reduced in the

mesencephalon and the thalamus, indicating that 11C-(+)McN5652/PET may be

applied to investigate the long-term effect of the drug ecstasy on the

availability of 5-HT system [83, 84]. Nevertheless, high non-specific binding

has limited its clinical application. [18F]fluoromethyl analog of (+)McN5652

(18F-(+)-FMe-McN5652) has been synthesized recently, with the same

distribution pattern of serotonin uptake sites but a faster binding

equilibrium in piglets and a longer radioisotope half-life compared to 11C-

(+)McN5652 [85-87]. 18F-(+)-FMe-McN5652 may turn out to be the alternate for

SERT imaging of human brain although it still has limitations in full

quantification of PET data.

4-18F-ADAM is one of few 18F-labeled radioligands for studying SERT using

PET. The biodistribution, toxicity, and radiation dosimetry of 4-18F-ADAM has

been conducted in rats and primates, and the utilization of 4-18F-ADAM has

been validated in neurotoxin-, SSRIs-, and drug ecstasy-treated (ecstasy,

MDAM, 3, 4-Methylenedioxymethamphetamine) rat models, suggesting that 4-18F-

ADAM could be safe and suitable in human studies [88-93]. However, the major

drawback of 4-18F-ADAM is its relatively low radiochemical yield, and further

characterization of this new radioligand in humans is warranted.

Mapping the brain SERT with promising iodinated ADAM has been developed

recently [94]. The biodistribution of 123I-ADAM has been evaluated in both

animals and humans [95-101]. Our previous data further demonstrated the

heterogeneity of the SERT distribution in rat brains, with the highest uptake

of 123I-ADAM in the dorsal raphe nucleus, substantia nigra, lateral

hypothalamus, venral lateral geniculate nucleus, basolateral amygdala, and

ventromedial hypothalamus; the moderate uptake in the mediodorsal thalamus,

lateral dorsal thalamus, dorsal hypothalamus, dorsal lateral geniculate

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nucleus, basomedial amygdala, lateral amygdala, and hippocampus; the low

uptake in the cingulum, caudate putamen, prefrontal cortex, and cerebellum.123I-ADAM uptake was dramatically decreased in the hippocampus, thalamus,

amygdala, geniculate nuclei, hypothalamus, raphe nucleus, and substantia nigra

in p-chloroamphetamine (PCA)-treated rats [99]. 2-(2'-((dimethylamino)methyl)-

4'-iodophenylthio)benzenamine (FlipADAM) was an improved SPECT radiotracer for

selective SERT imaging. Wang et al. reported that 125I-FlipADAM exhibited

faster clearance and binding equilibrium in the brain of SD rats compared to125I-ADAM [102]. 125I-FlipADAM successfully penetrated the blood brain barrier,

as evidenced by the brain uptake at 2 min (1.75% dose/g). 125I-FlipADAM also

had a good target to non-target (hypothalamus/cerebellum) ratio of 3.35 at 60

min post-injection. The value of clinical application needs to be further

validated.

3. Molecular imaging in Neuro-oncology

Brain tumors, especially high-grade gliomas, are extremely resistant to

conventional therapies, including surgery, chemotherapy, and radiotherapy. The

5-year survival rate of patients with glioblastoma multiforme (GBM) is less

than a few percent even with aggressive combinational treatments [103, 104].

Metastatic brain tumors are also a major cause of morbidity and mortality in

human being. Therefore, there is a high medical need for new effective

therapies to treat both primary and metastatic brain tumors. There is an

increasing interest in the use of BNCT as a tumor-selective treatment for

malignant brain tumors which remain incurable despite aggressive treatment

with surgery, chemotherapy, and conventional radiotherapy. Briefly, low-energy

thermal neutrons interact with nonradioactive boron (10B) accumulated in tumor

cells, and release high-LET alpha and lithium particles (7Li) with a short

path length (10-14 m) via boron neutron capture reaction, 10B (n, α) 7Li,

thereby destroying tumor cells efficiently while sparing normal tissues [105,

106]. BNCT clinical trials have recently been initiated cancer treatment in

USA, Europoe, Japan, and Taiwan. However, the lack of selective and sufficient

accumulation of 10B carriers in tumors is still the main impediment for BNCT

10

to be successful. Small-animal models with human brain tumors have played an

essential role in the better understanding of brain tumor biology, and have

made not only a significant contribution to the improvement of 10B-carriers,

but also the treatment planning and outcome of clinical BNCT while combined

with molecular imaging.

3.1 PET/ SPECT probes for boron distribution imaging

Two boron delivery agents, boronophenylalanine (BPA) and borocaptate

sodium (BSH), have been used for clinical trials. BPA, the analogs of amino

acids phenylalanine (Phe) and tyrosine (Tyr), is incorporated into tumor cells

via active transport. To optimize the efficacy of BNCT and predict the

effectiveness of the treatment, the estimated tumor-to-normal brain ratio of10B and the time window for neutron irradiation become the hinging point

before BNCT treatment. Menichetti et al. demonstrated that the use of

[18F]FBPA and PET/CT could not only provide more effective measurement of the

tumor extraction of 10BPA compared to normal tissue in patients, but obtain a

better treatment planning of BNCT for the personalized medicine [107]. To

provide the pharmacokinetics of BPA for clinical use of BNCT in Taiwan, our

research group has synthesized and characterized 18F-FBPA-Fr using a F98

glioma-bearing rat model [108, 109]. BPA conjugated with fructose (BPA-Fr) has

been proven to increase its solubility, so that the drug uptake in tumor is

enhanced [110, 111]. In biodistribution studies, the tumor-to-normal brain

ratios of 18F-FBPA-Fr were 3.45, 3.13, 2.61, and 2.02 at 0.5, 1, 2, and 4 h

post-injection, with similar uptake characteristics to BPA-Fr (2.05, 1.86,

1.24, and 1.1, respectively) estimated by inductively coupled plasma mass

spectrometry (ICP-MP) [112, 113]. PET scanning also demonstrated that the

accumulation of radioactivity in tumor peaked at first hour and then gradually

decreased after the administration of 18F-FBPA-Fr. These results indicated

that 0.5-1 h after BPA-Fr injection would be the optimal time for tumor

irradiation, and clearly, 18F-FBPA-Fr may turn out to be a prognostic and

therapeutic indicator for patients who are poor surgical candidates and are

considered for BNCT. On the contrary, BSH does not accumulate in the normal

11

brain, but target brain tumors due to the disruption of blood-brain-barrier

(BBB). 131I has been applied to study in vivo characteristics of BSH in a

melanoma-bearing animal model, demonstrating that the pharmacokinetics and

biodistribution of 131I-BSH were consistent with the data on the dynamics of

the nonlabeled BSH distribution [114]. The knowledge concerning the

bioavailability and the metabolism of BSH is nevertheless very limited.

In the past two decades, polyhedral boron compounds, including polyhedral

boron hydrides and carboranes, have been investigated as an potential boron-

delivery agents which could achieve higher tumor-to-normal brain ratios with

low chemotoxicity in preclinical studies. Boronated amino acids, nucleic

acids, peptide, and antibodies, boronated carbohydrates, and boronated

porphyrins and phthalocyanines are of interest for the development of more

efficient BNCT [115]. Radioiodination and radiobromination of polyhedral

boranes have been proposed to study their biodistribution and pharmacokinetics

in vivo [116-119]. 67Cu and 99mTc-labelled polyhedral boranes have also been

investigated as potential imaging probes to aid BNCT treatment planning [120,

121].

3.2 Nanocarrier- and antibody-mediated delivery of boron carrier

Recently, Nanocarrier, receptor ligands, and antibodies have been

intensively studied as a very promising drug delivery system. 125I- or 76Br-

polyhedral boron coupled with anti-HER2/neu humanized antibody trastuzumab was

described for the treatment of breast cancers [116, 117]. Targeting efficiency

of radioiodinated carboranes coupled with cMAb U36 on a head and neck squamous

cell carcinoma xenograft model was evaluated [118]. However, a major

limitation of boron clusters directly linked to mAb is that the modification

of mAb can reduce its immunoreactivity. Attachment of boronated dendrimers to

mAb has been designed to deliver the requisite amount of 10B without

compromising the targeting efficiency of mAb for BNCT. Yang et al. reported

that boronated polyamidoamine dendrimer linked with anti-EGFRvIII mAb (BD-

L8A4) and cetuximab (BD-C225) retained their in vitro and in vivo

immunoreactivity, and the biodistribution of 125I-BD-mAbs was determined in F98

12

glioma-bearing rats [122]. On the other hand, the EGF-conjugated boronated

dendrimers have a much smaller MW than EGFR mAb conjugates, they should be

capable of more rapid and effective tumor targeting than has been observed

with mAbs [123, 124]. Folate receptors (FR) are up-regulated in a variety of

human cancers. Many studies have shown that radiolabeled folic acid and its

derivatives are suitable for tumor-targeting imaging of SPECT or PET in small

animal models overexpressing FR. 64Cu-porphyrin-peptide-folate (64Cu-PPF) has

been evaluated as the potential of PET probe for cancer imaging [125]. 99mTc-

labeled PEGylated dendrimer PAMAM folic acid conjugate (99mTc-G5-Ac-pegFA-DTPA)

has been synthesized to study the in vitro/in vivo stability and

biodistribution in FR+ tumor bearing mice using microSPECT [126]. As such, the

development of radiolabelled polyhedral boron moiety connected to

nanoparticles, ligand/receptor of growth factors, or tumor-targeting

monoclomoal antibodies is of great potential for the medical application of

BNCT.

Boron nitride nanotubes (BNNTs), a structural analog of a carbon nanotube

where C atoms are substituted by alternating B and N atoms, have been proposed

as delivery agents able to target high boron concentration in tumors cells for

BNCT [127]. Recently, Ciofani et al. demonstrated that BNNTs functionalized

with folic acid as a tumor targeting ligand have shown the selective

accumulation in GBM cells but not normal human fibroblasts [128]. Soares et

al. reported the biodistribution of 99mTc-functionalized BNNTs in normal Swiss

mice with SPECT imaging, revealing a potential application of 99mTc-

functionalized BNNTs as a new SPECT imaging probe applied in BNCT [129].

3.3 Clinical perspective of BNCT

Several centers in USA, Europe, Japan and Taiwan are devoted to the

development of BNCT. However, over the past few decades, BNCT has progressed

relatively slowly due to the controversial outcome from clinical trials. The

design of boron carriers and drug delivery system, the evaluation of

treatments, and the source of neutron beam will need to be optimized to

enhance the therapeutic efficacy of BNCT. The use of PET/SPECT probes to

13

select patients who are likely to respond to BNCT and the combination of

multimodality imaging strategies, such as MRI and CT for anatomical

information could accelerate the development of new boron delivery agents. We

expected that BNCT for brain tumor may protect more cognitive function than

conventional cancer therapy, and it may become the personalized therapy in the

future.

Conclusions

The knowledge and the therapeutic techniques of brain diseases and

disorders are much delayed than the other diseases. With the development of

molecular imaging, neuroimaging with PET and SPECT provides the physiologic

and metabolic changes in healthy and pathologic tissues, and therefore

facilitates the diagnosis and treatment of psychiatric disorders and the

advance of brain tumor therapy. In the future, the combination of MRI/PET or

PET/CT imaging will enable to offer both anatomical and multi-functional

information of human brain and may show added value in increasing diagnostic

accuracy and better treatment planning.

14

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