Pretreatment with Haloperidol Reduces<sup>123</sup>I-FP-CIT Binding to the Dopamine Transporter in the Rat Striatum: An In Vivo Imaging Study with a Dedicated Small-Animal SPECT Camera

Nikolaus, Susanne; Antke, Christina; Kley, Konstantin; Beu, Markus; Wirrwar, A.; Müller, Hans‐Wilhelm

doi:10.2967/jnumed.109.061952

Cited by 24 publications

(22 citation statements)

References 37 publications

(58 reference statements)

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“…Indeed, high doses of the neuropsychotic haloperidol resulted in a reduction in striatal ( 123 I)FP-CIT binding by 25% in rats 35. However, in another rat study, this could not be replicated 36.…”

Section: Discussionmentioning

confidence: 92%

(¹²³I)FP-CIT SPECT in suspected dementia with Lewy bodies: a longitudinal case study

et al. 2013

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ObjectivesLittle is known regarding the ‘false-negative’ or ‘false-positive’ striatal dopamine transporter binding on SPECT for the diagnosis of dementia with Lewy bodies (DLB). We explored the clinical course in patients fulfilling the criteria for clinical DLB with a normal (123I)FP-CIT SPECT (ie, SPECT scan negative, clinical features positive (S−CF+)) and patients not fulfilling DLB criteria with an abnormal scan (S+CF−).DesignLongitudinal case study over 2–5 years.SettingConsecutive referrals of patients with mild dementia to dementia clinics in western Norway.Participants50 patients (27 men and 23 women; mean age at baseline of 74 (range 52–88)) with (123I)FP-CIT SPECT images underwent cluster analysis: 20/50 patients allocated to a ‘DLB’ and 8 to a ‘non-DLB’ cluster were included.Outcome measuresScores on standardised clinical rating scales for hallucinations, parkinsonism, fluctuations, rapid eye movement (REM) sleep behaviour disorder and visually rated (123I)FP-CIT SPECT.ResultsDuring the follow-up period, in the S+CF− group (n=7), frequency and severity of DLB symptoms tended to increase, particularly parkinsonism (7/7) and cognitive fluctuations (7/7), while severity of visual hallucinations and REM sleep behaviour disorder remained stable. The S−CF+ (n=3) fulfilled the operationalised criteria for probable DLB both at baseline and at the end of the follow-up.ConclusionsThe findings suggest that systematic visual analyses of (123I)FP-CIT SPECT can detect people with DLB prior to the development of the full clinical syndrome. In addition, the study indicates that some patients fulfilling clinical criteria for probable DLB have a normal scan, and further studies are required to characterise these patients better.

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Section: Discussionmentioning

confidence: 92%

(¹²³I)FP-CIT SPECT in suspected dementia with Lewy bodies: a longitudinal case study

et al. 2013

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“…First, DRBAs may have neurotoxic effects on dopamine neurons; therefore, longer exposure of dopamine receptors to DRBAs may increase the toxic effects of DRBAs on presynaptic dopaminergic neurons. Although, theoretically, DRBAs should have almost no effect on DAT imaging in the striatum [24], a previous in vivo study showed that acute administration of haloperidol reduced DAT uptake in the rat striatum, suggesting that DRBAs induce a change in dopamine release to the synaptic cleft and a decrease in dopamine reuptake via DAT-binding sites [25]. In addition, a decrease in striatal DAT binding was recently reported in schizophrenic patients taking short-term antipsychotic drugs [26], suggesting that DRBAs have neurotoxic properties for dopamine neurons.…”

Section: Discussionmentioning

confidence: 98%

Clinical features of drug-induced parkinsonism based on [18F] FP-CIT positron emission tomography

Shin

Kim

et al. 2014

Neurol Sci

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Drug-induced parkinsonism (DIP) is the common cause of parkinsonism. It is difficult to make a differentiation between DIP and Parkinson's disease (PD) because there are no notable differences in the clinical characteristics between the two entities. In this study, we examined the relationship between the characteristics of [(18)F] fluorinated-N-3-fluoropropyl-2-β-carboxymethoxy-3-β-(4-iodophenyl)nortropane (FP-CIT) positron emission tomography (PET) images and clinical features in DIP patients. We retrospectively studied 76 patients with DIP who underwent [(18)F] FP-CIT PET. We also enrolled 16 healthy controls who underwent it. We compared the clinical characteristics between the DIP patients with normal [(18)F] FP-CIT PET scans and those with abnormal ones. Symmetric parkinsonism was more frequent in the patients with normal [(18)F] FP-CIT PET scans as compared with those with abnormal ones. Interval from drug intake to onset of parkinsonism was longer in the patients with abnormal [(18)F] FP-CIT PET scans as compared with those with normal ones. A semi-quantitative analysis showed that specific to non-specific binding ratios in the putamen was lower in the patients with abnormal [(18)F] FP-CIT PET scans as compared with those with normal ones and the age-matched control group. Our results suggest that symmetric parkinsonism was more prevalent, and the duration of drug exposure before the onset of parkinsonism was shorter in the patients with normal [(18)F] FP-CIT PET scans as compared with those with abnormal ones.

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“…Nikolaus et al argued that the haloperidol-induced dopamine release may compete with 123 I-FP-CIT binding (7). After dopamine is released, it is rapidly taken up as a substrate via DAT (17).…”

Section: Discussionmentioning

confidence: 99%

Acute Administration of Haloperidol Does Not Influence ¹²³I-FP-CIT Binding to the Dopamine Transporter

et al. 2014

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A recent 123 I-FP-CIT ( 123 -I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane) SPECT study on rats suggested that a single 1 mg/kg dose of the antipsychotic haloperidol induces enough dopamine release to compete with 123 I-FP-CIT for binding to the dopamine transporter. Taking into account the far-reaching consequences of this proposition, we were interested in testing whether we could reproduce this finding using storage phosphor imaging. Methods: Twenty rats were pretreated with saline or haloperidol (1 mg/kg of body weight) and then injected with 123 I-FP-CIT. Two hours after 123 I-FP-CIT injection, the rats were sacrificed and binding in the striatum, nucleus accumbens, and cerebellum (nonspecific binding) was measured. Results: In contrast to the earlier SPECT finding, acute administration of haloperidol did not induce a significant change in 123 I-FP-CIT binding ratios in the striatum and nucleus accumbens. Conclusion: Changes in synaptic dopamine due to acute haloperidol administration were not detectable with 123 I-FP-CIT.

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Pretreatment with Haloperidol Reduces¹²³I-FP-CIT Binding to the Dopamine Transporter in the Rat Striatum: An In Vivo Imaging Study with a Dedicated Small-Animal SPECT Camera

Cited by 24 publications

References 37 publications

(¹²³I)FP-CIT SPECT in suspected dementia with Lewy bodies: a longitudinal case study

(¹²³I)FP-CIT SPECT in suspected dementia with Lewy bodies: a longitudinal case study

Clinical features of drug-induced parkinsonism based on [18F] FP-CIT positron emission tomography

Acute Administration of Haloperidol Does Not Influence ¹²³I-FP-CIT Binding to the Dopamine Transporter

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Pretreatment with Haloperidol Reduces123I-FP-CIT Binding to the Dopamine Transporter in the Rat Striatum: An In Vivo Imaging Study with a Dedicated Small-Animal SPECT Camera

Cited by 24 publications

References 37 publications

(123I)FP-CIT SPECT in suspected dementia with Lewy bodies: a longitudinal case study

(123I)FP-CIT SPECT in suspected dementia with Lewy bodies: a longitudinal case study

Clinical features of drug-induced parkinsonism based on [18F] FP-CIT positron emission tomography

Acute Administration of Haloperidol Does Not Influence 123I-FP-CIT Binding to the Dopamine Transporter

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Pretreatment with Haloperidol Reduces¹²³I-FP-CIT Binding to the Dopamine Transporter in the Rat Striatum: An In Vivo Imaging Study with a Dedicated Small-Animal SPECT Camera

(¹²³I)FP-CIT SPECT in suspected dementia with Lewy bodies: a longitudinal case study

(¹²³I)FP-CIT SPECT in suspected dementia with Lewy bodies: a longitudinal case study

Acute Administration of Haloperidol Does Not Influence ¹²³I-FP-CIT Binding to the Dopamine Transporter