Positron emission tomography reporter gene strategy for use in the central nervous system

There is a growing need for monitoring or imaging gene therapy in the central nervous system (CNS). This can be achieved with a positron emission tomography (PET) reporter gene strategy. Here we report the development of a PET reporter gene system using the PKM2 gene with its associated radiotracer [18F]DASA-23. The PKM2 reporter gene was delivered to the brains of mice by adeno-associated virus (AAV9) via stereotactic injection. Serial PET imaging was carried out over 8 wk to assess PKM2 expression. After 8 wk, the brains were excised for further mRNA and protein analysis. PET imaging at 8 wk post-AAV delivery showed an increase in [18F]DASA-23 brain uptake in the transduced site of mice injected with the AAV mice over all controls. We believe PKM2 shows great promise as a PET reporter gene and to date is the only example that can be used in all areas of the CNS without breaking the blood–brain barrier, to monitor gene and cell therapy.

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Role of Positron Emission Tomography for Central Nervous System Involvement in Systemic Autoimmune Diseases: Status and Perspectives

Current Medicinal Chemistry ◽

10.2174/0929867324666170523144402 ◽

2018 ◽

Vol 25 (26) ◽

pp. 3096-3104 ◽

Cited By ~ 3

Author(s):

Daniele Mauro ◽

Gaetano Barbagallo ◽

Salvatore D`Angelo ◽

Pasqualina Sannino ◽

Saverio Naty ◽

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Keyword(s):

Positron Emission Tomography ◽

Central Nervous System ◽

Nervous System ◽

Autoimmune Diseases ◽

Pet Imaging ◽

Emission Tomography ◽

Cns Involvement ◽

Systemic Autoimmune Diseases ◽

Positron Emission

In the last years, an increasing interest in molecular imaging has been raised by the extending potential of positron emission tomography [PET]. The role of PET imaging, originally confined to the oncology setting, is continuously extending thanks to the development of novel radiopharmaceutical and to the implementation of hybrid imaging techniques, where PET scans are combined with computed tomography [CT] or magnetic resonance imaging[MRI] in order to improve spatial resolution. Early preclinical studies suggested that 18F–FDG PET can detect neuroinflammation; new developing radiopharmaceuticals targeting more specifically inflammation-related molecules are moving in this direction. Neurological involvement is a distinct feature of various systemic autoimmune diseases, i.e. Systemic Lupus Erythematosus [SLE] or Behcet’s disease [BD]. Although MRI is largely considered the gold-standard imaging technique for the detection of Central Nervous System [CNS] involvement in these disorders. Several patients complain of neuropsychiatric symptoms [headache, epilepsy, anxiety or depression] in the absence of any significant MRI finding; in such patients the diagnosis relies mainly on clinical examination and often the role of the disease process versus iatrogenic or reactive forms is doubtful. The aim of this review is to explore the state-of-the-art for the role of PET imaging in CNS involvement in systemic rheumatic diseases. In addition, we explore the potential role of emerging radiopharmaceutical and their possible application in aiding the diagnosis of CNS involvement in systemic autoimmune diseases.

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