A Fully Automated One Pot Synthesis of 9-(4-[18F]Fluoro-3-Hydroxymethylbutyl) Guanine for Gene Therapy Studies

Peñuelas, Iván; Boan, Jose; Martí-Climent, Josep M.; Barajas, Miguel; Narvaiza, Iñigo; Satyamurthy, Nagichettiar; Barrio, Jorge R.; Richter, José A.

doi:10.1016/s1536-1632(02)00086-0

Cited by 23 publications

(8 citation statements)

References 17 publications

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“…Three-year-old captive bred female NHP weighing 2.3 kg were injected with 1.2 Â 10 12 viral particles of AdCMVHSV1-tk. 8,10 The vector was diluted in phosphate-buffered saline to a final volume of 30 ml and was then infused via a peripheral vein. We carried out the first imaging study 2 days after injection of the vector, when the expression of the transgene is believed to be maximal according to rodent studies.…”

Section: Quantitative Pet Transgene Imaging In Primatesmentioning

confidence: 99%

“…8,9 This technique is based on the injection of a PETspecific reporter probe (namely [ 18 F]9-(4-[18F]-fluoro-3-hydroxymethylbutyl)-guanine ([ 18 F]FHBG)), a fluorine-18-labelled penciclovir analogue, 10 which when phosphorylated by thymidine kinase (TK) becomes retained intracellularly. The study also concluded that the readministration of the vector to the patients failed to achieve transgene expression in the tumour, although measurable expression inside the tumour lesion could be measured following the first injection.…”

Section: Introductionmentioning

confidence: 99%

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PET imaging of thymidine kinase gene expression in the liver of non-human primates following systemic delivery of an adenoviral vector

et al. 2008

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and 4 CIBER en enfermedades hepáticas y digestivas, SpainNon-invasive in vivo imaging of transgene expression is currently providing very important means to optimize gene therapy regimes. Results in non-human primates are considered the most predictive models for the outcome in patients. In this study, we have documented that tumour and primary cell lines from human and non-human primates are comparably gene-transduced in vitro by serotype 5 adenovirus expressing HSV1-thymidine kinase. Transgene expression can be quantified in human and monkey cultured cells by positron emission tomography (PET) imaging when transduced cells are incubated with a fluoride-18 labelled penciclovir analogue. In our hands, PET images of cell cultures estimate the number of transduced cells rather than intensity of transgene expression once a threshold of TK per cell is reached. Interestingly, in vivo systemic administration of a clinical grade recombinant adenovirus expressing TK into macaques gives rise to an intense retention of the radiotracer in the liver parenchyma, providing an experimental system to visualize transgene expression that ought to be similar in human and macaques. Such imaging methodology might contribute to improve strategies based on adenoviral vectors.

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Section: Quantitative Pet Transgene Imaging In Primatesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

PET imaging of thymidine kinase gene expression in the liver of non-human primates following systemic delivery of an adenoviral vector

et al. 2008

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“…2). [13][14][16][17][18][19][20][22][23][24][25][26][27][32][33][34][35][36][37][38][39] These probes take advantage of the fact that HSV1-TK and its mutants, especially HSV1-sr39TK, have a much higher affinity for them than the cytoplasmic mammalian TKs. Amongst acycloguanosine probes, 9-(4- 18 [4][5]11,27,[34][35][36]72,[85][86][87][88][89][90][91][92][93][94][95][96][97][98][99][100][101] Regardless of sensitivity, the use of each probe has its advantages and disadvantages.…”

Section: Herpes Simplex Virus 1 Thymidine Kinase and Its Mutant Derivmentioning

confidence: 99%

PET and SPECT Reporter Gene Imaging

Yaghoubi¹

2012

Molecular Imaging Probes for Cancer Research

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“…A PET scan was obtained at day 2 using [ 18 F]FHBG (a fluorine-18 labeled penciclovir analog) as a radiotracer as described. 26 If the PET scan was positive for TK gene expression, then the study was repeated at day 9 after withdrawing valganciclovir for 24 h. Table 2 summarizes the characteristics of treated patients. Ten patients were enrolled.…”

Section: Patient Selection and Enrollmentmentioning

confidence: 99%

A phase I clinical trial of thymidine kinase-based gene therapy in advanced hepatocellular carcinoma

et al. 2010

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The aim of this phase I clinical trial was to assess the feasibility and safety of intratumoral administration of a first-generation adenoviral vector encoding herpes simplex virus thymidine kinase (HSV-TK) gene (Ad.TK) followed by systemic ganciclovir to patients with advanced hepatocellular carcinoma (HCC). Secondarily, we have analyzed its antitumor effect. Ten patients were enrolled in five dose-level cohorts that received from 10 10 to 2 Â 10 12 viral particles (vp). Ad.TK was injected intratumorally and patients received up to three doses at 30-day intervals. Positron emission tomography was used to monitor TK gene expression. Ad.TK injection was feasible in 100% of cases. Treatment was well tolerated and dose-limiting toxicity was not achieved. Cumulative toxicity was not observed. Hepatic toxicity was absent even in cirrhotic patients. Fever, flu-like syndrome, pain at the injection site and pancytopenia were the most common side effects. No partial responses were observed and 60% of patients showed tumor stabilization of the injected lesion. Importantly, two patients who received the highest dose showed signs of intratumoral necrosis by imaging procedures. One of them achieved a sustained stabilization and survived for 26 months. In conclusion, Ad.TK can be safely administered by intratumoral injection to patients with HCC up to 2 Â 10 12 vp per patient.

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A Fully Automated One Pot Synthesis of 9-(4-[18F]Fluoro-3-Hydroxymethylbutyl) Guanine for Gene Therapy Studies

Cited by 23 publications

References 17 publications

PET imaging of thymidine kinase gene expression in the liver of non-human primates following systemic delivery of an adenoviral vector

PET imaging of thymidine kinase gene expression in the liver of non-human primates following systemic delivery of an adenoviral vector

PET and SPECT Reporter Gene Imaging

A phase I clinical trial of thymidine kinase-based gene therapy in advanced hepatocellular carcinoma

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