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Assessment of Treatment Response by Autoradiography with 14C-Aminocyclopentane Carboxylic Acid, 67Ga-DTPA, and 18F-FDG in a Herpes Simplex Virus Thymidine Kinase/Ganciclovir Brain Tumor Model

Tadashi Miyagawa, MD1,2, Takamitsu Oku, MD1,3, Toshio Sasajima, MD1,4, Rovathi Dasai, MS1, Bradley Beattie, BS1, Ronald Finn, PhD5, Juri Gelovani Tjuvajev, MD, PhD1 and Ronald Blasberg, MD1

1 Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York
2 Department of Neurosurgery, Chiba University Graduate School of Medicine, Chiba, Japan
3 Department of Neurosurgery, Miyazaki Medical College, Miyazaki, Japan
4 Neurosurgical Service, Akita University Hospital, Akita, Japan
5 Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York



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FIGURE 1. Corresponding images from 2 intracerebral RG2TK+ xenografts: one treated with gancyclovir (A–D) and the other treated with normal saline (control; E–H). From left to right are toluidine blue-stained histology (A and E) and parametric images of R measured with 18F-FDG (B and F), K1 of 14C-ACPC (C and G), and K1 of 67Ga-DTPA (D and H). Histology and parametric images for each animal were obtained from same tissue section. Parametric images are color coded to a range of values. Tumor outline (in red) was drawn on histologic image and electronically transferred to previously registered autoradiographic images.

 


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FIGURE 2. (A and B) Photomicrographs of RG2TK+ xenografts after 3 d of GCV treatment (A) and normal saline treatment (B). (toluidine blue, x200) (C–F) TdT-mediated dUTP-X nick-end labeling (TUNEL) staining of RG2TK+ tumor treated with GCV (C) and normal saline (D) and normal brain in treated animal (E) and nontreated animal (F). (x200)

 


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FIGURE 3. Microphotographs of immunostaining for CD34, LAT1, and 4F2hc. CD34-positive endothelial cells also express LAT1 and 4F2hc in normal brain (A) and some intratumoral vessels in CGV-treated tumor (B) and in nontreated tumor (C). However, some microvessels in GCV-treated tumor expressing CD34 were stained weakly or marginally by LAT1, whereas CD98 staining intensity was relatively retained (arrows) despite microvessel in normal brain around tumor that remained LAT1 positive (asterisks).

 


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FIGURE 4. Microphotographs of immunostaining for LAT1 and 4F2hc in nontreated tumor and in GCV-treated tumor. (Top, x100; bottom, x200)

 


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FIGURE 5. Survival of animals bearing intracerebral RG2TK+ xenografts after 3 d of treatment with GCV ({circ}) or normal saline ({square}). Three GCV-treated long-term survivors are not included in plot.

 





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