Cellular accumulation of 18F-labelled boronophenylalanine depending on DNA synthesis and melanin incorporation: a double-tracer microautoradiographic study of B16 melanomas in vivo.
The cellular distribution of 4-borono-2-[18F]fluoro-L-phenylalanine ([18F]FBPA, an analog of p-boronophenylaline), a potential agent for boron neutron capture therapy (BNCT), and [6-3H]thymidine ([3H]Thd, a DNA precursor) in murine two B16 melanoma sublines and FM3A mammary carcinoma was studied in vivo using double-tracer microautoradiography. Tumour volume, tumour age, cell density in the tissues and the proportion of S phase cells in the cell cycle were the same in the three tumour models. Volume doubling time, which represents tumour growth rate, was fastest in B16F10, followed by B16F1 (P < 0.05), the slowest being in FM3A (P < 0.001). The rate of DNA synthesis in S phase cells corresponded to the volume doubling time. The greatest amount of [18F]FBPA was observed in S phase melanocytes and the lowest amount was found in non-S phase non-melanocytes. The [18F]FBPA accumulation was primarily related to the activity of DNA synthesis and, secondarily, to the degree of pigmentation in melanocytes. The therapeutic efficacy of BNCT with p-boronophenylalanine may be greater in melanoma that exhibits greater DNA synthesis activity and higher melanin content.
Kubota
R
R
Department of Radiology and Nuclear Medicine, Tohoku University, Sendai, Japan.
Yamada
S
S
Ishiwata
K
K
Tada
M
M
Ido
T
T
Kubota
K
K
D000818:Animals; D001345:Autoradiography; D001896:Boron Compounds / Q000493:pharmacokinetics*; D016754:Boron Neutron Capture Therapy; D002455:Cell Division / Q000502:physiology; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D004195:Disease Models, Animal; D005462:Fluorine Radioisotopes; D008297:Male; D008543:Melanins / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010858:Pigmentation / Q000502:physiology; D011877:Radionuclide Imaging
D001896:Boron Compounds; D004273:DNA, Neoplasm; D005462:Fluorine Radioisotopes; D008543:Melanins; C072915:4-borono-2-fluorophenylalanine; D010649:Phenylalanine; C033685:4-boronophenylalanine