Selective uptake of p-boronophenylalanine by osteosarcoma cells for boron neutron capture therapy.
Osteosarcoma is the most common non-hematologic primary cancer type that develops in bone. Current osteosarcoma treatments combine multiagent chemotherapy with extensive surgical resection, which in some cases makes necessary the amputation of the entire limb. Nevertheless its infiltrative growth leads to a high incidence of local and distant recurrences that reduce the percentage of cured patients to less than 60%. These poor data required to set up a new therapeutic approach aimed to restrict the surgical removal meanwhile performing a radical treatment. Boron neutron capture therapy (BNCT), a particular radiotherapy based on the nuclear capture and fission reactions by atoms of (10)B, when irradiated with thermal neutrons, could be a valid alternative or integrative option in case of osteosarcoma management, thanks to its peculiarity in selectively destroying neoplastic cells without damaging normal tissues. Aim of the present work is to investigate the feasibility of employing BNCT to treat the limb osteosarcoma. Boronophenylalanine (BPA) is used to carry (10)B inside the neoplastic cells. As a first step the endocellular BPA uptake is tested in vitro on the UMR-106 osteosarcoma cell line. The results show an adequate accumulation capability. For the in vivo experiments, an animal tumor model is developed in Sprague-Dawley rats by means of an intrafemoral injection of UMR-106 cells at the condyle site. The absolute amounts of boron loading and the tumor to normal tissue (10)B ratio are evaluated 2 h after the i.v. administration of BPA. The boron uptake by the neoplastic tissue is almost twice the normal one. However, higher values of boron concentration in tumor are requested before upholding BNCT as a valid therapeutic option in the treatment of osteosarcoma.
Ferrari
C
C
Department of Surgery, Experimental Surgery Laboratory, University of Pavia, Piazza Botta, Pavia, Italy. ferraric@unipv.it
Zonta
C
C
Cansolino
L
L
Clerici
A M
AM
Gaspari
A
A
Altieri
S
S
Bortolussi
S
S
Stella
S
S
Bruschi
P
P
Dionigi
P
P
Zonta
A
A
D000818:Animals; D001693:Biological Transport, Active; D001859:Bone Neoplasms / Q000378:metabolism / Q000532:radiotherapy; D001896:Boron Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D066298:In Vitro Techniques; D007554:Isotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D012516:Osteosarcoma / Q000378:metabolism* / Q000532:radiotherapy*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D001896:Boron Compounds; D007554:Isotopes; D011838:Radiation-Sensitizing Agents; D010649:Phenylalanine; C033685:4-boronophenylalanine