Na2B12H11SH (BSH) in combination with systemic hyaluronidase: a promising concept for boron neutron capture therapy for glioblastoma.
OBJECTIVE
In an attempt to optimize the therapeutic potential of Na2B12H11SH (BSH) for boron neutron capture therapy for glioblastoma, the present study investigates the influence of systemically applied hyaluronidase (a glycolytic enzyme that enhances the activity of chemotherapeutic agents in different types of cancer) on the biodistribution of BSH in patients with glioblastoma.


METHODS
Patients in two uniform groups (Groups A and B, each of which had 10 patients with histologically confirmed glioblastomas) received BSH at a dose used in earlier therapeutic trials (75 mg/kg of body weight, administered intravenously) 24 hours before surgical debulkment. Patients from Group B received additional hyaluronidase (200,000 IU, administered intravenously) immediately before BSH infusion. Boron concentrations were analyzed by inductively coupled plasma-atomic emission spectroscopy.


RESULTS
The application of hyaluronidase was associated with a statistically significant improvement in the tumor (maximum)-to-blood concentration ratio of 1.83 (range, 0.68-3.67) compared with 1.31 (range, 0.8-1.78) with BSH alone. Moreover, with the use of hyaluronidase, there was a tendency for a higher maximal concentration in tumor (not statistically significant). Boron accumulation in glioblastoma tissue was highly selective in both groups, with tumor-to-healthy brain concentration ratios ranging from 6:1 to 20:1.


CONCLUSIONS
These preliminary data suggest that hyaluronidase improves BSH biodistribution and, consequently, the therapeutic potential of this boron carrier. This finding might be of clinical value in the future.
Haselsberger
K
K
Department of Neurosurgery, Karl Franzens University, Graz, Austria.
Radner
H
H
Pendl
G
G
D000328:Adult; D000368:Aged; D001682:Biological Availability; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D001894:Borohydrides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D001932:Brain Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy; D003399:Craniotomy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005909:Glioblastoma / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018714:Radiotherapy, Adjuvant; D013438:Sulfhydryl Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics
D001894:Borohydrides; D011838:Radiation-Sensitizing Agents; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate; D006821:Hyaluronoglucosaminidase