Radiotoxicity of systematically administered [211At]astatide in B6C3F1 and BALB/c (nu/nu) mice: a long-term survival study with histologic analysis.
OBJECTIVE
The present study undertook to establish the dose (LD) of systematically administered (via tail vein) sodium [211At]astatide that would kill 10% (LD10) of exposed animals in two mouse models and to evaluate the resulting histologic lesions.


METHODS
Three dose escalation experiments were carried out using groups of 10 3- to 4-week-old, 20 +/- 2 g B6C3F1 mice, and one dose escalation experiment was carried out with groups of 10 4- to 6-week-old, 22 +/- 2 g BALB/c (nu/nu) mice. All animals were weighed daily and checked twice daily for general health; autopsies were performed within 12 h of death.


RESULTS
The LD10 (95% confidence interval) level of free [211At]astatide at 360 days was 15.1 microCi (5.2-19.1 microCi) in B6C3F1 mice and was associated with a 37.8% weight difference from saline controls (p < 0.001). In the BALB/c (nu/nu) mice, the LD10 at 360 days was 7.7 microCi (0-14.2 microCi), while a dose of 10 microCi (0.42 microCi g(-1)) was associated with a 9.44% weight difference vs. saline controls (p < 0.05). Exclusive of the well-known effects on thyroid, [211At]astatide activity levels were associated with severe bone marrow depression, testicular atrophy, focal alopecia, and nuclear atypia of the epidermoid mucosa of the fore-stomach in the B6C3F1 mice; at activity levels approximating LD10 at 360 days, mild changes in the heart, liver, stomach, and spleen were observed. For BALB/c (nu/nu) mice, administration of 10 microCi was associated at autopsy with mild histologic lesions in the heart, stomach, liver, and spleen.


CONCLUSIONS
These studies provide a basis for the design of further investigations of [211At]-labeled compounds as therapeutic agents.
McLendon
R E
RE
Department of Pathology, Duke University Medical Center, Durham, NC, 27710, USA.
Archer
G E
GE
Garg
P K
PK
Bigner
D D
DD
Zalutsky
M R
MR
D000818:Animals; D001246:Astatine / Q000633:toxicity*; D001853:Bone Marrow / Q000528:radiation effects; D006321:Heart / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013270:Stomach / Q000473:pathology / Q000528:radiation effects; D013737:Testis / Q000473:pathology / Q000528:radiation effects; D015430:Weight Gain / Q000528:radiation effects
D001246:Astatine