Autoradiography and radioscintigraphy of technetium-99m-sestamibi in c-neu transgenic mice.
Intratumor distribution patterns of 99mTc-sestamibi and 14C-2-deoxy-D-glucose were compared in the c-neu OncoMouse, a transgenic mouse that spontaneously develops breast tumors.


METHODS
Thirty or 60 min after intravenous injection of 5 muCi 14C-2-deoxy-D-glucose and 3 mCi 99mTc-sestamibi into mice (n = 3 per time point) bearing mammary tumors (0.3-1.5 cm), the animals were analyzed for organ and tumor distribution using dual-label, whole-body autoradiography. The retention patterns of the two compounds were related to tumor morphology and viability, based on H&E-stained adjacent sections. For imaging studies, the transgenic mice (n = 9) were anesthetized with pentobarbital, injected intravenously with 5-20 mCi 99mTc-sestamibi and imaged for 60 min using a gamma camera equipped with a 1-mm pinhole collimator.


RESULTS
All positively stained tumors retained both agents, with a mean 99mTc-sestamibi tumor retention of 0.38% +/- 0.2% ID/g at 30 min compared to 4.18% +/- 0.62% ID/g for 14C-2-deoxy-D-glucose. Tumor retention of the agents remained the same at 60 min, and neither compound localized within necrotic or cystic regions of the neoplasms. Repeat imaging at 2-8-day intervals indicated a predicted sensitivity to detect a 30% difference in tumor retention of a test versus reference compound in preclinical screening.


CONCLUSIONS
The c-neu OncoMouse is a useful model for in vivo imaging and provides a spontaneous tumor model for preclinical screening of breast tumor imaging agents.
Crane
P D
PD
Radiopharmaceutical Division, DuPont Merck Pharmaceutical Co., North Billerica, Massachusetts 01862, USA.
Onthank
D C
DC
Bourque
C R
CR
Heminway
S J
SJ
Mazaika
T J
TJ
Leav
I
I
Zambuto
G F
GF
Lazewatsky
J L
JL
Villamil-Perez
L
L
Carroll
T R
TR
D000818:Animals; D001345:Autoradiography; D002250:Carbon Radioisotopes; D003847:Deoxyglucose; D005260:Female; D018734:Genes, erbB-2; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging*; D051379:Mice; D008822:Mice, Transgenic; D011877:Radionuclide Imaging; D017256:Technetium Tc 99m Sestamibi; D013794:Thallium Radioisotopes; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D013794:Thallium Radioisotopes; D017256:Technetium Tc 99m Sestamibi; D003847:Deoxyglucose