Autoradiography and radioscintigraphy of technetium-99m-sestamibi in c-neu transgenic mice.

UNLABELLED: 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. CONCLUSION: 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.

Effects of human chorionic gonadotropin and cyclic adenosine monophosphate on progesterone secretion by the ovine placenta.

Progesterone production by the ovine placenta was investigated between d 80 and 115 of gestation. Serum progesterone concentrations in ewes ovariectomized (ovx) on d 75 of gestation were measured throughout the remainder of gestation, and after the ewes were injected with human chorionic gonadotropin (hCG) or saline on d 80 or 115. In addition, cotyledonary tissue was collected from intact ewes sacrificed on d 80 or 115 and progesterone accumulation was determined during 2 h incubation with or without pregnenolone supplementation and in the presence or absence of hCG or dibutyryl cyclic adenosine monophosphate (dbcAMP). Serum concentrations of progesterone in ovx ewes increased from 3.5 +/- .4 ng/ml on d 80 to 16.4 +/- 2.1 ng/ml on d 115 (P less than .05). That increase was coincident with a 1.5-to 4.5-fold increase in progesterone output by placental tissue in vitro. Addition of pregnenolone enhanced progesterone accumulation in all tissue incubations. Addition of dbcAMP increased progesterone accumulation in the incubation medium only when supplemented with pregnenolone. Human chorionic gonadotropin did not increase placental progesterone secretion in vivo or in vitro. The results confirm the enhanced secretion of progesterone by the ovine placenta between d 80 and 115 of gestation and indicate that the increase results primarily from increased secretory capability per unit of placenta. The tropic mechanism controlling the placental secretion of progesterone remains unclear, but the mechanism may involve elevation of intracellular cAMP.