Showing papers by "Gary J. Miller published in 1990"

Preoperative versus postoperative irradiation in the prophylaxis of heterotopic bone formation in rats.

Abstract: Irradiation treatment, commenced within 1–5 days post-surgery, reliably prophylaxes heterotopic bone formation but is painful and impairs desirable postop immobilization. To compare pre- versus post-op radiation, we bilaterally implanted bone matrix pellets into the thighs of 111 30-day-old Long Evans rats. Rats were randomized to time of radiation initiation (2 days pre-op, 1 hr pre-op, or 2 days post-op) and dose (300, 800, 1800, 2400, or 3000 cGy in 1 fraction). Pellets were removed on post-op day 16 or 48 and evaluated histologically and radiologically. Histologic analysis showed dose-related suppression in bone formation, that is, 40%, 27%, 6.8%, 2.5%, 6.4%, and 0.0% bone formed among sites receiving 0, 300, 800, 1800, 2400, and 3000 cGy, respectively. The difference in bone formation between control and irradiated implant sites was significant at every dose level in all treatment groups ( p ≤ .03). There was no statistically significant difference in overall bone formation between post-op (7.1%) and 1 hr pre-op (5.3%) groups, whereas 2 day pre-op rats formed significantly more bone (12.6%). Stratified by dose, however, there were no significant differences between treatment groups except at 800 cGy. At this dose, 2 day pre-op rats formed more bone (10.6%) than 1 hr pre-op (6.6%) or post-op (3.3%) groups. Results suggest that a) radiation given shortly prior to a stimulus inducing proliferation among multipotential cells may inhibit subsequent proliferation and/or differentiation, and b) clinical formation of heterotopic bone may be preventable via modest doses of irradiation delivered shortly prior to surgery.

Imaging of Non-Small Cell Lung Cancers with a Monoclonal Antibody, KC-4G3, Which Recognizes a Human Milk Fat Globule Antigen

Abstract: To determine the role of lung cancer tumor imaging with monoclonal antibodies directed against high molecular weight human milk fat globule antigens, we administered i.v. 111In-KC-4G3 to 24 patients with advanced non-small cell lung cancer. One mg of 111In-KC-4G3 was mixed with 0, 9, 49, 99, or 499 mg of unlabeled KC-4G3 and infused i.v. over 1 to 5 h. The mean 111In-KC-4G3 radiochemical purity was greater than 97% and the resultant immunoreactivity averaged 62%. Successful imaging of cancer sites was accomplished in 92% of 24 patients, and 57% of 91 total lesions were visualized. Successful localization of tumor sites related to size (P less than 0.001), with 81% of lesions greater than 3.0 cm in diameter, 50% of lesions 1.5 to 3 cm, and 6% of lesions less than 1.5 cm successfully imaging, and to location (P less than 0.05), with 69% of pulmonary lesions, 80% of soft tissue lesions, and only 32% of bone metastases being visualized. Nonspecific reticulo-endothelial uptake of radioactivity was a major problem. Approximately 35% of 111In was chelated to serum transferrin by 24 and 48 h after infusion. The mean t 1/2 beta for plasma radioisotope and immunoreactive KC-4G3 was 29 and 27 h,more » respectively. There was no correlation between total infused antibody dose and imaging success or between total dose and effect on 111In and KC-4G3 kinetics. Circulating free KC-4 antigen was measurable in all but one patient before study. Tumor biopsy following infusion could demonstrate antibody presence but not saturable antigen binding. We conclude that (a) 111In-KC-4G3 demonstrates successful tumor localization in non-small cell lung cancers bearing generally high expression of its antigen and (b) further investigations to diminish nonspecific radioactivity for imaging and utilization of high dose radiolabeled antibody for therapeutic intent are warranted.« less