Biodistribution and scintigraphy of [111In]DTPA-adriamycin in mammary tumor-bearing rats

Abstract
The aim of this study was to develop an 111In-labeled diethylenetriamine pentaacetic acid-adrlamycin (DTPA-ADR) conjugate to image breast cancer. DTPA-ADR was synthesized by reacting adrlamycin with DTPA anhydride in the presence of carbonyldilmidazole. After dialysis (MW cut off was 500), the product was freeze-dried (yield 40–50%). An in vitro cell culture study was performed using cells from the 13762 Fischer rat mammary tumor line. Drug concentrations tested were 0.1–100μM. Blodistribution studies were conducted at 0.5, 2, 24 and 48 h in mammary tumor-bearing rats (n = 3/time Interval, 10 μCi/rat, i.v.) with 13762 cells (105 cells/ rat, s.c.). Planar imaging and autoradiograms were obtained at the same intervals. In vitro cell culture assays showed an IC50 of 0.1±0.01 μM for ADR and 7.2± 0.29 μM for DTPA-ADR, respectively. In biodistribution studies, tumor/blood uptake ratios of [111In]DTPA-ADR at 0.5, 2, 24 and 48 h were 0.55±0.17, 0.94±0.17, 3.06±0.53 and 3.66 0.35, respectively, whereas those for [111In]DTPA (control) were 1.19±0.69, 0.84±0.07, 0.56±0.10 and 0.60±0.03, respectively. The tumor uptake value (%ID/g) of [111In]DTPA-ADR at 0.5 h was 0.20±0.06. Planar Images and autoradiograms showed good visability of tumors. Biodistribution, autoradiography and radionucllde imaging of [111In]DTPA-ADR in breast tumor-bearing rats showed that tumor-to-blood ratios increased steadily between 30 min and 48 h. These results indicate that DTPA-ADR, a new cancer imaging agent, might be useful in the diagnosis of breast cancer and may predict a therapeutic effect prior to treatment.