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

The aim of this study was to develop an ¹¹¹In-labeled diethylenetriamine pentaacetic acid-adriamycin (DTPA-ADR) conjugate to image breast cancer. DTPA-ADR was synthesized by reacting adriamycin with DTPA anhydride in the presence of carbonyldiimidazole. 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 0.1-100 μM. Biodistribution 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 (10⁶ 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 radionuclide 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.