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

The aim of this study was to develop an In-111-labeled diethylenetriamine p entaacetic acid-adriamycin (DTPA-ADR) conjugate to image breast cancer. DTP A-ADR was synthesized by reacting adriamycin with DTPA anhydride in the pre sence of carbonyldiimidazole. After dialysis (MW cut off was 500), the prod uct was freeze-dried (yield 40-50%), An in vitro cell culture study was per formed using cells from the 13762 Fischer rat mammary tumor line. Drug conc entrations tested were 0.1-100 mu M. Biodistribution studies were conducted at 0.5, 2, 24 and 48 h in mammary tumor-bearing rats (n = 3/time interval, 10 mu Ci/ rat, i.v.) with 13762 cells (10(6) cells/rat, s.c.). Planar imag ing and autoradiograms were obtained at the same intervals. In vitro cell c ulture assays showed an ICS, of 0.1 +/- 0.01 mu M for ADR and 7.2 +/- 0.29 mu M for DTPA-ADR, respectively. In biodistribution studies, tumor/blood up take ratios of [In-111]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 [In-111]DTPA (control) were 1.19 +/- 0.69, 0.84 +/- 0.07, 0.56 +/- 0.1 0 and 0.60 +/- 0.03, respectively, The tumor uptake value (%ID/g) of [In-11 1]DTPA-ADR at 0.5 h was 0.20 +/- 0.06. Planar images and autoradiograms sho wed good visability of tumors, Biodistribution, autoradiography and radionu clide imaging of [In-111]DTPA-ADR in breast tumor-bearing rats showed that tumor-to-blood ratios increased steadily between 30 min and 48 h, These res ults 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. [(C) 1999 Lippincott Williams & Wilkins,]