[225Ac]Ac- and [111In]In-DOTA-trastuzumab theranostic pair: cellular dosimetry and cytotoxicity in vitro and tumour and normal tissue uptake in vivo in NRG mice with HER2-positive human breast cancer xenografts

EJNMMI Radiopharmacy and Chemistry

Table 1 Absorbed doses in HER2-positive SK-BR-3 cells exposed in vitro to [²²⁵Ac]Ac-DOTA-trastuzumab labeled at increasing specific activity (SA) in clonogenic survival assays ^a

SA (kBq/µg)	²²⁵Ac per well (Bq) ^b	Absorbed dose from 180 min treatment period (Gy)		Absorbed dose from 12 d colony-forming period (Gy)	Total absorbed dose (Gy)
SA (kBq/µg)	²²⁵Ac per well (Bq) ^b	From monolayer cells (Gy)	From medium (Gy)	Absorbed dose from 12 d colony-forming period (Gy)	Total absorbed dose (Gy)
0.15	131	0.027 ± 0.002	0.006 ± 0.000	0.47 ± 0.13	0.50 ± 0.10
0.37	328	0.069 ± 0.004	0.015 ± 0.000	1.17 ± 0.33	1.25 ± 0.30
0.74	655	0.137 ± 0.009	0.030 ± 0.000	2.35 ± 0.66	2.52 ± 0.70
1.10	982	0.206 ± 0.020	0.044 ± 0.000	3.52 ± 0.99	3.77 ± 1.00
1.66	1474	0.309 ± 0.020	0.067 ± 0.000	5.28 ± 1.49	5.66 ± 2.00

^aAbsorbed doses were estimated using the MIRD schema as described in the Methods section (Cellular Dosimetry)
^bAssumes treatment of 1 × 10⁵ cells with 300 µL of 20 nmoles/L of [²²⁵Ac]Ac-DOTA-trastuzumab labeled at the indicated SA