Preclinical comparison of [¹¹¹In]In-BPAMD and [^99mTc]Tc-DPD for SPECT/CT-based bone imaging

Our goal was to establish a preclinical model that simulates prostate cancer (PCa)-derived, but PSMA-negative (PSMA^-) bone metastasis, which can be visualized via single-photon emission computed tomography (SPECT) and to compare ¹¹¹In- and ^99mTc-labeled bone-seeking agents, ideally by using this animal model.

Intraosseous (i.o.) inoculations of PC-3 cells (5 × 10⁵) were conducted in 10-to-11-week-old male CB-17 SCID mice (n = 6). Over a period of three weeks, 19.6-81.1 MBq (0.03-0.12 mg, n = 18) [^99mTc]Tc-DPD was injected once per week into treated mice and bone lesion formation was investigated by μSPECT/CT (2 h/4 h and 22-23 h post injectionem (p.i.)). 48.9-78.7 MBq (0.03-0.04 mg or 44.8-72.7 nmol, n = 6) [¹¹¹In]In-BPAMD was injected in healthy, non-treated 10-to-14-week-old male CB-17 SCID mice (n = 4) and skeletal uptake investigated by μSPECT/CT (2 h and 22-24 h p.i.).

In comparison to the untreated tibia or femur, no increased uptake of [^99mTc]Tc-DPD could be visualized by μSPECT/CT in the i.o. inoculated tibia or femur. [^99mTc]Tc-DPD showed considerable uptake throughout the entire skeleton of the mice (9.02% ID/mL in the spine) and surpassed bone uptake of [¹¹¹In]In-BPAMD (0.28% ID/mL) by a factor of 32 at 2 h p.i. Biodistribution studies at 23-24 h p.i. confirmed these results.

[¹¹¹In]In-BPAMD could not compete with [^99mTc]Tc-DPD in μSPECT/CT imaging of bone structures in CB-17 SCID mice. In this proof-of-concept study, a preclinical model for PCa-derived bone metastasis, which exhibits enhanced uptake of [^99mTc]Tc-DPD could not be established by intraosseous inoculation of PC-3 cells in CB-17 SCID mice.