Differential Effects of Predosing on Tumor and Tissue Uptake of an111In-Labeled Anti-TENB2 Antibody–Drug Conjugate

• DOI: 10.2967/jnumed.112.103168
• Publication Date: 2012-08-08T04:49:46Z
• Authors: C. Andrew Boswell; Eduardo E. Mundo; Crystal Zhang; Shannon L. Stainton; Shang-Fan Yu; Jennifer A. Lacap; Weiguang Mao; Katherine R. Kozak; Aimee Fourie; Paul Polakis; Leslie A. Khawli; Kedan Lin
• Keywords: Biodistribution; Antibody-drug conjugate; Conjugate

TENB2, also known as tomoregulin or transmembrane protein with epidermal growth factor–like and 2 follistatin-like domains, is a proteoglycan overexpressed in human prostate tumors. This promising target for antimitotic monomethyl auristatin E (MMAE)–based antibody–drug conjugate (ADC) therapy. Nonlinear pharmacokinetics normal mice suggested that antigen expression tissues may contribute to targeted mediated disposition. We evaluated predosing strategy unconjugated antibody block ADC uptake target-expressing mouse model while striving preserve tumor efficacy. <b>Methods:</b> Unconjugated, unlabeled was preadministered bearing the TENB2-expressing explant model, LuCaP 77, followed by single administration of ¹¹¹In-labeled anti-TENB2-MMAE biodistribution SPECT/CT studies. A tumor-growth-inhibition study conducted determine pharmacodynamic consequences predosing. <b>Results:</b> Preadministration anti-TENB2 at 1 mg/kg significantly increased blood exposure radiolabeled reduced intestinal, hepatic, splenic not affecting accretion. Similar tumor-to-heart ratios were measured 24 h without predose. Consistent this, preadministration 0.75 did interfere efficacy tumor-growth dosed mg 2.5 per kilogram. <b>Conclusion:</b> Overall, potential mask peripheral, nontumor preserving could ameliorate toxicity affect future dosing strategies ADCs.