PT - JOURNAL ARTICLE AU - Jouannot, Erwan AU - d'Heilly, Sébastien AU - Carrez, Chantal TI - Preclinical investigation of anti-CEA antibody fragments as tumor imaging probes: Comparison of biodistribution and pharmacokinetics DP - 2013 May 01 TA - Journal of Nuclear Medicine PG - 1334--1334 VI - 54 IP - supplement 2 4099 - http://jnm.snmjournals.org/content/54/supplement_2/1334.short 4100 - http://jnm.snmjournals.org/content/54/supplement_2/1334.full SO - J Nucl Med2013 May 01; 54 AB - 1334 Objectives ImmunoPET using biological constructs as probes for Positron Emission Tomography (PET) represents an exciting imaging option to non-invasively demonstrate tumor targeting and quantify selective tumor uptake of biologics. In the present study a series of antibody fragments were investigated for their potential as tumor imaging probes. F(ab) and F(ab’)2 formats were derived from the anti-carcinoembryonic antigen (CEA) humanized monoclonal antibody hMN14 (labetuzumab), radiolabeled with Zirconium-89 (89Zr), and assessed in a mouse xenograft tumor model for tumor targeting, tissue biodistribution and pharmacokinetic (PK) properties in comparison with the full mAb. Methods ImmunoPET imaging was conducted on mice implanted with a patient-derived CEA-positive colorectal tumor model. The mice were imaged longitudinally at specific time points (from 1h to 7 days) following probe injection by the intravenous route. The PK profile of the radiolabeled compounds was assessed at regular time points (from 10 minutes to 7 days) post probe administration. The accumulation of the radioactive probes in tumor and normal organs was monitored by quantification of the PET signal on whole-body scans: the regions of interest were automatically extracted from the scans after registration on an anatomic atlas. Results The extent of the tumoral tissue was clearly delineated on immunoPET scans for 89Zr-F(ab’)2 and 89Zr-mAb, with a high specific tracer uptake in tumor compared to normal tissue. The tumor targeting for the F(ab’)2 was approximately one-third of the parental anti-CEA mAb (43% ID/g). The 89Zr-F(ab) tracer uptake in tumor was distinctly lower, comparable to muscle tissue with a strong and rapid uptake in the kidney (40% ID/g at 24 hours) explaining the short biological half-live No specific uptake in the tumor was visualized with 89Zr-F(ab). Conclusions 89Zr labelled anti-CEA F(ab’)2 and mAb show a potential for non-invasive monitoring of tissue/tumor biodistribution. The mAb exhibited a higher specific tumor uptake but a lower clearance than the F(ab’)2.