TY - JOUR T1 - Radioimmunoimaging and Radioimmunotherapy of Prostate Cancer. Preclinical evaluation of kallikrein related peptidase 2 targeting JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1236 LP - 1236 VL - 56 IS - supplement 3 AU - Oskar Vilhelmsson Timmermand AU - Thuy Tran AU - Johan Axelsson AU - Jörgen Elgqvist AU - David Ulmert AU - Sven-Erik Strand Y1 - 2015/05/01 UR - http://jnm.snmjournals.org/content/56/supplement_3/1236.abstract N2 - 1236 Objectives Radioimmunoimaging and -therapy of prostate cancer was investigated pre-clinically by targeting the human kallikrein-related peptidase 2 (hK2). hK2 is an antigen that is over-expressed in prostatic neoplasms and is closely related to prostate-specific antigen. The anti-hK2 monoclonal antibody 11B6 was radiolabelled with 111In or 177Lu for targeting of hK2-expressing LNCaP xenografts in nude or SCID mice.Methods Biodistribution, pre-clinical SPECT/CT imaging, Cerenkov Luminescence Imaging, dosimetry calculations and therapy studies were performed to evaluate the targeting properties and therapeutic efficacy of 111In-m11B6, 177Lu-m11B6 and 177Lu-h11B6.Results SPECT/CT imaging showed that 111In-m11B6 targeted specifically hK2 and could clearly visualize the subcutaneous and intra-tibial LNCaP xenografts. Therapy studies of LNCaP xenograft models showed distinctive effects on the tumor volume and survival compared to the control groups. 177Lu-m11B6 gave a median survival close to 100% at 120 days when 36 MBq of activity was administrated. The humanized 177Lu-h11B6 showed a median survival of 77 days when 16 MBq was administrated compared to that of 37 days for the control groups and a reversible myeloid toxicity could be seen. The correlation between CLI and SPECT was good as well as the correlation between CLI and ex vivo specific uptake measurements. The presented normalization schemes can serve as a first approach to relating the CLI radiance to the specific uptake (%IA/g) in subcutaneous xenografts.Conclusions Human kallikrein-related peptidase 2 targeting was thus shown to be feasible in both radioimmunoimaging and -therapy. CLI was successfully explored as a rapid and inexpensive tool to evaluate uptake in subcutaneous xenografts and showed high potential for use for absorbed dose estimates.Research Support Swedish Cancer Foundation, The Swedish Science Council, Mrs Berta Kamprad's Foundation and Gunnar Nilsson's Foundation. ER -