Radioimmunotherapy of prostate cancer targeting human kallikrein-related peptidase 2

Summary, in English

Background: Prostate cancer ranks as the second most lethal malignancy in the Western world. Previous targeting of prostate-specific antigen and human kallikrein-related peptidase 2, two related enzymes abundantly expressed in prostatic malignancies, with radioimmunoconjugates intended for diagnostic purposes, have proven successful in rodent prostate cancer (PCa) models. In this study, we investigated the uptake and therapeutic efficacy of ¹⁷⁷Lu-m11B6, a human kallikrein-related peptidase 2 (hK2)-targeting radioimmunoconjugate in a pre-clinical setting. Methods: The murine 11B6 antibody, m11B6, with high affinity for hK2, was labeled with ¹⁷⁷Lu. Therapy planning was done from a biokinetic study in LNCaP xenografts, and therapeutic activities of ¹⁷⁷Lu-m11B6 were administered to groups of mice. Body weight and general conditions of the mice were followed over a period of 120 days. Results: The tumor uptake in LNCaP xenografts was 30 ± 8.2 % injected activity per gram 1 week post-injection. In vivo targeting was hK2-specific as verified by a 2.5-fold decrease in tumor uptake in pre-dosed xenografts or by a fourfold lower tumor accumulation in hK2-negative DU 145 xenografts. Therapy showed a dose-dependent efficacy in LNCaP xenografts treated with ¹⁷⁷Lu-m11B6. No therapeutic effect was seen in the control groups. The median survival for the lowest given activity of ¹⁷⁷Lu-m11B6 was 88 days compared to that of 38 days in mice given labeled non-specific IgG. For the higher administrated activities, total tumor regression was seen with minimal normal organ toxicity. Conclusions: We have proven the possibility of radioimmunotherapy targeting hK2 in subcutaneous prostate cancer xenografts. ¹⁷⁷Lu-m11B6 exhibited high therapeutic efficacy, with low observed toxicity. Additionally, an evaluation of the concept of pre-therapy planning using a dosimetry model was included in this radioimmunotherapy study.

• Författare: O. Vilhelmsson Timmermand; Erik Larsson; D. Ulmert; T. A. Tran; S. E. Strand
• Avdelning/ar: Tumörmikromiljö; Medicinsk strålningsfysik, Lund; Lund University Bioimaging Center; BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
• Publiceringsår: 2016-12-01
• Språk: Engelska
• Publikation/Tidskrift/Serie: EJNMMI Research
• Volym: 6
• Issue: 1
• Länkar: http://dx.doi.org/10.1186/s13550-016-0181-z
• Dokumenttyp: Artikel i tidskrift
• Förlag: BioMed Central (BMC)
• Ämne: Cancer and Oncology; Other Physics Topics
• Nyckelord: Lu; Lu-m11B6; 11B6; Dosimetry; hK2; Human kallikrein-related peptidase 2; Prostate cancer; Radioimmunotherapy
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 2191-219X