title: Intratherapeutic biokinetic measurements, dosimetry parameter estimates, and monitoring of treatment efficacy using cerenkov luminescence imaging in preclinical radionuclide therapy.
abstract: In recent years, there has been increasing interest in noninvasive Cerenkov luminescence imaging (CLI) of in vivo radionuclide distribution in small animals, a method proven to be a high-throughput modality for confirmation of tracer uptake. 11B6 is an IgG1 monoclonal antibody that is specific to free human kallikrein-related peptidase 2, an antigen abundant in malignant prostatic tissue. Free human kallikrein-related peptidase 2 was targeted in prostate cancer xenografts using (177)Lu-labeled 11B6 in either murine or humanized forms for radionuclide therapy. In this setting, CLI was investigated as a tool for providing parameters of dosimetric importance during radionuclide therapy. First, longitudinal imaging of biokinetics using CLI and SPECT was compared. Second, the CLI signal was correlated to quantitative ex vivo tumor activity measurements. Finally, CLI was used to monitor the radionuclide treatment, and the integrated CLI radiance was found to correlate well with subject-specific tumor volume reduction.
  
  
  METHODS
  11B6 was radiolabeled with (177)Lu through the CHX-A″-DTPA chelator. In vivo CLI and SPECT imaging of (177)Lu-DTPA-11B6 uptake was performed on NMRI and BALB/c nude mice with subcutaneous LNCaP xenografts up to 14 d after injection. Tumor size was measured to assess response to radionuclide therapy.
  
  
  RESULTS
  CLI correlated well with SPECT imaging and could be applied up to 14 d after injection of 20 MBq with the specific tracer used. Through integration of the CLI radiance as a function of time, a dose metric for the tumors could be formed that correlated exponentially with tumor volume reduction.
  
  
  CONCLUSIONS
  CLI provided valuable intratherapeutic biokinetic measurements for treatment monitoring and could be used as a tool for subject-specific absorbed dose estimation.
authors: Department of Medical Radiation Physics, Lund University, Lund, Sweden.
authors: Oskar Vilhelmsson
authors: OV
authors: Timmermand
authors: Lund University Bioimaging Center, Lund University, Lund, Sweden; and.
authors: Thuy A
authors: TA
authors: Tran
authors: Department of Medical Radiation Physics, Lund University, Lund, Sweden Lund University Bioimaging Center, Lund University, Lund, Sweden; and.
authors: Sven-Erik
authors: SE
authors: Strand
authors: Division of Atomic Physics, Department of Physics, Lund University, Lund, Sweden Johan.Axelsson@fysik.lth.se.
authors: Johan
authors: J
authors: Axelsson
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D019540:Area Under Curve; D045744:Cell Line, Tumor; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D007610:Kallikreins / Q000737:chemistry; D007700:Kinetics; D049449:Luminescence; D008163:Luminescent Measurements / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015233:Models, Statistical; D057054:Molecular Imaging; D009368:Neoplasm Transplantation; D055095:Optics and Photonics; D019047:Phantoms, Imaging; D011471:Prostatic Neoplasms / Q000473:pathology; D011868:Radioisotopes / Q000627:therapeutic use*; D011874:Radiometry / Q000379:methods*; D019275:Radiopharmaceuticals; D011878:Radiotherapy / Q000379:methods*; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D007610:Kallikreins
keywords: 177Lu-DTPA-11B6; Cerenkov luminescence imaging; dosimetry; human kallikrein gene family; human kallikrein related peptidase 2; molecular imaging; optical imaging; prostate cancer; radionuclide therapy