title: Quantitative immunoPET of prostate cancer xenografts with 89Zr- and 124I-labeled anti-PSCA A11 minibody.
abstract: Prostate stem cell antigen (PSCA) is expressed on the cell surface in 83%-100% of local prostate cancers and 87%-100% of prostate cancer bone metastases. In this study, we sought to develop immunoPET agents using (124)I- and (89)Zr-labeled anti-PSCA A11 minibodies (scFv-CH3 dimer, 80 kDa) and evaluate their use for quantitative immunoPET imaging of prostate cancer.
  
  
  METHODS
  A11 anti-PSCA minibody was alternatively labeled with (124)I- or (89)Zr-desferrioxamine and injected into mice bearing either matched 22Rv1 and 22Rv1×PSCA or LAPC-9 xenografts. Small-animal PET data were obtained and quantitated with and without recovery coefficient-based partial-volume correction, and the results were compared with ex vivo biodistribution.
  
  
  RESULTS
  Rapid and specific localization to PSCA-positive tumors and high-contrast imaging were observed with both (124)I- and (89)Zr-labeled A11 anti-PSCA minibody. However, the differences in tumor uptake and background uptake of the radiotracers resulted in different levels of imaging contrast. The nonresidualizing (124)I-labeled minibody had lower tumor uptake (3.62 ± 1.18 percentage injected dose per gram [%ID/g] 22Rv1×PSCA, 3.63 ± 0.59 %ID/g LAPC-9) than the residualizing (89)Zr-labeled minibody (7.87 ± 0.52 %ID/g 22Rv1×PSCA, 9.33 ± 0.87 %ID/g LAPC-9, P < 0.0001 for each), but the (124)I-labeled minibody achieved higher imaging contrast because of lower nonspecific uptake and better tumor-to-soft-tissue ratios (22Rv1×PSCA:22Rv1 positive-to-negative tumor, 13.31 ± 5.59 (124)I-A11 and 4.87 ± 0.52 (89)Zr-A11, P = 0.02). Partial-volume correction was found to greatly improve the correspondence between small-animal PET and ex vivo quantification of tumor uptake for immunoPET imaging with both radionuclides.
  
  
  CONCLUSIONS
  Both (124)I- and (89)Zr-labeled A11 anti-PSCA minibody showed high-contrast imaging of PSCA expression in vivo. However, the (124)I-labeled A11 minibody was found to be the superior imaging agent because of lower nonspecific uptake and higher tumor-to-soft-tissue contrast. Partial-volume correction was found to be essential for robust quantification of immunoPET imaging with both (124)I- and (89)Zr-labeled A11 minibody.
authors: Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, California.
authors: Scott M
authors: SM
authors: Knowles
authors: Kirstin A
authors: KA
authors: Zettlitz
authors: Richard
authors: R
authors: Tavaré
authors: Matthew M
authors: MM
authors: Rochefort
authors: Felix B
authors: FB
authors: Salazar
authors: David B
authors: DB
authors: Stout
authors: Paul J
authors: PJ
authors: Yazaki
authors: Robert E
authors: RE
authors: Reiter
authors: Anna M
authors: AM
authors: Wu
mesh_terms: D000818:Animals; D016477:Artifacts; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000276:immunology; D057127:Single-Chain Antibodies / Q000493:pharmacokinetics; D015040:Zirconium
chemical_list: D007457:Iodine Radioisotopes; D057127:Single-Chain Antibodies; D015040:Zirconium
keywords: 124I; 89Zr; antibody fragments; immunoPET; minibody; partial volume correction; prostate cancer; prostate stem cell antigen (PSCA)