(124)I-L19-SIP for immuno-PET imaging of tumour vasculature and guidance of (131)I-L19-SIP radioimmunotherapy

Eur J Nucl Med Mol Imaging. 2009 Aug;36(8):1235-44. doi: 10.1007/s00259-009-1096-y. Epub 2009 Mar 4.


Purpose: The human monoclonal antibody (MAb) fragment L19-SIP is directed against extra domain B (ED-B) of fibronectin, a marker of tumour angiogenesis. A clinical radioimmunotherapy (RIT) trial with (131)I-L19-SIP was recently started. In the present study, after GMP production of (124)I and efficient production of (124)I-L19-SIP, we aimed to demonstrate the suitability of (124)I-L19-SIP immuno-PET for imaging of angiogenesis at early-stage tumour development and as a scouting procedure prior to clinical (131)I-L19-SIP RIT.

Methods: (124)I was produced in a GMP compliant way via (124)Te(p,n)(124)I reaction and using a TERIMO module for radioiodine separation. L19-SIP was radioiodinated by using a modified version of the IODO-GEN method. The biodistribution of coinjected (124)I- and (131)I-L19-SIP was compared in FaDu xenograft-bearing nude mice, while (124)I PET images were obtained from mice with tumours of <50 to approximately 700 mm(3).

Results: (124)I was produced highly pure with an average yield of 15.4 +/- 0.5 MBq/microAh, while separation yield was approximately 90% efficient with <0.5% loss of TeO(2). Overall labelling efficiency, radiochemical purity and immunoreactive fraction were for (124)I-L19-SIP: approximately 80 , 99.9 and >90%, respectively. Tumour uptake was 7.3 +/- 2.1, 10.8 +/- 1.5, 7.8 +/- 1.4, 5.3 +/- 0.6 and 3.1 +/- 0.4%ID/g at 3, 6, 24, 48 and 72 h p.i., resulting in increased tumour to blood ratios ranging from 6.0 at 24 h to 45.9 at 72 h p.i.. Fully concordant labelling and biodistribution results were obtained with (124)I- and (131)I-L19-SIP. Immuno-PET with (124)I-L19-SIP using a high-resolution research tomograph PET scanner revealed clear delineation of the tumours as small as 50 mm(3) and no adverse uptake in other organs.

Conclusions: (124)I-MAb conjugates for clinical immuno-PET can be efficiently produced. Immuno-PET with (124)I-L19-SIP appeared qualified for sensitive imaging of tumour neovasculature and for predicting (131)I-L19-SIP biodistribution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / administration & dosage
  • Antibodies / chemistry
  • Antibodies / therapeutic use*
  • Cell Line, Tumor
  • Feasibility Studies
  • Humans
  • Injections
  • Iodine Radioisotopes* / pharmacokinetics
  • Isotope Labeling
  • Mice
  • Neoplasm Staging
  • Neoplasms / blood supply*
  • Neoplasms / diagnostic imaging
  • Neoplasms / immunology
  • Neoplasms / radiotherapy*
  • Neovascularization, Pathologic / diagnostic imaging*
  • Neovascularization, Pathologic / immunology
  • Positron-Emission Tomography / methods*
  • Radioimmunotherapy / methods*
  • Radiotherapy Planning, Computer-Assisted
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / pharmacokinetics
  • Recombinant Fusion Proteins / therapeutic use*
  • Tissue Distribution
  • Transplantation, Heterologous
  • Urea / analogs & derivatives
  • Urea / chemistry


  • Antibodies
  • Iodine Radioisotopes
  • Recombinant Fusion Proteins
  • SIP(L19) fusion protein
  • 1,3,4,6-tetrachloro-3 alpha,6 alpha-diphenylglycoluril
  • Urea