(124)I-L19-SIP for immuno-PET imaging of tumour vasculature and guidance of (131)I-L19-SIP radioimmunotherapy.
OBJECTIVE
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.
Tijink
Bernard M
BM
Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, De Boelelaan 1117, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
Perk
Lars R
LR
Budde
Marianne
M
Stigter-van Walsum
Marijke
M
Visser
Gerard W M
GW
Kloet
Reina W
RW
Dinkelborg
Ludger M
LM
Leemans
C René
CR
Neri
Dario
D
van Dongen
Guus A M S
GA
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005240:Feasibility Studies; D006801:Humans; D007267:Injections; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007553:Isotope Labeling; D051379:Mice; D009367:Neoplasm Staging; D009369:Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000276:immunology / Q000532:radiotherapy*; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging* / Q000276:immunology; D049268:Positron-Emission Tomography / Q000379:methods*; D016499:Radioimmunotherapy / Q000379:methods*; D011880:Radiotherapy Planning, Computer-Assisted; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014508:Urea / Q000031:analogs & derivatives / Q000737:chemistry
D000906:Antibodies; D007457:Iodine Radioisotopes; D011993:Recombinant Fusion Proteins; C513931:SIP(L19) fusion protein; C012385:1,3,4,6-tetrachloro-3 alpha,6 alpha-diphenylglycoluril; D014508:Urea