RT Journal Article SR Electronic T1 Residualizing Iodine Markedly Improved Tumor Targeting Using Bispecific Antibody-Based Pretargeting JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1016 OP 1022 VO 46 IS 6 A1 Frank G. van Schaijk A1 Matthias Broekema A1 Egbert Oosterwijk A1 Juliette E.M. van Eerd A1 Bill J. McBride A1 David M. Goldenberg A1 Frans H.M. Corstens A1 Otto C. Boerman YR 2005 UL http://jnm.snmjournals.org/content/46/6/1016.abstract AB Previous studies have shown that pretargeting allows rapid visualization of renal cell carcinomas (RCC) with an 111In-labeled bivalent peptide. For radioimmunotherapy, a β-emitting radionuclide labeled to a bivalent peptide is required. Therapeutic efficacy of these radionuclides depends on the Emax, physical half-life, and residence time of the radiolabel in the tumor. The 131I radiolabel generally clears rapidly from the tumor after internalization and subsequent degradation of the bivalent l-amino acid peptide (l-a.a. peptide) in the tumor cells. To improve the residence time of the iodine label in the tumor, a new bivalent peptide was synthesized that is peptidase resistant and consists of 4 d-amino acids (d-a.a. peptide). Here we investigated the characteristics of the residualizing iodine label in SK-RC-52 RCC tumors. Methods: The d-a.a. peptide was manually synthesized according to standard solid-phase Fmoc/HBTU (2-[1H-benzotriazole-1-yl]-1,1,3,3-tetramethyluronium hexafluorophosphate) chemistry. The uptake and retention in the tumor of 111In-/125I-labeled bivalent peptides (l-a.a. peptide and d-a.a. peptide) were studied in female BALB/c athymic mice with subcutaneous SK-RC-52 RCC tumors. Tumors were pretargeted with the bispecific monoclonal antibody (bs-mAb) G250xDTIn-1 and, 72 h later, mice were injected intravenously with one of both radiolabeled peptides. The effect of bs-mAb—diDTPA—bs-mAb (DTPA is diethylenetriaminepentaacetic acid) bridging at the tumor cell surface on the internalization of the bs-mAb—diDTPA complex was investigated in SK-RC-52 tumor-bearing mice. Results: The maximum uptake and retention of 125I-labeled l-a.a. peptide in the tumor were significantly lower compared with that of the 111In-labeled l-a.a. peptide. In contrast, the tumor uptake and retention of the 125I-labeled d-a.a. peptide) were similar to that of the 111In-labeled l-a.a. peptide but were superior at later time points. The biodistribution of the radioiodinated d-a.a. peptide was highly similar to that of the 111In-labeled d-a.a. peptide, and both radiolabeled peptides were retained significantly better in the tumor than the 111In-labeled l-a.a. peptide. bs-mAb—diDTPA—bs-mAb bridge formation did not affect internalization of the bs-mAb—diDTPA complex. Conclusion: Uptake and retention in the tumor of the iodinated peptide after pretargeting with a bs-mAb can be significantly improved using d-a.a. peptides. Accordingly, the radiation dose to the tumor, correlating with the therapeutic efficacy of pretargeted RCC, can be enhanced substantially.