A novel [F-18] aluminum-fluoride labeled PSMA tracer with minimal background uptake

Objectives The purpose of the study is to gather preliminary biodistribution data on a new easy-to-prepare [F-18] aluminum-fluoride labeled PSMA targeting tracer. RBI1033 is a high affinity 2-5A ligand which exhibits picomolar affinity toward PSMA. We have previously demonstrated that the 2-5A nucleic acid moiety in RBI1033 can be replaced with negatively charged glutamates. We further developed it by linking an aluminum-fluoride-NOTA moiety to the PSMA targeting complex.

Methods The peptide based tracer consisting of three glutamates linked with a PSMA targeting urea moiety was synthesized using Fmoc-based solid phase peptide synthesis. A Bn-NOTA chelate was attached to a lysine residue at the end of the peptide sequence. The affinity of the unlabeled ligand was measured with a competitive binding assay using PC3-PIP cells. [F-18] labeling was performed under established conditions by incubating [F-18] NaF and a NOTA containing PSMA ligand at 106°C for 15 minutes. After HPLC purification, the labeled tracer was injected by IV into mice bearing PC3-PIP (PSMA+) xenographs. Whole body mouse PECT/CT images were obtained at 1 hour using a clinical PET/CT scanner. Preliminary biodistribution data from PSMA+ tumor bearing mice was obtained at 1 and 2 hours. We have also performed a limited biodistribution study at 4 hours in PSMA-knockout mice.

Results The unlabeled peptide ligand demonstrated an IC50 of 4.3nM. The tumor uptake was 6.9±1.4%ID/g at 1 hour and 4.6±0.6%ID/g at 2 hours. At 2 hours post injection, the tumor:bone ratio was 46:1; tumor:blood ratio was 115:1 and tumor:liver ratio was 27:1. At 4 hours post injection, in PSMA-knockout mice, the highest residual uptake was in the kidney with 1.6±0.5%ID/g. The second highest uptake was seen in bone and small intestine, which both measured 0.05%ID/g.

Conclusions The [F-18] Al-F labeled PSMA targeting tracer derived from RBI1033 demonstrated promising tumor targeting with excellent tumor : background ratio.

Research Support Department of Defense: W81XWH-10-1-0218