PET imaging of prostate tumors with ¹⁸F‐Al‐NOTA‐MATBBN

Abstract

Overexpression of the gastrin-releasing peptide receptor (GRPR) in prostate cancer provides a promising target for detection the disease. MATBBN is a new bombesin analog originating from the GRPR antagonists with a hydrophilic linker. In this study NOTA-conjugated MATBBN was labeled by the Al(18)F method and the potential of (18)F-Al-NOTA-MATBBN for prostate tumor PET imaging was also evaluated. NOTA-MATBBN was radiolabeled with (18) F using Al(18)F complexes. Partition coefficient, in vitro stability and GRPR binding affinity were also determined. PET studies were performed with (18)F-Al-NOTA-MATBBN in PC-3 tumor-bearing mice. (18)F-Al-NOTA-MATBBN can be produced within 30 min with a decay-corrected yield of 62.5 ± 2.1% and a radiochemical purity of >98%. The logP octanol-water value for the Al(18)F-labeled BBN analog was -2.40 ± 0.07 and the radiotracer was stable in phosphate-buffered saline and human serum for 2 h. The IC50 values of displacement for the (18)F-Al-NOTA-MATBBN with MATBBN was 126.9 ± 2.75 nm. The PC-3 tumors were clearly visible with high contrast after injection of the labeled peptide. At 60 min post-injection, the tumor uptakes for (18)F-Al-NOTA-MATBBN and (18)F-FDG were 4.59 ± 0.43 and 1.98 ± 0.35% injected dose/g, and tumor to muscle uptake radios for two tracers were 6.77 ± 1.10 and 1.78 ± 0.32, respectively. Dynamic PET revealed that (18) F-Al-NOTA-MATBBN was excreted mainly through the kidneys. GRPR-binding specificity was also demonstrated by reduced tumor uptake of (18)F-Al-NOTA-MATBBN after coinjection with excess unlabeled MATBBN peptide at 1 h post-injection. NOTA- MATBBN could be labeled rapidly with (18)F using one step method. (18)F-Al-NOTA-MATBBN may be a promising PET imaging agent for prostate cancer.

PET of HER2 Expression with a Novel 18FAl Labeled Affibody

“…21 It may limit the potential for clinical application since the liver is a common metastatic site of cancer. A novel hydrophilic linker, Gly-Gly-Gly-Arg-Asp-Asn, significantly decreased the abdominal background at early time (nearly 30min) postinjection and efficiently improved the imaging qualities 24,25,26. Thus, we hypothesized that a modified cysteinylated ZHER 2:342 affibody with the linker, denoted as MZHER 2:342 , might possess more favorable in vivo pharmacokinetic performances.…”

Gastrin-releasing peptide receptor-targeted gadolinium oxide-based multifunctional nanoparticles for dual magnetic resonance/fluorescent molecular imaging of prostate cancer

“…This was attributed to the fact that BBN can remarkably enhance NPs uptake through GRPR-mediated endocytosis. 21 Moreover, fluorescence microscopy images showed that Gd 2 O 3 -FI-PEG-BBN fluorescence was predominantly accumulated in the cytoplasm around the nucleus.…”

An investigation on the anti-tumor properties of FSH33-53-Lytic

“…10 min static PET scans were acquired at 30 min, 1, and 2 h after injection. Analytic methods of image were according to the study of Xu, Pan, et al [26,28]. The images were reconstructed using a three-dimensional ordered subset expectation maximum (OSEM) algorithm, and no correction was applied for attenuation or scatter.…”