The utility of radiolabeled PSMA ligands for tumor imaging.

Prostate-specific membrane antigen (PSMA) is a glycosylated type-II transmembrane protein expressed in prostatic tissue and significantly overexpressed in several prostate cancer cells. Despite its name, PSMA has also been reported to be overexpressed in endothelial cells of benign and malignant non-prostate disease. So its clinical use was extended to detection, staging, and therapy of various tumor types. Recently small molecules targeting PSMA have been developed as imaging probes for diagnosis of several malignancies. Preliminary studies are emerging improved diagnostic sensitivity and specificity of PSMA imaging, leading to a change in patient management. In this review, we evaluated the first preclinical and clinical studies on PSMA ligands resulting future perspectives radiolabeled PSMA in staging and molecular characterization, based on histopathologic examinations of PSMA expression.

Preparation and evaluation of 99m Tc-HYNIC-D (TPPE) as a new targeted imaging probe for detection of colon cancer: Preclinical comparison with 99m Tc-HYNIC-EPPT.

The aim of this study was to prepare radiolabeled peptide-based agents for imaging of colon cancer. According to the incorporation of HYNIC for radiolabeling with technetium-99m, two analogs were designed and compared: an antitumor-antibody-derived peptide based on the EPPT sequence and a novel retro-inverso peptidomimetic derivative D (TPPE) structurally modified by replacing the L-amino acids with D-amino acids and reversing the primary amino acid sequence of EPPT. The HYNIC-conjugated peptides were labeled with 99m Tc using tricine/EDDA coligand with more than 98% radiochemical yield and showed high metabolic stability. Kd values of 41.77 ± 7.34 nM and 37.33 ± 8.37 nM for 99m Tc-HYNIC-EPPT and 99m Tc-HYNIC-D (TPPE) confirmed high affinity of both peptides for cell surface antigen MUC1. These radiotracers demonstrated no significant differences in the cellular uptake and internalization value, but the biodistribution profile of 99m Tc-HYNIC-D (TPPE) was more favorable than that of 99m Tc-HYNIC-EPPT as a result of better tumor-to-non-target ratios for the examined tissues and organs. HT29 tumors were visualized more clearly in scintigraphic images with 99m Tc-HYNIC-D (TPPE) in comparison with 99m Tc-HYNIC-EPPT. The results showed the retro-inverso analog to be a more promising radiotracer as a probe for in vivo targeting of HT-29 tumors than the parent peptide.

In vitro/in vivo assessment of the targeting ability of [99mTc] Tc-labeled an aptide specific to the extra domain B of fibronectin (APTEDB) for colorectal cancer.

OBJECTIVE: The APTEDB is an aptide specific to the extra domain B (EDB) of fibronectin with high affinity for EDB, which is expressed in malignant tumors including brain cancer (U87MG) and colorectal cancer (HT-29). Aim of this study was to evaluate the [99mTc] Tc-APTEDB potential as an imaging probe for colorectal cancer. METHODS: Radiochemical purity was evaluated by HPLC and radio-isotope TLC scanner. Blocking study for specific binding assay and affinity calculation (Kd) on HT-29 cell lines were also carried out. Planar imaging and bio-distribution studies were performed in HT-29 tumor-bearing mice. RESULTS: The APTEDB was efficiently labeled with technetium-99m in high radiochemical yield (up to 97%). Cellular binding study demonstrated specific binding of the [99mTc] Tc-APTEDB in cultured HT-29 cells. The Kd value was found to be 40.46 ± 13.39 nM. The tumor-to-muscle ratio was ~ 1.5 in ex vivo bio-distribution study at 1 h after injection. Planar imaging study showed higher activity accumulation in EDB expressing HT-29 tumor relative to muscle (used as control) (~ 1.7) at 1 h. CONCLUSIONS: Although more studies are required to find out the full potential of this radio-ligand as an imaging probe, the present results nevertheless provide useful information about [99mTc] Tc-APTEDB, which might be beneficial in design and development of new [99mTc] Tc-APTEDB for efficient targeting of tumor in vivo.

99m Tc-(EDDA/tricine)-HYNIC-GnRH analogue as a potential imaging probe for diagnosis of prostate cancer.

Prostate cancer is a serious threat to men's health, so it is necessary to develop the techniques for early detection of this malignancy. Radiolabeled peptides are the useful tools for diagnosis of prostate cancer. In this research, we designed a new HYNIC-conjugated GnRH analogue and labeled it by 99m Tc with tricine/EDDA as coligands. We used aminohexanoic acid (Ahx) as a hydrocarbon linker to generate 99m Tc-(tricine/EDDA)-HYNIC-Ahx-[DLys6 ]GnRH. The radiopeptide exhibited high radiochemical purity and stability in solution and serum. Two human prostate cancer cell lines LN-CaP and DU-145 were used for cellular experiments. The binding specificity and affinity of radiopeptide for LN-CaP were superior to DU-145 cells. The Kd values for LN-CaP and DU-145 cells were 41.91 ± 7.03 nM and 55.96 ± 10.56 nM, respectively. High kidney uptake proved that the main excretion route of radiopeptide was through the urinary system. The tumor/muscle ratio of 99m Tc-HYNIC-Ahx-[DLys6 ]GnRH was 4.14 at 1 hr p.i. that decreased to 2.41 at 4 hr p.i. in LN-CaP tumor-xenografted nude mice. The blocking experiment revealed that the tumor uptake was receptor-mediated. The lesion was visualized clearly using 99m Tc-[DLys6 ]GnRH at 1 hr p.i. Accordingly, this research highlights the capability of 99m Tc-(tricine/EDDA)-HYNIC-Ahx-[DLys6 ]GnRH peptide as a promising agent for GnRHR-expressing tumor imaging.