Investigation of SP94 Peptide as a Specific Probe for Hepatocellular Carcinoma Imaging and Therapy

Abstract

SP94 (SFSIIHTPILPL), a novel peptide, has shown specific binding to hepatocellular carcinoma (HCC) cells. We aimed to investigate the capability of SP94 as a targeting probe for HCC imaging and therapy following labeling with technetium-99m (99mTc) and rhenium-188 (188Re). HYNIC-SP94 was prepared by solid phase synthesis and then labeled with 99mTc. Cell competitive binding, internalization assay, in vitro and in vivo stability, biodistribution and micro-single photon emission computed tomography /computed tomography (SPECT/CT) imaging studies were performed to investigate the capability of 99mTc tricine-EDDA/HYNIC-SP94 as a specific HCC imaging probe. Initial promising targeting results inspired evaluation of its therapeutic effect when labeled by 188Re. HYNIC-SP94 was then labeled again with 188Re to perform cell apoptosis, microSPECT/CT imaging evaluation and immunohistochemistry. Huh-7 cells exhibited typical apoptotic changes after 188Re irradiation. According to 99mTc tricine-EDDA/HYNIC-SP94 microSPECT/CT imaging, tumor uptake was significantly decreased compared with that of pre-treatment with 188Re-HYNIC-SP94. The immunohistochemistry also displayed obvious necrosis and apoptosis as well as inhibition of proliferation in the 188Re-HYNIC-SP94 treatment group. The results supported that 99mTc tricine-EDDA/HYNIC-SP94 is able to target HCC cells and 188Re-HYNIC- SP94 holds potential as a therapeutic agent for HCC, making 99mTc/188Re-HYNIC-SP94 a promising targeting probe for HCC imaging and therapy.

Evaluation of EGFR-TK Expression with a 99mTc-Labeled Complex Bearing Quinazoline Pharmacophore

“…6,19 The tailored drugs have smaller size, which offer many advantages in molecule imaging, for example, more favorable pharmacokinetics, better tissue penetration, and more preferable flexibility in chemical modification. 25,29 To date, several EGFR-targeted probes have been reported in evaluating the EGFR expression, such as the carbon-11, fluorine-18, or iodine-125-labeled anilinoquinazoline derivatives, which have shown promise in imaging EGFR expression level in nonsmall cell lung carcinoma (NSCLC) patients. 9,22,30 Whereas the use of 11 radionuclides in clinical trials have been hampered to a certain extent because of their short half-life, which require an on-site cyclotron for production, and repeated fabrication (especially 11 C) when several subjects need to be examined, the 125 I has a long half-life that would promote accumulation radiation dosimetry.…”

“…The resulting chelate usually has poor in vivo and in vitro stability. 25 Here, the authors used the N-hydroxysuccinimidyl Sacetylmercaptoacetyltriglyglycinate (NHS-MAG 3 ) as a bifunctional chelator that is easily synthesized and conjugated. The conjugation product was easily radiolabeled with 99m Tc, and the radiolabeled probes have shown stability suitable for diagnosis and therapeutic application in the laboratory.…”

99mTc‐HYNIC‐(Ser)3‐J18 peptide: A radiotracer for non‐small‐cell lung cancer targeting

“…[6] Here, we report of a peptide (J18) labeled with 99m Tc for NSCLS targeting. [11,18] Various pharmacokinetic modifying linkers have been applied for improvement of the excretion kinetics and hydrophilicity of radiolabeled peptides. It exhibited a good tumor targeting in SKOV-3 xenografts in mice.…”

Recent advances in hepatocellular carcinoma therapy

“…SP94, a synthetic peptide has been reported to show specific activity for targeted delivery against HCC (Li et al, 2016). Lo et al reported the use of SP94 through the use of phage displayed random peptide library both in vitro and in vivo in HCC.…”