Development of Radiogallium-Labeled Peptides for Platelet-Derived Growth Factor Receptor β (PDGFRβ) Imaging: Influence of Different Linkers

Abstract

The purpose of this study is to develop peptide-based platelet-derived growth factor receptor β (PDGFRβ) imaging probes and examine the effects of several linkers, namely un-natural amino acids (D-alanine and β-alanine) and ethylene-glycol (EG), on the properties of Ga-DOTA-(linker)-IPLPPPRRPFFK peptides. Seven radiotracers, 67Ga-DOTA-(linker)-IPLPPPRRPFFK peptides, were designed, synthesized, and evaluated. The stability and cell uptake in PDGFRβ positive peptide cells were evaluated in vitro. The biodistribution of [67Ga]Ga-DOTA-EG2-IPLPPPRRPFFK ([67Ga]27) and [67Ga]Ga-DOTA-EG4-IPLPPPRRPFFK ([67Ga]28), which were selected based on in vitro stability in murine plasma and cell uptake rates, were determined in BxPC3-luc-bearing nu/nu mice. Seven 67Ga-labeled peptides were successfully synthesized with high radiochemical yields (>85%) and purities (>99%). All evaluated radiotracers were stable in PBS (pH 7.4) at 37 °C. However, only [67Ga]27 and [67Ga]28 remained more than 75% after incubation in murine plasma at 37 °C for 1 h. [67Ga]27 exhibited the highest BxPC3-luc cell uptake among the prepared radiolabeled peptides. As regards the results of the biodistribution experiments, the tumor-to-blood ratios of [67Ga]27 and [67Ga]28 at 1 h post-injection were 2.61 ± 0.75 and 2.05 ± 0.77, respectively. Co-injection of [67Ga]27 and an excess amount of IPLPPPRRPFFK peptide as a blocking agent can significantly decrease this ratio. However, tumor accumulation was not considered sufficient. Therefore, further probe modification is required to assess tumor accumulation for in vivo imaging.

68Ga- and 211At-Labeled RGD Peptides for Radiotheranostics with Multiradionuclides

“…Cellular uptake experiments were performed according to a previous report with a slight modification . U-87 MG was cultured in Eagle’s minimum essential medium (EMEM) containing 10% fetal bovine serum (FBS) on six-well culture plates (containing 1 × 10 6 cells/well) for 24 h using a humidified atmosphere (5% CO 2 ) incubator at 37 °C.…”

RGD Peptide-Conjugated Dodecaborate with the Ga-DOTA Complex: A Preliminary Study for the Development of Theranostic Agents for Boron Neutron Capture Therapy and Its Companion Diagnostics

“…Partition coefficients of [ 67 Ga] 16 and [ 125 I] 17 into n -octanol and 0.1 M PB (pH 7.4) were determined according to previously described procedures . The partition coefficients were calculated by the ratio of cpm/mL in n -octanol to that in PB and expressed as a common logarithm (log P ).…”

Development of tumor-targeting aza-vesamicol derivatives with high affinity for sigma receptors for cancer theranostics

“…The stability experiments of [ 125 I] 15 and [ 125 I] 17 in phosphate buffer (PB) and murine plasma were performed as described previously with a slight modification. 45 Briefly, [ 125 I] 15 and [ 125 I] 17 (22–82 kBq) in 0.1 M PB pH 7.4 (100 μL) were incubated at 37 °C for 24 h. At 24 h after incubation, the purities of radiotracers were analyzed by RP-HPLC.…”