Development of Diagnostic and Therapeutic Probes with Controlled Pharmacokinetics for Use in Radiotheranostics

Ogawa, Kenji

doi:10.1248/cpb.c19-00274

Cited by 21 publications

(15 citation statements)

References 68 publications

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“…In general, the probes for radiotheranostics have been produced by the introduction of elements with similar chemical characteristics into the same precursors. 4,5 In radionuclide therapy, targeted alpha therapy (TAT) has gained much attention due to the high therapeutic effects derived from the high linear energy transfer (LET) of αparticles. 6,7 For example, a report of excellent therapeutic effects for 225 Ac-PSMA to castration-resistant prostate cancer patients was sensational.…”

Section: ■ Introductionmentioning

confidence: 99%

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

et al. 2021

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Probes for radiotheranostics could be produced by introducing radionuclides with similar chemical characteristics into the same precursors. We recently developed an 211At-labeled RGD peptide and a corresponding radioiodine-labeled RGD peptide. Both labeled peptides accumulated in large quantities in the tumor with similar biodistribution, demonstrating their usefulness for radiotheranostics. In this study, we hypothesized that probes for radiotheranostics combined with multiradionuclides, such as 68Ga and 211At, have useful clinical applications. New radiolabeled RGD peptide probes were synthesized via a molecular design approach, with two labeling sites for metal and halogen. These probes were evaluated in biodistribution experiments using tumor-bearing mice. [67Ga]Ga-DOTA-c[RGDf(4-I)K] ([67Ga]4), Ga-DOTA-[125I]c[RGDf(4-I)K] ([125I]4), and Ga-DOTA-[211At]c[RGDf(4-At)K] ([211At]7) showed similar biodistribution, with high and equivalent accumulation in tumors. These results indicate the usefulness of these probes in radiotheranostics with multiradionuclides, such as a radiometal and a radiohalogen, and they could contribute to a personalized medicine regimen.

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Section: ■ Introductionmentioning

confidence: 99%

“…Thus, developing diagnostic and therapeutic probes with equivalent biodistribution characteristics is important for a successful radiotheranostics design. In general, the probes for radiotheranostics have been produced by the introduction of elements with similar chemical characteristics into the same precursors. , …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…Targeting peptides are combined with different radionuclides, diagnostic or therapeutic isotopes, and are often used as radiotracers. The radiolabeled RGD peptide has been studied for cancer imaging and radionuclide therapy [ 22 ]. The first radiotracer developed using the RGD sequence concept, such as 18 F-Galacto-RGD, was used to diagnose head and neck squamous cell carcinoma [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Imaging and Preclinical Studies of Radiolabeled Long-Term RGD Peptides in U-87 MG Tumor-Bearing Mice

Chen

et al. 2021

IJMS

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The Arg–Gly–Asp (RGD) peptide shows a high affinity for αvβ3 integrin, which is overexpressed in new tumor blood vessels and many types of tumor cells. The radiolabeled RGD peptide has been studied for cancer imaging and radionuclide therapy. We have developed a long-term tumor-targeting peptide DOTA-EB-cRGDfK, which combines a DOTA chelator, a truncated Evans blue dye (EB), a modified linker, and cRGDfK peptide. The aim of this study was to evaluate the potential of indium-111(111In) radiolabeled DOTA-EB-cRGDfK in αvβ3 integrin-expressing tumors. The human glioblastoma cell line U-87 MG was used to determine the in vitro binding affinity of the radiolabeled peptide. The in vivo distribution of radiolabeled peptides in U-87 MG xenografts was investigated by biodistribution, nanoSPECT/CT, pharmacokinetic and excretion studies. The in vitro competition assay showed that 111In-DOTA-EB-cRGDfK had a significant binding affinity to U-87 MG cancer cells (IC50 = 71.7 nM). NanoSPECT/CT imaging showed 111In-DOTA-EB-cRGDfK has higher tumor uptake than control peptides (111In-DOTA-cRGDfK and 111In-DOTA-EB), and there is still a clear signal until 72 h after injection. The biodistribution results showed significant tumor accumulation (27.1 ± 2.7% ID/g) and the tumor to non-tumor ratio was 22.85 at 24 h after injection. In addition, the pharmacokinetics results indicated that the 111In-DOTA-EB-cRGDfK peptide has a long-term half-life (T1/2z = 77.3 h) and that the calculated absorbed dose was safe for humans. We demonstrated that radiolabeled DOTA-EB-cRGDfK may be a promising agent for glioblastoma tumor imaging and has the potential as a theranostic radiopharmaceutical.

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“…Therefore, nuclear medicine is a reasonable method for integrating theranostics. The method of using radioisotopes for theranostics is called "radiotheranostics" [3,4].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of a Dimeric RGD Peptide as a Preliminary Study for Radiotheranostics with Radiohalogens

et al. 2021

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We recently developed 125I- and 211At-labeled monomer RGD peptides using a novel radiolabeling method. Both labeled peptides showed high accumulation in the tumor and exhibited similar biodistribution, demonstrating their usefulness for radiotheranostics. This study applied the labeling method to a dimer RGD peptide with the aim of gaining higher accumulation in tumor tissues based on improved affinity with αvβ3 integrin. We synthesized an iodine-introduced dimer RGD peptide, E[c(RGDfK)] (6), and an 125/131I-labeled dimer RGD peptide, E[c(RGDfK)]{[125/131I]c[RGDf(4-I)K]} ([125/131I]6), and evaluated them as a preliminary step to the synthesis of an 211At-labeled dimer RGD peptide. The affinity of 6 for αvβ3 integrin was higher than that of a monomer RGD peptide. In the biodistribution experiment at 4 h postinjection, the accumulation of [125I]6 (4.12 ± 0.42% ID/g) in the tumor was significantly increased compared with that of 125I-labeled monomer RGD peptide (2.93 ± 0.08% ID/g). Moreover, the accumulation of [125I]6 in the tumor was greatly inhibited by co-injection of an excess RGD peptide. However, a single injection of [131I]6 (11.1 MBq) did not inhibit tumor growth in tumor-bearing mice. We expect that the labeling method for targeted alpha therapy with 211At using a dimer RGD peptide could prove useful in future clinical applications.

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Development of Diagnostic and Therapeutic Probes with Controlled Pharmacokinetics for Use in Radiotheranostics

Cited by 21 publications

References 68 publications

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

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

Molecular Imaging and Preclinical Studies of Radiolabeled Long-Term RGD Peptides in U-87 MG Tumor-Bearing Mice

Synthesis and Evaluation of a Dimeric RGD Peptide as a Preliminary Study for Radiotheranostics with Radiohalogens

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Development of Diagnostic and Therapeutic Probes with Controlled Pharmacokinetics for Use in Radiotheranostics

Cited by 21 publications

References 68 publications

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

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

Molecular Imaging and Preclinical Studies of Radiolabeled Long-Term RGD Peptides in U-87 MG Tumor-Bearing Mice

Synthesis and Evaluation of a Dimeric RGD Peptide as a Preliminary Study for Radiotheranostics with Radiohalogens

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

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