PSMA I&T - Radioligand

PSMA I&T is a theranostic small-molecule ligand composed of a Glu-urea-Lys pharmacophore and a DOTAGA chelator. The pharmacophore binds with high affinity to the prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein strongly overexpressed on prostate cancer cells, and inhibits it. When the chelator is labeled with radionuclides (e.g., Ga-68, Lu-177, Ac-225), PSMA I&T becomes a radioligand that enables PET/CT imaging and peptide receptor radionuclide therapy (PRRT) of prostate cancer. This dual diagnostic and therapeutic application makes PSMA I&T a valuable agent in oncology.

Produced by JPT Peptide Technologies, a leader in custom peptide synthesis and oncology research reagents.

PSMA I&T - Radioligand, precursor for radiolabeled PSMA-I&T and with high affinity for the prostate-specific membrane antigen (PSMA). Can be bound to radionuclides for development of cancer treatment and diagnosis. For research use only!

PSMA I&T - Radioligand - Specifications

• Peptide sequence: (R)-DOTAGA-D-Tyr(3-I)-D-Phe-D-Lys[Sub-Lys-CO-Glu]--OH
• Amount: 2 mg (20 x100µg)
• Purity: >95% (HPLC-MS)
• Delivery Format: Freeze-dried in glass vial
• CAS: 2192281-54-0
• Application(s): Nuclear medicine
• Condition(s)/Topic(s): Cancer
• Standard Delivery Time: approx. 3 weeks

Radiolabeled PSMA-I&T (Zadavotide guraxetan) variants and their applications:

PSMA-I&T is a non-radioactive precursor that can be labeled with different radionuclides via its DOTAGA chelator and generate radioligands essential for diagnosing and treating prostate cancer.

• An established diagnostic variant is [^68Ga]Ga-PSMA-I&T, where Gallium-68 emits positrons (β+), enabling high-resolution PET/CT imaging of prostate cancer lesions.
• For therapeutic applications, [^177Lu]Lu-PSMA-I&T is widely used in peptide receptor radionuclide therapy (PRRT), in which Lutetium-177 emits B- particles that deliver cytotoxic radiation to PSMA-expressing tumor cells, while its accompanying low-energy gamma photons also allow SPECT imaging and dosimetry.
• An alternative therapeutic approach employs [^225Ac]Ac-PSMA-I&T, in which Actinium-225 releases highly energetic a-particles with short tissue penetration, resulting in potent tumor cell killing even in small metastatic deposits.

Collectively, these variants highlight the versatility of PSMA I&T as a platform for both diagnosis and targeted radionuclide therapy in prostate cancer.

We also offer customized PSMA-I&T Peptide tailored to your research needs (non-radioactive variants). More information is available on our website

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Are you interested in other peptides? Choose your sequence, amount and purity. We will assist you along the way. Visit our Custom Peptide Synthesis.
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Research areas and applications of Zadavotide guraxetan, CAS: 2192281-54-0:

• Prostate cancer imaging research: Applied as a tracer for detecting primary tumors, lymph node metastases, and distant disease using PET/CT or SPECT/CT imaging.
• Radionuclide therapy studies: Extensively studied in its [^177Lu]Lu- and [^225Ac]Ac-PSMA-I&T forms for peptide receptor radionuclide therapy (PRRT) of advanced prostate cancer.
• Theranostic framework research: Serves as both the diagnostic and therapeutic agent within a single molecular platform, enabling personalized treatment approaches.
• Early detection and staging studies: Applied in research to identify prostate cancer at early stages and to assess disease spread with PET/CT or SPECT.
• Tumor recurrence investigations: Used to localize recurrent prostate cancer, even at low PSA levels, to support timely clinical decisions.
• Dosimetry and tumor heterogeneity studies: Enables radiation dose monitoring, while also assessing variations in PSMA expression across lesions to guide therapeutic strategies.
• Comparative tracer research: Studied alongside other PSMA ligands (e.g., PSMA-11, PSMA-617) to assess differences in affinity, pharmacokinetics, and clinical performance.
• Exploration in non-prostatic PSMA-expressing diseases: Investigated in preclinical and exploratory studies of cancers with PSMA expression, such as triple-negative breast cancer, glioblastoma and renal cell carcinoma.
• Pharmacokinetic and biodistribution studies: Researched to understand how it is cleared from the body, which organs it accumulates in (especially salivary glands and kidneys), and how effectively it targets prostate cancer tumors.

Benefits of PSMA-I&T (Zadavotide guraxetan):

• High affinity for PSMA: Selectively targets prostate cancer cells with strong binding efficiency.
• Stable radiolabeling: The DOTAGA chelator ensures reliable and stable labeling with radionuclides.
• Versatile chelation: Enables versatile radiolabeling with various radionuclides/isotopes (e.g., Ga-68, Lu-177, Ac-225, Cu-64).
• Theranostic ability: Combines imaging and therapy in a single platform, supporting both PET/CT diagnosis and peptide receptor radionuclide therapy (PRRT).
• Favorable pharmacokinetics: Provides high tumor uptake, sustained retention, and efficient clearance from non-target tissues.
• Proven performance: Demonstrated efficacy and safety in numerous clinical studies as a reliable theranostic agent.

Key Concepts

What is a DOTA/DOTAGA chelator?

• DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) is a macrocyclic octadentate chelator with four acetic acid arms that provide eight coordination sites for binding metal ions, forming stable complexes with radionuclides such as Ga3+, Lu3+, and In3+.
• DOTAGA (1,4,7,10-tetraazacyclododecane-1,4,7-tris(acetic acid)-10-(glutaric acid)) is a derivative where one acetic acid arm is replaced by a glutaric acid side chain, preserving octadentate coordination while adding a reactive carboxyl group for efficient conjugation to peptides, antibodies, or small-molecule ligands.
  • Compared to DOTA, DOTAGA is more hydrophilic and often shows improved affinity for molecular targets, leading to greater internalization and tumor accumulation. As a bifunctional chelator, it forms highly stable, kinetically inert complexes that prevent radionuclide dissociation under physiological conditions.
  • Consequently, DOTAGA is widely applied in theranostic radiopharmaceuticals such as PSMA I&T, enabling stable radiolabeling with isotopes like Ga-68, Lu-177, and Ac-225 while linking the chelator to the targeting pharmacophore.

What is a pharmacophore?

In medicinal chemistry, a pharmacophore refers to the minimal arrangement of structural features within a molecule that is necessary for recognition and interaction with a biological target.

In Zadavotide guraxetan, this role is fulfilled by the Glu-urea-Lys binding motif, designed to imitate natural glutamate-containing substrates of the prostate-specific membrane antigen (PSMA, also called glutamate carboxypeptidase II).

• PSMA normally cleaves terminal glutamate residues, but the central urea bond linked to the glutamate residue in this motif cannot be hydrolyzed, making PSMA I&T a potent inhibitor that locks into the enzyme’s active site. This inhibitory interaction provides high affinity and specificity for PSMA-expressing tumor cells, ensuring selective targeting.
• The lysine residue serves as a linker, enabling conjugation of the pharmacophore to the DOTAGA chelator, which allows stable radiolabeling with diagnostic and therapeutic radionuclides.

What are radionuclides and radioligands?

Radionuclides are unstable isotopes of elements that release radiation during their decay, such as gamma photons, beta particles, or alpha particles. These emissions can be detected with imaging technologies or used for delivering cytotoxic radiation directly to diseased tissue in therapeutic applications.

Radioligands are compounds composed of a targeting ligand, which binds selectively to a biological structure such as a receptor or enzyme, and a radionuclide, which provides the radioactive signal. This design combines the specificity of the ligand with the detectability or therapeutic power of the radionuclide. Consequently, radioligands can be applied both in diagnostic imaging (e.g., PET or SPECT scans) and in targeted radionuclide therapy, establishing them as essential tools in oncology.

What is Peptide Receptor Radionuclide Therapy?

Peptide Receptor Radionuclide Therapy (PRRT) is a targeted cancer treatment that combines a small peptide, designed to bind specifically to receptors overexpressed on tumor cells, with a therapeutic radionuclide (e.g., Lu-177) labeled to a stabilizing chelator.

When the peptide binds to its receptor (such as PSMA on prostate cancer cells), the radionuclide attached delivers localized radiation directly into the cancer cell. This selective delivery maximizes tumor cell damage while sparing surrounding healthy tissue. Through this receptor-targeted mechanism, PRRT facilitates tumor regression and disease stabilization, and has emerged as an effective therapeutic option for patients with advanced, or metastatic conditions.

JPT’s Oncology Peptides

One focus of JPT’s product development is oncology. Therefore, we offer a huge variety of TAA peptide, peptide pools and microarrays, as well as <DOTA peptides and radio sensitizers. JPT Peptide Technologies has substantial, long-standing expertise in providing peptides in all formats, scales and modifications to the global scientific community. All our catalog peptides are provided with HPLC-MS analyses to confirm the identity and demonstrate the high quality of our peptides.
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