Introduction:

Neuroendocrine-differentiated prostate cancer (NEPC) is an aggressive and treatment-resistant subtype of prostate cancer that often emerges as a mechanism of resistance to androgen deprivation therapy (ADT). Unlike conventional prostate adenocarcinoma, NEPC expresses high levels of somatostatin receptor 2 (SSTR2) and often retains some prostate-specific membrane antigen (PSMA) expression, making these two receptors promising theranostic targets.

Dual-targeting radiopharmaceuticals designed for both PSMA and SSTR2 can enhance imaging sensitivity and therapeutic efficacy, addressing tumor heterogeneity in NEPC.

Conclusion:

PSMA and SSTR2 dual-targeting theranostics represent a promising strategy for diagnosing and treating NEPC, a highly aggressive prostate cancer subtype. By leveraging both molecular targets, these agents have the potential to improve patient outcomes, extend survival, and personalize treatment for those with advanced or treatment-resistant disease.

First in Class

[⁶⁸Ga]Ga/[¹⁷⁷Lu]Lu-DOTA-NI-FAPI-04: A Novel Theranostic Agent

Introduction:

[⁶⁸Ga]Ga/[¹⁷⁷Lu]Lu-DOTA-NI-FAPI-04 is a next-generation theranostic radiopharmaceutical designed for both imaging and targeted radioligand therapy (RLT) in solid tumors. It combines:

• Fibroblast Activation Protein Inhibitor (FAPI) for targeting cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME).
• Nitroimidazole (NI) Moiety for hypoxia targeting, improving retention in hypoxic tumor regions.

By incorporating both FAPI and NI functionalities, DOTA-NI-FAPI-04 enhances tumor localization, uptake, and therapeutic efficacy, making it a promising agent for theranostics.

Conclusion:

[⁶⁸Ga]Ga/[¹⁷⁷Lu]Lu-DOTA-NI-FAPI-04 represents a promising next-generation theranostic agent, offering dual-targeting of hypoxia and tumor stroma. By integrating FAPI’s tumor-stroma specificity with NI’s hypoxia selectivity, this radiopharmaceutical could revolutionize cancer imaging and therapy, particularly for radioresistant, PSMA-negative, or hypoxic tumors.

First in Class

⁶⁸Ga/¹⁷⁷Lu-Labeled Bivalent Agents for Targeting Hypoxia and PSMA in Prostate Cancer

Introduction:

Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) has revolutionized metastatic castration-resistant prostate cancer (mCRPC) treatment. However, tumor hypoxia—a key factor in radioresistance—remains a major challenge. Bivalent agents labeled with ⁶⁸Ga (imaging) and ¹⁷⁷Lu (therapy) that target both PSMA and hypoxia offer an innovative approach to enhance tumor uptake and therapeutic response.

Conclusion:

⁶⁸Ga/¹⁷⁷Lu-Labeled Bivalent Agents for Hypoxia and PSMA in Prostate Cancer offer a novel dual-targeting strategy to improve detection and treatment outcomes, particularly for radioresistant and PSMA-negative tumors. By combining PSMA specificity with hypoxia retention, these agents enhance tumor uptake, prolong retention, and increase therapeutic efficacy, representing a next-generation approach for precision radiotheranostics in prostate cancer.

Introduction:

• Bone metastases are a significant clinical challenge in advanced cancers, especially in prostate and breast cancer. Bisphosphonates (BPs) are widely used for treating bone disorders due to their high affinity for hydroxyapatite (HA) in bone tissue. [⁶⁸Ga]Ga/[¹⁷⁷Lu]Lu-DOTA-HBED-bisphosphonate represents a next-generation theranostic agent designed for both imaging and radionuclide therapy (RNT) of bone metastases.
• This dual-labeled radiopharmaceutical consists of a bisphosphonate moiety for high-affinity binding to hydroxyapatite in bone lesions, two chelators for radiometal incorporation, and either ⁶⁸Ga for PET imaging or ¹⁷⁷Lu for therapeutic applications.
• [¹⁷⁷Lu]Lu-P15-073 shows great potential in treating patients with metastatic cancers involving bone, particularly in advanced prostate cancer. Bone metastasis is a common complication in prostate cancer, leading to severe pain, fractures, and diminished quality of life. Traditional treatments, such as chemotherapy and external radiation, often fail to provide sufficient efficacy in these cases and may lead to significant side effects.

Conclution：

• Given its targeted mechanism of action and ability to deliver high-dose radiation to osteoblastic lesions, [¹⁷⁷Lu]Lu-P15-073 offers an exciting therapeutic option for advanced prostate cancer patients, especially those with bone metastases.
• [⁶⁸Ga]Ga/[¹⁷⁷Lu]Lu-DOTA-HBED-Bisphosphonate is a promising theranostic agent for diagnosing and treating bone metastases. With high selectivity, strong retention, and effective β-emission therapy, it represents a next-generation approach to bone-targeted radiopharmaceuticals.