SSTR2 positive

Both, AdFITC(E2)-CAR T-cell tumor infiltration and biocidal activity were Octo-Fluo concentration-dependent, with high doses of Octo-Fluo, saturating both the CAR and the SSTR2 antigen independently, leading to the loss of tumor infiltration and biocidal activity due to the loss of bridge formation. Our findings demonstrate the potential of using AdFITC(E2)-CAR T-cells with Octo-Fluo as a versatile, on-off tunable bispecific adaptor for targeted CAR T-cell immunotherapy against SSTR2-positive NETs.

Beyond that, copper‑64- and copper‑61-labeled versions offer possibilities for pre- and post-therapeutic PET. Therefore, NODAGA-cLAB4-TATE has the potential to advance clinical use of radiocopper in SSTR2-targeted cancer theranostics.

P2, N=618, Active, not recruiting, Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori | Unknown status --> Active, not recruiting | Trial completion date: May 2021 --> Jan 2025 | Trial primary completion date: May 2021 --> Jan 2025

A 52-year-old woman was diagnosed with Graves' disease 26 years ago and stopped going to the hospital after several years of treatment with thiamazole...She was treated for breast cancer with trastuzumab deruxtecan therapy and for TSH-PitNET with lanreotide...Recently, SSTR2 and IGF-1R were reported to be expressed in breast cancer, and several clinical trials of SSAs for breast cancer have been conducted. SSAs are effective in improving pituitary and thyroid functions against TSH-PiTNET, and in combination with chemotherapy, they may have synergistic antitumor effects in patients with SSTR2-positive breast cancer.

The successful synthesis and coupling of the trifunctional chelate to the peptide and fluorescent dye support the potential of this synthetic approach to generate dual labeled tracers. While promising in vitro, the in vivo results obtained with [111In]In-eTFC-01 suggest the need for adjustments to enhance tracer distribution.

P2, N=20, Recruiting, Jules Bordet Institute | Trial completion date: Sep 2023 --> Jun 2024 | Trial primary completion date: Sep 2023 --> Jun 2024

The antitumor efficacy of [67Cu]Cu-EB-TATE is comparable to that of [177Lu]Lu-EB-TATE, with [67Cu]Cu-EB-TATE being slightly more effective than [177Lu]Lu-EB-TATE for complete remission of small tumors. [67Cu]Cu-EB-TATE therefore warrants clinical development.

P4, N=200, Recruiting, Weill Medical College of Cornell University | Phase classification: P=N/A --> P4

Imaging and biodistribution analysis showed preferential accumulation of the PDC in receptor-positive tumors and high renal clearance. This study identified a trackable SSTR2-targeting system for TMZ delivery and utilizes a modular design that could be broadly applied in PDC development.

Ga-FAPI-LM3 exhibited FAPI and SSTR2 dual-receptor-targeting properties both in vitro and in vivo, resulting in improved tumor uptake and retention compared with that observed with monomeric Ga-FAPI and Ga-DOTA-LM3. This study highlights the clinical feasibility of Ga-FAPI-LM3 PET/CT for NPC imaging.

P1/2, N=52, Recruiting, Viewpoint Molecular Targeting | Not yet recruiting --> Recruiting

She was treated with radical radiotherapy, but her plasma Epstein-Barr virus DNA load continued to increase despite good locoregional response. As her primary tumor was positive for somatostatin receptor type 2, we performed 68Ga-DOTATATE PET/CT, which revealed multiple DOTATATE-avid distant metastases.

Surprisingly, we found that [At]SAB-Oct could up-regulate the expressions of calreticulin and major histocompatibility complex I (MHC-I) on the tumor cell membrane surface, suggesting that α-particle internal irradiation may activate an endogenous antitumor immune response through the regulation of immune cells in the tumor microenvironment, which could synergically enhance the efficacy of immunotherapy. We conclude that [At]SAB-Oct is a potential new therapeutic option for SSTR2-positive SCLC.

In SSTR2-positive xenograft-bearing mice, the combination of nedisertib (a DNA-PK specific inhibitor) and LuTate produced a more robust control of tumour growth and increased survival compared to LuTate alone. DDR pathways are critical for sensing and repairing radiation-induced DNA damage, and our study shows that regulation of DDR pathways may be involved in both resistance and sensitivity to PRRT. Additionally, the use of a DNA-PK inhibitor in combination with LuTate PRRT significantly improves the efficacy of the treatment in pre-clinical models, providing further evidence for the clinical efficacy of this combination.

[68Ga]-DOTATATE PET can improve the specificity of imaging-based assessment of the extent of resection of WHO-2 meningiomas, thereby improving clinical outcomes. In this cohort of patients with completely resected WHO-2 meningiomas (as assessed by postoperative gadolinium-enhanced MRI and DOTATATE PET) who are conservatively managed, recurrences have been rare and amenable to radiosurgical salvage.

[68Ga]-DOTATATE PET can improve the specificity of imaging-based assessment of the extent of resection of WHO-2 meningiomas, thereby improving clinical outcomes. In this cohort of patients with completely resected WHO-2 meningiomas (as assessed by postoperative gadolinium-enhanced MRI and DOTATATE PET) who are conservatively managed, recurrences have been rare and amenable to radiosurgical salvage.

Targeting SSTR2 positive meningioma cells with an adaptor FITC CAR T-cell system is feasible. Syngeneic murine models and the use of adaptor molecules directed against murine SSTR2 will be required to explore secondary immune reactions and off-tumor effects prior to proceeding to early phase clinical trials.

In particular, SSTR2 expression is clinically valid because it is associated with metastatic disease at the time of diagnosis and can thus serve as a prognostic marker. Moreover, SSTR2 overexpression provides a molecular basis for tumour imaging and treatment with somatostatin analogues.

Our study is the first to shed light on the intricate relationship between SSTR2 and EGFR in NPC and provides new insights into the potential benefits of EGFR targeted therapy for patients with high SSTR2 expression. Additionally, SSTR2 has potential as a new biomarker for poor prognosis in NPC patients.

P2, N=100, Not yet recruiting, Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

OC patients displayed a significant inverse relationship between SSTR2 and TSHR expression that was not seen in OA patients. This may be a key relationship that can be utilized to prognosticate and treat OCs.

The anti-tumor effect was further enhanced when RYZ101 was combined with carboplatin and etoposide at clinically relevant doses. In summary, RYZ101 is a highly potent, alpha-emitting radiopharmaceutical agent, and preclinical data demonstrate the potential of RYZ101 for the treatment of patients with SSTR-positive cancers.

This result demonstrates consistent and strong expression of SSTR2 in PAs as compared to Warthin tumors, which may allow physicians to utilize radioligand-somatostatin analog PET CT/MR imaging to diagnose the PA. SSTR2 positivity, if shown to be clinically relevant, may allow peptide receptor radionuclide therapy in the future.

P1/2, N=52, Not yet recruiting, Viewpoint Molecular Targeting | Initiation date: Mar 2023 --> Jul 2023

Somatostatin receptor 2-negative nonfunctional pNET might represent a subtype of pNET with poor outcomes and evolve from a different genomic background.

In addition, a previous report showed high SSTR2 expression in ECL-cell NETs and gastrinomas, which could be because they are derived from neuroendocrine cells with high SSTR2 expression. This study may contribute to understanding the expression of SSTR2 in GI-NETs.

P2, N=20, Recruiting, Jules Bordet Institute | Trial completion date: Sep 2022 --> Sep 2023 | Trial primary completion date: Sep 2022 --> Sep 2023

SSTR2 expression was independently associated with SDHB/SDHx mutations and metastatic disease. We confirm a high disease control rate of somatostatin receptor-based therapies in metastatic PPGLs.

P=N/A, N=200, Recruiting, Weill Medical College of Cornell University | N=98 --> 200 | Trial completion date: Dec 2022 --> Dec 2038 | Trial primary completion date: Dec 2022 --> Dec 2038

EBV does not induce SSTR2 expression in non-Hodgkin lymphomas, however, there appears to be a relationship between EBV and SSTR2 in cHL. High grade GC-derived B-cell lymphomas (HGBL, DLBCL and FL grade 3) and PC neoplasms also show a high frequency of SSTR2 expression relative to non-GC B-cell lymphomas, suggesting that EBV+ cHL, high-grade GC-derived B-cell lymphomas and PC neoplasm may be targeted for imaging and/or therapy with SSTR2 agonists.

P1/2, N=52, Not yet recruiting, Viewpoint Molecular Targeting

The biodistribution and accumulation pattern in MPC tumor-bearing mice was also evaluated. The Lu and Ac complexes studied show how ligand structures can be optimized in general by extending the denticity and varying the donor set in order to allow for fast complex formation and medically relevant inertness.

In vivo biodistribution studies demonstrated high tumor uptake and rapid renal clearance for [203Pb]PSC-PEG2-TOC. The administration of 4 fractionated doses of [ 212Pb]PSC-PEG2-TOC produced 100% complete tumor responses at 100 days post therapy initiation and was well-tolerated compared to [177Lu]DOTATATE, which produced improved PFS (28.5 days), but no complete responses.CONCLUSIONS These data demonstrate that [203/212Pb]PSC-PEG2-TOC has the potential to produce a higher rate of objective tumor responses than beta-particle emitting therapeutics for NETs.

P=N/A, N=98, Recruiting, Weill Medical College of Cornell University | Trial completion date: Sep 2022 --> Dec 2022 | Trial primary completion date: Sep 2022 --> Dec 2022

P2, N=32, Recruiting, NYU Langone Health | Trial completion date: May 2023 --> May 2025 | Trial primary completion date: May 2022 --> May 2024

Results A total of 116 cases of meningiomas were included in this study,with the male-to-female ratio of 1.0∶2.6 and the age of 4-73 years.The main clinical symptom was headache.The imaging examination showed that 114 cases had single lesions and 2 cases had multiple lesions.The tumors were located in the cranium (108 cases) and spinal canal (8 cases).The maximum diameter of the tumors ranged from 0.3 cm to 10.0 cm,with a mean of (5.7±2.2) cm.In terms of microscopic grading and histological types,the 116 cases included 111 cases of WHO grade Ⅰ (including 53 cases of fibrous type,20 cases of meningothelial type,24 cases of transitional type,10 cases of psammomatous type,etc.),4 cases of WHO grade Ⅱ (3 cases of atypical type and 1 case of clear cell type),and 1 case of WHO grade Ⅲ (papillary type).The immunohistochemical staining showed H3K27me3 expression absent in 9 cases (9/116,7.8%),MUC4 positive in 64 cases (64/116,55.2%),SSTR2 positive in 101 cases (101/116,87.1%).Eighty cases had follow-up results,among which 71 cases had no recurrence,while 9 cases recurred. Conclusions Meningioma is the most common tumor in the central nervous system in the pathological file of Tibet.It mainly attacks the middle-aged female patients,occupying the parasagittal sinus,falx,and convex surface of the brain.Fibrous meningioma of WHO grade Ⅰ is common,while the meningiomas of WHO grades Ⅱ and Ⅲ are rare.The expression degree of MUC4 is higher in meningothelial and transitional meningiomas but lower in fibrous meningiomas.There may be no correlation between the absence of H3K27me3 expression and prognosis.

We experienced a case of severe ectopic ACTH producing the largest reported recurrent malignant left PCC with liver metastases that presented positive feedback loops in the ACTH/cortisol and catecholamine/cortisol axes. Clinicians should be aware of the paradoxical response of ACTH on metyrapone treatment and possible steroid-induced catecholamine crisis.

[Ga]Ga-DOTA-SSTR PET studies may revolutionize the routine neuro-oncology practice, especially in meningiomas, by improving diagnostic accuracy, delineation of radiotherapy targets, and patient eligibility for radionuclide therapies.