Project title: COPPER PET with 61Cu-NODAGA-LM3 for the detection of Neuroendocrine Tumors

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Description

This study evaluates Copper-61 (61Cu)-tagged NODAGA-LM3, a new drug under development, for the detection of NET. 61Cu-NODAGA-LM3 is a unique positron emission tomography (PET) imaging agent with properties that may outperform the standard-of-care PET agents. 

What critical NET problem/question will researchers try to answer?

Dr. Fani is exploring whether NET patients can have better access to the state-of-the-art PET scan by making this procedure less expensive and more widely available while improving the detection of tumors by introducing a better drug.

Why is this important?
The new drug, 61Cu-NODAGA-LM3, is expected to combine performance (including patient safety), precision and broad low-cost availability. It can potentially increase the sensitivity and diagnostic accuracy of PET imaging of NETs, compared with currently used drugs for the same purpose (e.g., 68Ga-DOTATATE, 68Ga-DOTATOC or 64Cu-DOTATATE).

What will the researchers do?

Dr. Fani and the research team will first establish the production of 61Cu at two sites in Europe (Switzerland and Germany) using the proprietary technology of Nuclidium AG (collaborator in the project). They will then establish the production of 61Cu-NODAGA-LM3 for human use and launch a clinical phase 0/I study in Switzerland to assess the safety, biodistribution, pharmacokinetics and dosimetry of 61Cu-NODAGA-LM3 in NET patients. The study is also expected to incorporate a head-to-head comparison of 61Cu-NODAGA-LM3 with 68Ga-DOTATOC PET/CT in the same patients. 

How might this improve treatment of NETs?

Patients who have a NET may benefit from improved image quality and also better access to this state-of-the-art imaging procedure, which is required for staging, restaging, therapy planning and monitoring. Furthermore, another radioisotope of copper, 67Cu, can be used for therapy. 61Cu-NODAGA-LM3 and 67Cu-NODAGA-LM3 are structurally identical and have identical distribution in the body. 61Cu-NODAGA-LM3 can therefore be used for precise tumor detection and individual NET patient selection for those who benefit most from therapy with 67Cu-NODAGA-LM3 (the “see what you treat, and treat what you see” concept). This is an ideal theragnostic approach for more personalized and efficacious care for patients who have NETs.

What is the next step?

The study by Dr Fani and the research team will pave the way for further clinical evaluation of 61Cu-NODAGA-LM3. A phase II study in Switzerland, Germany and the United States is already planned upon completion of this phase 0/1 study. Afterward, Nuclidium AG (industrial collaborator in this project) has an interest in commercializing 61Cu-NODAGA-LM3 in the United States and other countries.

Outcomes:

We aim to develop 61Cu-NODAGA-LM3, a best-in-class, widely available, and more affordable PET imaging drug for neuroendocrine tumor (NET) patients. This Copper-61-tagged compound addresses the limitations of current somatostatin receptor imaging agents.

The project’s first goal is to produce high-quality Copper-61 (Cu-61) and enable its delivery to hospitals at varying distances from production sites. Cu-61 production is planned at two locations: Zurich, Switzerland, and Munich, Germany, with delivery to the University Hospital in Basel (~90 km from Zurich and ~400 km from Munich).

Three milestones were achieved in the first year:
1. Optimizing Cu-61 purification: We used enriched materials and implemented necessary installations for the process. High-quality, sterile Cu-61 production was achieved via automated purification, with quality controls and specifications carefully defined. Swiss authorities reviewed the process to ensure regulatory compliance.
2. Setting up production in Munich: Zurich’s process was successfully transferred to Munich, and reproducibility tests are ongoing. Specifications and production consistency were confirmed.
3. GMP production and delivery: Cu-61 was produced under GMP conditions, meeting defined specifications for validating the 61Cu-NODAGA-LM3 manufacturing process. Logistics were established, and three successful production runs validated the process.

The project’s second goal was to conduct a clinical phase 0/I study of 61Cu-NODAGA-LM3 in 8 patients with GEP and BP NET. Four milestones were set and achieved in the first year:
1. Preparation of clinical study documentation: Additional documents for the quality dossier and investigator’s brochure of 68Ga-DOTATOC, the standard-of-care comparator drug, were submitted as requested by Swiss authorities.
2. GMP production setup for 61Cu-NODAGA-LM3: The drug’s production for human use was finalized following strict Good Manufacturing Practice (GMP) standards. All devices and materials were qualified, and the process was validated for robustness, purification, and yield. Quality control methods were validated, and clinical study batches identical to those for human use were completed by October 2023.
3. Regulatory and ethical approvals: The ethics committee approved the study on March 13, 2024, and conditional approval from Swissmedic and the Federal Office of Public Health was granted on September 11, 2024. A revised Investigational Medicinal Product Dossier (IMPD) for 61Cu was resubmitted and conditions were fulfilled by January 2025.
4. Validation of GMP manufacturing: The GMP manufacturing process for 61Cu-NODAGA-LM3 was successfully validated, and the data were submitted to Swiss authorities as part of the clinical trial documentation.

All predefined milestones were successfully achieved, including completion of enrolment for the first 8 patients within just 2 months. Thanks to the promising early results and the instrumental seeding support from NETRF, the study could be transitioned into a larger, randomized, controlled, reader-blind Phase I/II PET/CT trial (NCT06455358). This ongoing study includes 22 patients with SSTR2-positive, well-differentiated gastroenteropancreatic or bronchopulmonary neuroendocrine tumors. All patients are expected to be enrolled at the University Hospital Basel by the end of July 2025.

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