Alpha-radiation Imaging for Neuroendocrine Tumors

Overseen By Yusuf Menda, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Yusuf Menda

Must not be taking: Investigational drugs, others

Disqualifiers: Pregnancy, Breastfeeding, Weight limit, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires a 24-hour discontinuation of somatostatin analogue therapy, unless your doctor thinks it's unsafe for you. If you're on long-acting somatostatin analogue treatment, it must be stopped at least 20 days before the first day of the study.

What data supports the effectiveness of the treatment [203Pb]VMT-α-NET for neuroendocrine tumors?

Research on similar treatments, like peptide receptor radionuclide therapy (PRRT) using alpha-emitting radionuclides, shows promising results for neuroendocrine tumors. These treatments have been effective in controlling disease progression and improving survival rates, with high tumor uptake and low toxicity to other organs. ^{1 2 3 4 5}

Is alpha-radiation imaging for neuroendocrine tumors safe for humans?

Research on similar treatments, like [225Ac]Ac-DOTATATE, shows partial responses in patients with neuroendocrine tumors without significant blood, kidney, or liver toxicity. However, more studies are needed to confirm the safety of [203Pb]VMT-α-NET specifically. ^{3 4 6 7 8}

How does the alpha-radiation treatment for neuroendocrine tumors differ from other treatments?

This treatment uses alpha particles, which have very high energy and a short path length, potentially making it more effective than traditional beta particle therapies. It targets neuroendocrine tumors more precisely, possibly leading to better outcomes with fewer side effects. ^{4 5 9 10 11}

What is the purpose of this trial?

This is a first in man study to determine if \[203Pb\]VMT-α-NET identifies neuroendocrine tumors with SPECT/CT. This is the first step to testing \[212Pb\]-based alpha radiation therapy in neuroendocrine therapy.

Research Team

Yusuf Menda, M.D.

Principal Investigator

University of Iowa

Eligibility Criteria

Adults over 18 with well-differentiated neuroendocrine tumors, confirmed by pathology, that are positive for somatostatin receptors and measurable on imaging. Participants must be able to consent, follow study procedures, have a good performance status, and not have severe illnesses or conditions affecting study compliance.

Inclusion Criteria

I can take care of myself and perform daily activities.

I have a tumor positive for somatostatin receptors, confirmed by a PET/CT scan within the last year.

My tumor is a Grade 1 or 2 neuroendocrine tumor, originating from the midgut or foregut.

Exclusion Criteria

Individuals who are pregnant or breast feeding. A pregnancy test will be administered to individuals of child-bearing potential (per institutional policies) at screening. Individuals must agree to pregnancy tests prior to each administration of a radionuclidic agent for this study.

Individuals of reproductive potential who decline to use effective contraception through the study (22 days equaling 10 half-lives).

I haven't taken any experimental drugs in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Imaging and Dosimetry

Participants receive a microdose of [203Pb]VMT-α-NET followed by serialized imaging and dosimetry measurements over 4 days

4 days

Daily imaging visits

Follow-up

Participants are monitored for safety and effectiveness after imaging

1 week

Treatment Details

Interventions

• [203Pb]VMT-α-NET

Trial Overview [203Pb]VMT-α-NET is being tested to see if it can identify neuroendocrine tumors using SPECT/CT imaging. This trial is the preliminary step before testing alpha radiation therapy for these types of tumors.

Participant Groups

Group I: [203Pb]VMT-α-NET SPECT/CT Experimental Treatment 2 Interventions

injection of \[203Pb\]VMT-α-NET with serialized imaging and dosimetry measurements

Who Is Running the Clinical Trial?

Yusuf Menda

Lead Sponsor

Trials

3

Recruited

70+

Viewpoint Molecular Targeting

Industry Sponsor

Trials

4

Recruited

570+

Holden Comprehensive Cancer Center

Collaborator

Trials

27

Recruited

710+

Perspective Therapeutics

Industry Sponsor

Trials

6

Recruited

710+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Targeted alpha therapy (TAT) using lead-212 (212Pb) shows promise for treating neuroendocrine tumors (NETs), with the study identifying [212Pb]Pb-eSOMA-01 as a leading candidate based on its high tumor uptake and low kidney absorption in tests with tumor-bearing mice.

The ligands developed for this therapy demonstrated high radiochemical yields and stability, with [212Pb]Pb-eSOMA-01 achieving the highest absorbed dose in tumors (35.49 Gy/MBq) while minimizing exposure to healthy tissues, indicating a potential for safer and more effective treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[212Pb]Pb-eSOMA-01: A Promising Radioligand for Targeted Alpha Therapy of Neuroendocrine Tumors. Chapeau, D., Koustoulidou, S., Handula, M., et al.[2023]

In a study of 11 patients with grade 1/2 metastatic neuroendocrine tumors treated with [225Ac]Ac-DOTATATE, the therapy demonstrated a high disease control rate of 89%, with 44.4% of patients showing a partial response and 44.4% having stable disease.

The treatment was found to be stable and safe, with only mild toxicities reported (grade 2 renal and hematotoxicity), and a median progression-free survival of 12 months, indicating its potential effectiveness for patients who were refractory to previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial Findings on the Use of [225Ac]Ac-DOTATATE Therapy as a Theranostic Application in Patients with Neuroendocrine Tumors. Demirci, E., Alan Selçuk, N., Beydağı, G., et al.[2023]

Neuroendocrine neoplasms (NEN), particularly well-differentiated types, can be effectively diagnosed and treated using peptide receptor radionuclide therapy (PRRT) with somatostatin receptor analogues, which have been shown to be a safe and effective treatment option following FDA and EMA approval of 177Lu-DOTATATE.

Current research is focused on enhancing the efficacy of PRRT and minimizing its toxicity through personalized treatment approaches, improved patient selection, and the development of new radiopharmaceuticals, indicating a promising future for NEN management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular imaging Theranostics of Neuroendocrine Tumors. Fortunati, E., Bonazzi, N., Zanoni, L., et al.[2023]

Targeted alpha-particle therapy (TAT) using radiopharmaceuticals like 225Ac-DOTATATE and 213Bi-DOTATOC shows promise in treating metastatic gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), with evidence of partial responses observed in the reviewed studies.

These therapies appear to have a favorable safety profile, as they did not show significant hematological, renal, or hepatotoxicity, suggesting they could be viable options after the failure of 177Lu-DOTATATE therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted alpha-particle therapy in neuroendocrine neoplasms: A systematic review. Koh, TT., Bezak, E., Chan, D., et al.[2022]

Peptide receptor radionuclide therapy (PRRT) is a promising treatment for neuroendocrine tumors (NETs), particularly in metastatic cases, contributing to improved progression-free and overall survival.

In a case study, a patient with over 50 abdominal lesions experienced almost complete disappearance of these lesions after a single dose of 225Ac-DOTATATE, an alpha particle-emitting radionuclide, highlighting its potential high efficacy compared to traditional beta-emitting radionuclides.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Almost Complete Response with a Single Administration 225Ac-DOTATATE in a Patient with a Metastatic Neuroendocrine Tumor of Unknown Primary. Alan Selçuk, N., Demirci, E., Ocak, M., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Neuroendocrine Tumor Therapy: 177Lu-DOTATATE. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Somatostatin Receptor 2-Targeting Compounds. [2018]

3. Poland pubmed.ncbi.nlm.nih.gov

Different technical possibilities of post-therapeutic tandem 90Y/ /177Lu-DOTATATE imaging. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

[212Pb]Pb-eSOMA-01: A Promising Radioligand for Targeted Alpha Therapy of Neuroendocrine Tumors. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Targeted Alpha Particle Therapy for Neuroendocrine Tumours: The Next Generation of Peptide Receptor Radionuclide Therapy. [2019]

6. Turkey pubmed.ncbi.nlm.nih.gov

Initial Findings on the Use of [225Ac]Ac-DOTATATE Therapy as a Theranostic Application in Patients with Neuroendocrine Tumors. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Molecular imaging Theranostics of Neuroendocrine Tumors. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

Targeted alpha-particle therapy in neuroendocrine neoplasms: A systematic review. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Contemporary nuclear medicine imaging of neuroendocrine tumours. [2016]

10. Italy pubmed.ncbi.nlm.nih.gov

Imaging neuroendocrine tumours with radionuclide techniques. [2016]

11. Turkey pubmed.ncbi.nlm.nih.gov

Almost Complete Response with a Single Administration 225Ac-DOTATATE in a Patient with a Metastatic Neuroendocrine Tumor of Unknown Primary. [2022]