Feasibility of [11C]Acetate-PET in LAM and TSC

NCT ID: NCT05467397

Last Updated: 2026-01-21

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-30
• Study Completion Date: 2026-06-30

Brief Summary

This study aims to assess [11C]acetate positron emission tomography (PET)/computed tomography (CT) as a biomarker for renal angiomyolipomas and pulmonary lymphangioleiomyomatosis (LAM) and an early biomarker of response to rapamycin in LAM patients.

[11C]Acetate is a radioactive form of acetate, a nutrient commonly processed in our body's cells to generate fat and energy. Preclinical studies support the hypothesis that TSC tumors enhance lipid synthesis compared to normal tissues, suggesting that quantification of [11C]acetate in these tumors by PET/CT may provide a metabolic biomarker of disease.

Participants in the study will undergo 1 or 2 PET/CT scans over 3 to 6 months at the Massachusetts General Hospital (Boston, MA). [11C]acetate is administered through an intravenous catheter. This small amount of radioactivity is short-lived and eliminated from the body within a few hours.

Detailed Description

Lymphangioleiomyomatosis (LAM) is a rare, multisystem disease of women, consisting of a diffuse proliferation of smooth muscle actin-positive cells (LAM cells), which harbor inactivating mutations in either the TSC1 or TSC2 tumor suppressor gene. These inactivating mutations result in constitutive activation of mammalian/mechanistic TOR (target of rapamycin) complex 1 (mTORC1), which integrates growth factor and nutrient signaling to stimulate cell growth and metabolism. Pulmonary LAM is characterized by associated progressive cystic destruction of the lung parenchyma, recurrent pneumothorax, and chylous pleural effusions. Extrapulmonary proliferative lesions of LAM include renal angiomyolipomas and lymphangiomyomas. LAM can occur as a sporadic disorder where LAM cells harbor somatic inactivating mutations of the TSC1 or TSC2 gene, or in women with Tuberous Sclerosis Complex (TSC).

Rapamycin is an FKBP12-dependent allosteric inhibitor of mTORC1 approved by the FDA for the treatment of LAM and TSC-associated renal angiomyolipomas. Clinical trials of TSC and LAM have shown that 12 month-treatment with rapamycin induces response of renal angiomyolipomas and stabilization of pulmonary function. However, lung function decline and tumor growth resume when treatment is interrupted.

Sensitive and specific biomarkers of response to therapy and/or disease progression, including biomarkers of tumor metabolic activity, would facilitate clinical trials of novel therapeutic agents for LAM and enable optimization of current rapamycin-based regimens.

Our preclinical studies showed that lipogenic pathways can be detected in preclinical animal models of TSC and LAM using PET-based metabolic imaging.

The proposed study aims to quantitatively and non-invasively assess metabolic activity and response to rapamycin in LAM patients using [11C]acetate positron emission tomography (PET) imaging.

Conditions

Lymphangioleiomyomatosis; Tuberous Sclerosis Complex

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Patients will undergo [11C]acetate PET/CT

Patients will undergo a single \[11c\]acetate PET scan OR Patients will undergo an \[11c\]acetate PET scan, initiate treatment with rapamycin or rapalogs and receive a second \[11c\]acetate PET scan 3 or 4 months after starting the treatment.

Group Type: EXPERIMENTAL

[11C]acetate

Intervention Type: DRUG

Positron Emission Tomography (PET)

Interventions

[11C]acetate

Positron Emission Tomography (PET)

Intervention Type: DRUG

Other Intervention Names

diagnostic test

Eligibility Criteria

Inclusion Criteria

• diagnosis of LAM (or TSC-LAM)
• age 18 or over
• at least one renal angiomyolipoma (at least 1 cm in each diameter) confirmed by CT or MRI
• no prior treatment with rapamycin/rapalogs OR candidate for initiating treatment with rapamycin/rapalogs OR under treatment with rapamycin/rapalogs for minimum 3 months and maximum of 1 year

Exclusion Criteria

• under treatment with rapamycin or rapalogs for < 3 months or > 1 year
• participated in research studies involving radiation exposure (> 50 mSv/year) in the past 12 months

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Carmen Priolo, M.D., Ph.D.

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Carmen P Priolo, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

2019p003557

Identifier Type: -

Identifier Source: org_study_id