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| Name | Class |
|---|---|
| Massachusetts General Hospital | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients will undergo [11C]acetate PET/CT | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [11C]acetate | Drug | Positron Emission Tomography (PET) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Quantitative Analysis of [11C]Acetate Uptake in LAM Lesions | Standardized uptake value (SUV) will be used to quantify uptake of [11C]acetate in kidney angiomyolipoma | Single assessment (day of imaging) |
| Measure | Description | Time Frame |
|---|---|---|
| Quantitative Analysis of [11C]Acetate Uptake in LAM Lesions Following Treatment With mTORC1 Inhibitor | Standardized uptake value (SUV) will be used to quantify uptake of [11C]acetate in kidney angiomyolipoma following treatment with mTORC1 inhibitor | Single assessment conducted while participants were on treatment with mTORC1 inhibitor (day of imaging) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Carmen P Priolo, MD PhD | Brigham and Women's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
One patient became ineligible after undergoing a renal procedure.
Seven women with Lymphangioleiomyomatosis (LAM) and at least one renal angiomyolipoma greater than 1 cm diameter were recruited to participate in the imaging study.
Patients were recruited between August 2021 and May 2024 and signed a consent form either in person or electronically.
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| ID | Title | Description |
|---|---|---|
| FG000 | Undergoing [11C]Acetate PET/CT Imaging | Patients underwent a single [11C]acetate positron emission tomography (PET)/computed tomography (CT) scan |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
One patient became ineligible after undergoing a renal procedure.
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| ID | Title | Description |
|---|---|---|
| BG000 | Undergoing [11C]Acetate PET/CT Imaging | Patients underwent a single [11C]acetate positron emission tomography (PET)/computed tomography (CT) scan |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | 18 years old or older |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Quantitative Analysis of [11C]Acetate Uptake in LAM Lesions | Standardized uptake value (SUV) will be used to quantify uptake of [11C]acetate in kidney angiomyolipoma | These participants had not received treatment with mTORC1 inhibitors at the time of imaging | Posted | Mean | Standard Deviation | Standardized Uptake Value (SUV) | Single assessment (day of imaging) |
|
|
From imaging up to 10 days
Risk of arterial catheter line (local swelling, redness, pain, infection)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Undergoing [11C]Acetate PET/CT Imaging | Patients underwent a single [11C]acetate positron emission tomography (PET)/computed tomography (CT) scan |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Carmen Priolo, MD PhD | Brigham and Women's Hospital, Boston, MA | 857-307-0783 | cpriolo@bwh.harvard.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 29, 2024 | Dec 2, 2025 | Prot_SAP_002.pdf |
| ICF | No | No | Yes | Informed Consent Form | May 29, 2024 | Dec 2, 2025 | ICF_003.pdf |
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| ID | Term |
|---|---|
| D018192 | Lymphangioleiomyomatosis |
| D014402 | Tuberous Sclerosis |
| ID | Term |
|---|---|
| D008203 | Lymphangiomyoma |
| D018190 | Neoplasm, Lymphatic Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C438206 | carbon-11 acetate |
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| Participants |
|
| Sex: Female, Male | Only women are affected by Lymphangioleiomyomatosis (LAM) | Count of Participants | Participants |
|
| Race (NIH/OMB) | No race was excluded | Count of Participants | Participants |
|
|
|
| Secondary | Quantitative Analysis of [11C]Acetate Uptake in LAM Lesions Following Treatment With mTORC1 Inhibitor | Standardized uptake value (SUV) will be used to quantify uptake of [11C]acetate in kidney angiomyolipoma following treatment with mTORC1 inhibitor | These participants were on treatment with mTORC1 inhibitor at the time of imaging | Posted | Mean | Standard Deviation | Standardized Uptake Value (SUV) | Single assessment conducted while participants were on treatment with mTORC1 inhibitor (day of imaging) |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 0 |
| 6 |
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| D054973 |
| Perivascular Epithelioid Cell Neoplasms |
| D018204 | Neoplasms, Connective and Soft Tissue |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D006222 | Hamartoma |
| D009378 | Neoplasms, Multiple Primary |
| D009386 | Neoplastic Syndromes, Hereditary |
| D065703 | Malformations of Cortical Development, Group I |
| D054220 | Malformations of Cortical Development |
| D009421 | Nervous System Malformations |
| D009422 | Nervous System Diseases |
| D020752 | Neurocutaneous Syndromes |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D030342 | Genetic Diseases, Inborn |