99mTc-p5+14 Imaging for Amyloidosis

Overseen By Emily B Martin, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Tennessee Graduate School of Medicine

Must not be taking: Heparin, Heparin analogs

Disqualifiers: Pregnancy, Dialysis, Psychosis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 days

35 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new imaging method to detect amyloid deposits in individuals with systemic amyloidosis, a condition where abnormal proteins accumulate in organs, particularly the heart. The study employs a special radiotracer, 99mTc-p5+14, to visualize these deposits during scans. Individuals with a confirmed diagnosis of systemic AL or ATTR amyloidosis with heart involvement, or healthy individuals without amyloidosis, may qualify for this trial. Participants will receive a tracer injection and undergo imaging to evaluate its effectiveness. As a Phase 1 trial, this research aims to understand how the treatment functions in people, offering participants the chance to be among the first to experience this innovative approach.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have received heparin or similar drugs within seven days before the study.

What prior data suggests that 99mTc-p5+14 is safe for detecting amyloid deposits?

Research has shown that 99mTc-p5+14 can detect amyloid deposits in the body, which is crucial for conditions like AL or ATTR amyloidosis that affect the heart. Studies have tested 99mTc-p5+14 on both healthy individuals and patients with amyloidosis. Both groups tolerated the radiotracer well, with no major side effects reported. This suggests it is safe for human use, although researchers continue to monitor safety closely.

Earlier animal studies found the radiotracer to be stable and specific, effectively targeting amyloid deposits without causing harm. This finding increases confidence in its safety for humans, although additional data remains valuable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about the treatment 99mTc-p5+14 for amyloidosis because it offers a novel approach to imaging the disease. Unlike traditional imaging methods, such as those using Pyrophosphate (PYP) scans, 99mTc-p5+14 aims to provide clearer and more precise images of amyloid deposits in the body. This new imaging agent could potentially allow for earlier and more accurate diagnosis, which is crucial for managing amyloidosis effectively. Additionally, its ability to provide detailed biodistribution data in both patients with amyloidosis and healthy subjects could enhance our understanding of how the disease progresses and how treatments can be more effectively tailored.

What evidence suggests that 99mTc-p5+14 is effective for detecting amyloid deposits in systemic amyloidosis?

Research has shown that 99mTc-p5+14 is a promising tool for detecting harmful protein buildups, known as amyloid deposits, in the heart and other tissues. These buildups are linked to conditions like AL and ATTR amyloidosis. In this trial, participants will receive 99mTc-p5+14 to assess its biodistribution and dosimetry. The radiotracer 99mTc-p5+14 remains stable in the body and specifically targets amyloid deposits, focusing on problem areas without affecting other tissues. In patients with amyloidosis, this tracer has appeared in specific spots, helping to identify where the amyloid is concentrated. Overall, these findings suggest that 99mTc-p5+14 could be very useful in diagnosing and understanding heart issues related to amyloid. ^{1 2 3 6 7}

Who Is on the Research Team?

Jonathan S Wall, PhD

Principal Investigator

University of Tennessee Graduate School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults over 18 with confirmed systemic AL or ATTR amyloidosis, particularly affecting the heart. Participants must be in good health, understand and consent to study procedures, and women of childbearing potential must test negative for pregnancy. Exclusions include severe allergies, certain heart conditions, liver issues, claustrophobia preventing imaging protocol completion, dialysis patients, pregnant or breastfeeding individuals.

Inclusion Criteria

I agree to use birth control if there's any chance of pregnancy with my partner.

I am a woman who can have children and have a recent negative pregnancy test.

I have been diagnosed with AL or ATTR amyloidosis.

Exclusion Criteria

I have taken heparin or similar drugs in the last week.

You are allergic to potassium iodide.

I do not have any health conditions that could interfere with the study or increase my risk.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single IV dose of 99mTc-p5+14 and undergo imaging to evaluate dosimetry and biodistribution

8 days

Multiple imaging sessions including planar and SPECT/CT

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 99mTc-p5+14

Trial Overview The study tests a synthetic peptide called 99mTc-p5+14 labeled with technetium-99m as a radiotracer to detect amyloid deposits in patients with cardiac involvement due to AL or ATTR-associated systemic amyloidosis. It aims to assess the effectiveness of this new diagnostic tool.

How Is the Trial Designed?

Group I: Estimation of dosimetry for 99mTc-p5+14 and Biodistribution Of 99mtc-p5+14 In Healthy Subjects Experimental Treatment 1 Intervention

For dosimetry, patients with a confirmed diagnosis of systemic AL amyloidosis, patients will be administered a single IV dose of up to 1 mg of 99mTc-p5+14 (\~20 mCi) by slow push (\~1 mL/5 sec.). Patients will then undergo serial planar scintigraphic imaging at \~30 minutes, \~1 hour, \~2 hours, \~4 hours, \~6 hours, and \~24 hours post-injection. At the 4-hour time point, the patient will also undergo a single SPECT/CT scan to provide additional data for estimating dosimetry. Before injection of the radiotracer and at each imaging session, \~2 -3 mL of blood will be acquired to determine the whole blood radioactivity. Healthy volunteers will undergo an echo examination, thereafter, they will be administered a single IV dose of 99mTc-p5+14 (20 mCi) and will undergo a single planar image acquisition followed by SPECT/CT imaging at \~1 hour and \~3 hours post-injection.

Group II: Biodistribution in patients with systemic AL or ATTR amlyoidosis Experimental Treatment 1 Intervention

Patients with a confirmed diagnosis of systemic AL or ATTR (with or without a positive PyP scan) will be administered a single IV dose of up to 1 mg of 99mTc-p5+14 (\~20 mCi) by slow push (\~1 mL/5 sec.). At \~1 hour and \~3 hours post-injection, patients will undergo abdominothoracic planar imaging followed by SPECT/CT imaging covering the same area. Vital signs (blood pressure, respiration rate, temperature, and pulse) will be acquired before injection of the 99mTc-p5+14, and at \~3 hours post injection. On Day 3, patient will undergo a trans thoracic echo examination. On Day 4, patients will undergo Technescan™ 99mTc-PYP (20 mCi) planar and SPECT/CT imaging at \~1 hour and \~3 hours post-injection. Vital signs (blood pressure, respiration rate, temperature, and pulse) will be acquired before injection of the 99mPYP, and at \~3 hours post injection.

Who Is Running the Clinical Trial?

University of Tennessee Graduate School of Medicine

Lead Sponsor

Trials

17

Recruited

1,400+

Attralus, Inc.

Industry Sponsor

Trials

8

Recruited

670+

Published Research Related to This Trial

The Tc-99m labeled peptide p5 + 14 was successfully developed as a radiotracer for SPECT imaging of systemic peripheral amyloidosis, showing a high radiochemical yield of 75% and over 90% purity, indicating its potential effectiveness for clinical use.

In mouse models, [(99m)Tc]p5 + 14 demonstrated specific uptake in amyloid-laden organs, with levels approximately five times higher than in healthy tissues, confirming its ability to accurately visualize amyloid deposits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tc-99m Radiolabeled Peptide p5 + 14 is an Effective Probe for SPECT Imaging of Systemic Amyloidosis. Kennel, SJ., Stuckey, A., McWilliams-Koeppen, HP., et al.[2019]

Over a 10-year period, the study found a low prevalence of adverse reactions to radiopharmaceuticals, with only 3.1 reports per 100,000 administrations in 2013 and 2.5 per 100,000 in 2015, indicating a generally safe profile for these substances.

The most common adverse reactions reported were rash, itching, and vomiting, with the highest number of reports associated with the radiopharmaceuticals tetrofosmin and oxidronate, suggesting that while reactions can occur, they are infrequent and typically mild.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Radiopharmaceutical Adverse Reaction Reports to the British Nuclear Medicine Society from 2007 to 2016. Kennedy-Dixon, TG., Gossell-Williams, M., Cooper, M., et al.[2018]

Adverse reactions to radiopharmaceuticals are rare, with an estimated incidence of 1 to 6 reactions per 100,000 injections, and most reactions are mild and transient, requiring little to no medical treatment.

The most common adverse effects are associated with diphosphonates and colloids, leading to symptoms like nausea, erythema, and hypotension, with serious reactions being rare but possible, particularly in patients on certain medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reactions and drug interactions with radiopharmaceuticals. Sampson, CB.[2018]

123I-labeled SAP scintigraphy demonstrated high diagnostic sensitivity for systemic AA and AL amyloidosis (90% each) and good specificity (93%), making it a reliable tool for identifying these types of amyloidosis in patients.

The technique revealed more extensive organ involvement than what was clinically detected, particularly showing frequent splenic amyloid deposits in AA and AL types, which were often missed in clinical evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic performance of 123I-labeled serum amyloid P component scintigraphy in patients with amyloidosis. Hazenberg, BP., van Rijswijk, MH., Piers, DA., et al.[2022]

A new synthetic peptide, p5+14, has been developed as a radiotracer for noninvasive imaging of amyloidosis, which could help in evaluating the whole-body amyloid load in patients.

The study supports moving forward to a phase 1 clinical trial using this radiotracer labeled with iodine-124 for positron emission tomography (PET) imaging in patients with systemic amyloidosis, potentially improving diagnosis and management of this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual-Energy SPECT and the Development of Peptide p5+14 for Imaging Amyloidosis. Wall, JS., Kennel, SJ., Martin, EB.[2020]

In a study of 14,794 injections of various radiopharmaceuticals over 18 months, only three side effects were reported, indicating a very low prevalence of adverse reactions, estimated at 0.02% for serious side effects.

The side effects included one case of necrosis, one case of vomiting, and one case of dizziness, all associated with Tc99m-pyrophosphate, with favorable outcomes for all cases, suggesting that radiopharmaceuticals are generally safe when administered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prospective survey on adverse effects of radiopharmaceuticals]. Bagheri, H., Galian, ME., Bastie, D., et al.[2015]

In a study of 94 children, metrizamide (Amipaque) provided examination quality in the lumbar-low thoracic region comparable to iophendylate, but it still required supine myelography in many cases.

Metrizamide was associated with higher side effects, such as nausea, vomiting, and fever, compared to previous reports in adults, although it offers advantages like better absorption and improved visualization of the conus in the prone position.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pediatric myelography with metrizamide. Fitz, CR., Harwood-Nash, DC., Barry, JF., et al.[2015]

Between 1977 and 1983, reports to the UK Adverse Reaction Reporting Scheme indicated a significant increase in adverse reactions related to radiopharmaceuticals, particularly due to the introduction of methylene diphosphonate for bone imaging, which accounted for nearly half of the recent reports.

The majority of reported reactions were idiosyncratic hypersensitive reactions, with an estimated incidence rate of 1 in 1,000 to 1 in 10,000 for in vivo nuclear medicine procedures, which is notably higher than previous estimates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reactions to radiopharmaceuticals. United Kingdom 1977-1983. Keeling, DH., Sampson, CB.[2016]

The peptide p5+14 can non-invasively detect all types of systemic amyloidosis by binding to amyloid deposits, which is crucial for early diagnosis and better patient outcomes.

In a Phase 1/2 clinical trial involving 8 patients with different types of amyloidosis, PET/CT imaging showed that the iodine-124-labeled p5+14 effectively localized amyloid deposits in affected organs, confirming its potential as a diagnostic tool.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Confirmation of Pan-Amyloid Reactivity of Radioiodinated Peptide 124I-p5+14 (AT-01) in Patients with Diverse Types of Systemic Amyloidosis Demonstrated by PET/CT Imaging. Martin, EB., Stuckey, A., Powell, D., et al.[2023]

The first-in-human study of the iodine-124 labeled peptide 124I-p5+14 demonstrated that it is well tolerated and rapidly accumulates in organs commonly affected by amyloidosis, such as the heart, kidneys, and liver, indicating its potential for effective imaging of amyloid deposits.

Dosimetry estimates for 124I-p5+14 were found to be acceptable for whole-body PET/CT imaging, with a low effective radiation dose of 0.23 mSv/MBq, suggesting that this imaging technique could be a safe and non-invasive method for diagnosing systemic AL amyloidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First in Human Evaluation and Dosimetry Calculations for Peptide 124I-p5+14-a Novel Radiotracer for the Detection of Systemic Amyloidosis Using PET/CT Imaging. Wall, JS., Martin, EB., Endsley, A., et al.[2022]

A study involving 233 patients with suspected transthyretin cardiac amyloidosis demonstrated that a 1-hour imaging protocol using technetium-99 m pyrophosphate is as effective as the traditional 3-hour protocol for diagnosing the condition.

The 1-hour planar imaging showed high sensitivity (98%) and specificity (96%), indicating it can reliably identify patients with diffuse myocardial uptake, making it a more efficient option for diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficient 1-Hour Technetium-99 m Pyrophosphate Imaging Protocol for the Diagnosis of Transthyretin Cardiac Amyloidosis. Masri, A., Bukhari, S., Ahmad, S., et al.[2021]

Scintigraphy using 99mTc-labeled methylene-diphosphonate (99mTc-MDP) and pyrophosphate (99mTc-PYP) is an effective noninvasive screening method for assessing organ involvement in various types of amyloidosis, including systemic AA and AL amyloidosis.

While 99mTc-MDP and 99mTc-PYP scintigraphy are useful for detecting amyloidosis, echocardiography is more sensitive for identifying cardiac involvement, highlighting the need for complementary diagnostic approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Soft-tissue uptake of 99mTc-diphosphonate and 99mTc-pyrophosphate in amyloidosis. Janssen, S., Piers, DA., van Rijswijk, MH., et al.[2019]

Citations

1. jnm.snmjournals.org jnm.snmjournals.org/content/65/supplement_2/241277

Preliminary Evaluation of 99mTc-Labeled Peptide p5+14 ... 99m Tc-p5+14 is a promising new reagent for the facile detection of amyloid cardiomyopathy of any type using gamma scintigraphic imaging.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4874933/

Tc-99m Radiolabeled Peptide p5+14 is an Effective Probe ... The [99mTc]p5+14 retains amyloid specificity and exhibits in vivo stability as evidenced by quality assurance assays, serial SPECT/CT scanning, and ...

3. attralus.com attralus.com/press-releases/attralus-presents-new-data-on-its-pan-amyloid-diagnostic-imaging-candidates-at-asnc-2025

Attralus Presents New Data on Its Pan-Amyloid Diagnostic ... In ATTR patients, 99mTc-p5+14 was observed in focal lesions and pleura of the lungs as well as joints. In patients with cardiac AL amyloidosis, ...

4. oneamyloidosisvoice.com oneamyloidosisvoice.com/rarehub/phase-1-study-99mtc-p514-healthy-volunteers-and-patients-al-or-attr-systemic-amyloidosis

A Phase 1 Study of 99mTc-p5+14 in Healthy Volunteers and ... When radiolabeled with 99mTc, p5+14 may enable visualization of amyloid laden tissues and organs by SPECT/CT imaging or PGS. Thus, this study has been designed ...

5. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/486315

A Phase 1 Study of 99mTc-p5+14 in Healthy Volunteers and ... For dosimetry, patients with a confirmed diagnosis of systemic AL amyloidosis, patients will be administered a single IV dose of up to 1 mg of 99mTc-p5+14 (~20 ...

6. jnm.snmjournals.org jnm.snmjournals.org/content/65/supplement_2/24113

A Novel Radiotracer for SPECT/CT Imaging of Cardio ... Extracellular cardiac deposits of amyloid are a common manifestation in patients with AL or ATTR amyloidosis and portend a poor prognosis.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10997057/

Preclinical evaluation of Tc-99m p5+14 peptide for SPECT ... Data from this early phase study support use of the peptide reagent as a method for detecting amyloid in patients with AL, ATTR, and other rare ...