Biodistribution and Safety of the PET Probes [18F]FPRGD2 and [18F]FPPRGD2

The purpose of the study was to conduct a pilot test of new tracers ([18F]FPRGD2 and [18F]FPPRGD2) to define normal tracer biodistribution (where the tracer goes), stability (how much metabolises), pharmacokinetics (how much stays in which organs and for how long), and radiation dosimetry (organ radiation dose). Healthy volunteers provided the normal biodistribution data.

The same radiopharmaceutical was also tested in breast cancer, glioblastoma multiform (brain cancer), and lung cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Glioblastoma; Non-Small-Cell Lung Cancer; Other Cancers
• Intervention / Treatment: Drug: F18-FPPRGD2

Detailed Description

The tracer [18F]FPRGD2 was not evaluated in this study. The protocol title was never amended to reflect this.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Study Population

Stanford Clinic patients

Description

Inclusion Criteria:

Healthy volunteers:

1. Must be 18 years of age or older.
2. Must have no known medical problems and have had a full medical exam within 6 months of the study.
3. Must understand and voluntarily have signed an Informed Consent after its contents have been fully explained.
4. Women of child bearing potential (as defined as women who are not post menopausal for 12 months or who have had no previous surgical sterilization).
5. Men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 30 days after the last dose.

Cancer subjects:

1. Greater than 18 years-old at the time of radiotracer administration
2. Provides written informed consent
3. Diagnosed with advanced non-small cell lung cancer (NSCLC), breast cancer, pancreatic cancer and glioblastoma multiforme (GBM); patients will undergo bevacizumab or Cyberknife therapy
4. Able to remain still for duration of each imaging procedure (about one hour)

Exclusion Criteria

1. Less than 18 years-old at the time of radiotracer administration
2. Pregnant or nursing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Healty Volunteers; Normal volunteers to receive 5 to 14 mCi F18-FPPRGD2 by intravenous (IV) injection.	Drug: F18-FPPRGD2; Radiopharmaceutical administered for imaging, up to 14 mCi intravenous (IV).
Experimental: Breast Cancer; Breast cancer patients to receive 4 to 11 mCi F18-FPPRGD2 by IV injection.	Drug: F18-FPPRGD2; Radiopharmaceutical administered for imaging, up to 14 mCi intravenous (IV).
Experimental: Glioblastoma Multiform (brain); Glioblastoma multiform patients to receive 5 to14 mCi F18-FPPRGD2 by IV injection.	Drug: F18-FPPRGD2; Radiopharmaceutical administered for imaging, up to 14 mCi intravenous (IV).
Experimental: Lung Cancer; Lung cancer patients to receive X to XX mCi F18-FPPRGD2 by IV injection.	Drug: F18-FPPRGD2; Radiopharmaceutical administered for imaging, up to 14 mCi intravenous (IV).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tracer Dosimetry by Organ	Normal radiopharmaceutical biodistribution was analyzed visually to obtain dosimetry data in healthy volunteers. Organs with the highest radiation absorbed dose (dosimetry) are provided below. Dosimetry was calculated by drawing regions-of-interest around organs with visually appreciable radiopharmaceutical uptake greater than background and using organ-level internal dose assessment software from Vanderbuilt University (2003). Results are reported in mSv/MBq (milli-Sieverts per mega-Bequerel) which is a measurement of the mean absorbed radiation dose within an organ.	5 hours
F18-FPPRGD2 Time-activity at Specified Timepoints	Radiopharmaceutical pharmacokinetics describe the change in radiopharmaceutical distribution in the body (from the blood to organs, tissues, cells) over time. Radiopharmaceutical pharmacokinetics are used to determine optimal imaging time, ie, when target activity (organ or cell of interest) is greater than background activity (blood). Optimal imaging time must also be balanced with tracer bio-metabolism and radioactive decay. F18-FPPRGD2 pharmacokinetics was measured in healthy volunteers to estimate optimal imaging time. Scans were used to visually identify regions of interest (organs of F18-FPPRGD2 accumulation), and detected radiation was plotted as a measurement over time.	30, 60, and 90 minutes post-injection
Sensitivity of F18-FPPRGD2 PET/CT in Breast Cancer	Sensitivity is the ability of a test to correctly identify patients with the disease being investigated. In this instance, how well F18-FPPRGD2 PET/CT detects true-positive patients. Sensitivity is defined as [TP/ (TP+FN)], where TP= true positive, and FN = false negative. The outcome is reported as a percentage without dispersion. A higher percentage indicates a greater probability that a lesion identified based on scan results is cancerous, and a lower percentage indicates reduced confidence in that result.	3 hours
Specificity of F18 FPPRGD2 PET/CT in Breast Cancer	Specificity is the ability of a test to correctly identify patients who do not have the disease being investigated. In this instance, how well F18 FPPRGD2 PET/CT detects true-negative patients. Specificity is: [TN/ (TN+FP)], where TN= true negative, and FP = false positive.	an estimated average of 3 hours
Glioblastoma Primary Tumor Response Assessed by PET Scan	Primary tumor response was assessed after 6 weeks of treatment as the change in tumor metabolism based on the maximum standardized uptake value (SUVmax) as determined by positron emission tomography (PET) scans. Decreased SUVmax correlates to a reduction of tumor metabolism, and is considered an indicator of primary tumor response. Reduction of SUVmax was determined as the change from baseline in uptake of F-18FPPRGD2. The outcome is reported as the baseline and week 6 values, with standard deviation.	Baseline and Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glioblastoma Primary Tumor Response Assessed by CT Scan	Primary tumor response was assessed after 6 weeks of treatment as the change in tumor metabolism based on the maximum standardized uptake value (SUVmax) as determined by computed tomography (CT) scans. Decreased SUVmax correlates to a reduction of tumor metabolism, and is considered an indicator of primary tumor response. Reduction of SUVmax was determined as the change from baseline in uptake of F-18FPPRGD2. The outcome is reported as the mean difference from baseline to week 6, with standard deviation.	Baseline and Week 6

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Sanjiv Gambhir, MD, PhD, Stanford University

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: May 31, 2011
• First Submitted That Met QC Criteria: June 24, 2011
• First Posted (Estimated): June 28, 2011

Study Record Updates

• Last Update Posted (Actual): January 12, 2024
• Last Update Submitted That Met QC Criteria: April 14, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Healthy volunteers
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: IRB-16118; VAR0047 (Other Identifier: OnCore Number); SU-09022010-6791 (Other Identifier: Stanford University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No