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

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.

Time frame: 30, 60, and 90 minutes post-injection

Population: Per protocol, data were collected for this outcome from the Healthy Volunteers group only. 4/5 volunteers were able to complete all of the scans. 1/5 participant could only complete one of the four scans and was not included in pharmacokinetic calculations.

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.

Time frame: Baseline and Week 6

Population: Per protocol, data were collected for this outcome from the Glioblastoma Multiforme group only. Participants in the Glioblastoma Multiforme group who completed the imaging schedule were included in the analysis.

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.

Time frame: 3 hours

Population: Per protocol, data were collected for this outcome from the Breast Cancer Patients group only. In a per-lesion analysis, a total of 30 lesions were evaluated at PET/CT scanning with F18-FPPRGD2.

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.

Time frame: an estimated average of 3 hours

Population: Per protocol, data were collected for this outcome from the Breast Cancer Patients group only. Other cohorts are not included, and the outcome was only assessed in the breast cancer cohort.

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.

Time frame: 5 hours

Population: Per protocol, data were collected for this outcome from the Healthy Volunteers group only, and only those that completed all scans are included.

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.

Time frame: Baseline and Week 6

Population: Per protocol, data were collected for this outcome from the Glioblastoma Multiforme group only. Participants in the Glioblastoma Multiforme group who completed the imaging schedule were included in the analysis.