This study is designed to assess the safety, biodistribution and dosimetry of the novel
atherosclerotic imaging PET radiotracer, Cu-25%-CANF-Comb.
This study is a single center, open-label baseline controlled imaging study designed to
demonstrate safety, biodistribution and dosimetry of the radiopharmaceutical
Cu-25%CANF-Comb (Cu = copper; CANF = C-type Atrial Natriuretic Factor) in healthy, adult
volunteers. By definition a "healthy" volunteer is an individual who, by physical exam and
baseline electrocardiogram, has no evidence of cardiovascular disease and, by history, is
not under the care of a physician for any active medical conditions.
Each volunteer will receive a single intravenous bolus injection of 4-8 mCi of the
investigational radiotracer Cu-25%CANF-Comb followed by whole body static PET-CT imaging
at 3 of 4 dedicated imaging time points, (1-4 hours, 5-10 hours, and 22-26 hours or 46-50
hours post injection). For safety assessment, a physical examination will be performed at
baseline and at the completion of all imaging to assess for interval change. An EKG and
vital signs will be obtained baseline, at each imaging time point to assess for interval
change. Blood will be drawn at baseline, and at each imaging time point to assess for
interval change in serum chemistries and complete blood count. Urine will be collected at
baseline and at each imaging time point to assess for interval change in urinalysis results.
The amount of radioactive tracer in the blood and urine will also be assessed on all 8 adult
normal volunteer subjects. One-mL blood samples will be obtained at baseline, 1, 2, 4, and
24 hours post Cu-25%CANF-Comb injection and prior to discharge. Urine will be collected
as a single accumulated collection over 24 hours immediately following injection of
Cu-25%CANF-Comb and prior to discharge.
Tracer biodistribution will be evaluated by measuring tracer uptake in various organs in the
torso on the PET-CT scan. The organs used to describe the biodistribution of the
radiopharmaceutical will be blood, liver, kidneys, spleen, heart, bone, muscle and other
organs showing significant uptake. Only organs and tissues containing a visible accumulation
of activity will be selected for image quantification. Region of Interests (ROIs) will be
drawn to measure average activity concentration in each organ or tissue. Values in
three-dimensional region of interest (3D-ROI) traced on the contour of the organs will be
used. For the large organs such as the liver, a large elliptical ROI encompassing as much of
the organ as possible will be used to obtain an average pixel value. To estimate bone
activity, a narrow, irregular ROIs will be drawn to approximate the visible cross section of
the ilium or large vertebrae, and the average pixel value will be used. For blood activity,
the average pixel intensity in a large 3D-ROI drawn over the left ventricle will be used,
thereby avoiding partial volume effects. Muscle activity will be taken as the average value
in a large elliptical ROI in the region of the buttocks as seen on MR images. Fat activity
will be taken as the average value in a large elliptical ROI in the region of the
subcutaneous abdominal fat. All other non-listed organ's activity concentration will be
measured in a similar fashion.
Residence times will be calculated by analytical integration of the fitted time taking into
account the radioactive decay of Cu. Residence times will be expressed in hours and
normalized to one unit injected activity. Blood activity will be also assigned to the heart,
lungs and bone marrow, organs for which activity will be not measured directly with an ROI.
The heart and lungs will be assigned a blood fraction based on their respective blood
volumes. Activity measured in bone is assigned half to cancellous bone and half to cortical
The percent injected dose values will be calculated by extrapolating the measured activity
concentration in each organ to the whole organ using standard organ and tissue volumes.
These standard volumes will be normalized to each patient's weight. Time activity curves
will be then constructed from these values for all organs for which ROIs were drawn
including liver, spleen, kidneys, bone, muscle blood pool and remainder of body by combining
the data from all the patients. The blood content of each organ will be included with the
organ where possible rather than assigning it uniformly to the remainder of body.
- Healthy volunteers (4 men and 4 women)
- No evidence of cardiovascular disease and not under care of a physician for any
active medical condition
- Health status confirmed by physical exam and ECG
- Signed informed consent
- Pregnancy or lactation
- Inability to lie still for up to 60 min with arms above head for PET-CT imaging
- Unwilling to comply with study procedures and unavailable for the duration of the
- Inability to provide written informed consent.