FDG-PET Imaging in Complicated Diabetic Foot

FDG-PET imaging is a promising imaging technique, which has the potential to overcome many of
the shortcomings mentioned previously with regard to radiologic and scintigraphic
methodologies. FDG is a diagnostic tracer utilized to measure the metabolic rates of normal
and abnormal tissues. Many investigators have noted the affinity of FDG for active
inflammatory and infectious disorders, such as sarcoidosis, the abdominal abscess, brain
abscess, lung abscess, renal abscess, inflammatory pancreatic disease, lobar pneumonia,
asthma, tuberculosis, colitis, sinusitis, myositis, mastitis, vasculitis, deep venous
thrombosis, thyroiditis and other infections including those encountered in orthopedic
patients.

According to the literature, the most accurate nuclear medicine modality for detecting
infection associated with diabetic foot is the labeled WBC method. We hypothesize that
FDG-PET imaging has several advantages over this method. Detection of infection by labeled
WBC imaging is based upon the assumption that the administered cells will migrate to the
sites of infection. Since the majority of the labeled leukocyte preparation consists of
neutrophils, inflammatory/infectious processes with a predominantly neutrophilic infiltrate
(acute infections) are likely to yield positive results. However, most infections associated
with diabetic foot are sub-acute or chronic. Consequently, the dominant inflammatory cells
involved are monocytes and lymphocytes. Therefore, labeled leukocytes are unlikely to detect
chronic infection since very few monocytes and lymphocytes are labeled. In addition, the
previous treatment (antibiotics, etc) can severely reduce the chemotropic effect of bacteria
and therefore, fewer leukocytes will migrate to the infectious sites, rendering the labeled
leukocyte method ineffective.

In contrast, the uptake of FDG in inflammatory cells reflects "in vivo labeling" of the
existing cells at the site of infection soon after the administration of the compound. This
would indicate that FDG-PET technique might allow imaging a substantially larger population
of cells, which are residing in the area of infection and inflammation. Therefore, in
addition to considerable simplification of procedures associated with the labeled WBC method,
including the time required to complete the study, this approach may provide higher
sensitivity for diagnosing infection in such settings. Furthermore, since FDG uptake does not
rely upon leukocyte migration, treatment with antibiotics is less likely to affect its
sensitivity in delineating the sites of infection. One possible advantage of the labeled WBC
method over FDG-PET imaging is that high serum glucose levels do not appear to have an
adverse effect on the test results with the former technique while hyperglycemia is known to
decrease tumor cell FDG uptake. However, our preliminary results indicate that high glucose
levels do not negatively affect FDG uptake by inflammatory cells. Based on these
observations, FDG-PET imaging appears to be an attractive alternative to conventional
techniques for the detection of infection.

FDG-PET imaging offers a unique tool for the diagnosis and management of the diabetic foot.
Through the establishment of appropriate diagnostic criteria, a PET scan may prove to be
highly accurate in localizing deep infections of bone and soft tissue associated with the
complicated diabetic foot. By distinguishing these infections from inflammation, it has the
potential to become the optimal diagnostic imaging technique with which to diagnose and
manage patients with diabetic foot. Therefore, research studies designed to further validate
the ability of this technique are essential to achieving this goal.

Inclusion Criteria:

- The 240 patients selected for entry into this study will be men or women of any ethnic
background diagnosed with diabetic foot disease by members of the team in the Diabetes
Center of the Department of Medicine and the division of Vascular Surgery of the
department of Surgery at the University of Pennsylvania Health System (Hospital of the
University of Pennsylvania).

Study I: FDG-PET imaging of patients with diabetic foot without clinical suspicion of
osteomyelitis or deep-seated tissue infections The patients must have clinical diagnosis of
uncomplicated diabetic foot. Each patient will undergo appropriate evaluation including
history, physical examination, standard radiographic evaluation (including MRI), and
grading of peripheral neuropathy using the Michigan Neuropathy Screening Instrument (MNSI).
Patients will be divided into three groups, corresponding to MNSI score of 0-3, 4-8, and
9-13, which we will classify as mild, moderate, and severe, respectively. We intend to
enroll 26 patients in each of the first two groups and 27 patients in the third.

Study II: FDG-PET imaging of patients with diabetic foot and clinical suspicion of
osteomyelitis or deep-seated infections The patients must have clinical diagnosis of
complicated diabetic foot. These patients will be those suspected of having a deep-seated
infection and may or may not be scheduled to undergo amputation or debridement of affected
tissue. Each patient will undergo an appropriate evaluation including history, physical
examination, radiologic examination including MRI, MNSI, and vascular assessment by
segmental Doppler pressures and pulse wave recording.

Exclusion Criteria:

- Patients with complications of the foot with etiologies not related to diabetes will
be excluded from this study.