Positron emission tomography imaging for herpes virus infection: Implications for oncolytic viral treatments of cancer.

Molecular therapy using viruses would benefit greatly from a non-invasive modality for assessing dissemination of viruses. Here we investigated whether positron emission tomography (PET) scanning using [(124)I]-5-iodo-2'-fluoro-1-beta-d-arabinofuranosyl-uracil (FIAU) could image cells infected with herpes simplex viruses (HSV). Using replication-competent HSV-1 oncolytic viruses with thymidine kinase (TK) under control of different promoters, we demonstrate that viral infection, proliferation and promoter characteristics all interact to influence FIAU accumulation and imaging. In vivo, as few as 1 x 107 viral particles injected into a 0.5-cm human colorectal tumor can be detected by [(124)I]FIAU PET imaging. PET signal intensity is significantly greater at 48 hours compared with that at 8 hours after viral injection, demonstrating that PET scanning can detect changes in TK activity resulting from local viral proliferation. We also show the ability of FIAU-PET scanning to detect differences in viral infectivity at 0.5 log increments. Non-invasive imaging might be useful in assessing biologically relevant distribution of virus in therapies using replication-competent HSV.

Development and application of normal limits for left ventricular ejection fraction and volume measurements from 99mTc-sestamibi myocardial perfusion gates SPECT.

UNLABELLED: Gated SPECT is a reproducible method for assessing left ventricular volume (LVV) and left ventricular ejection fraction (LVEF) from 99mTc-sestamibi myocardial perfusion imaging studies. LVV and LVEF measurements by this approach correlate well with those obtained from other cardiovascular imaging techniques. Nevertheless, the lack of criteria for abnormal test findings has limited the potential clinical application of this new imaging technique. METHODS: Gated SPECT measurements were evaluated for 214 patients with a low Bayesian likelihood (< 10%) of coronary artery disease (CAD) before performance of 99mTc-sestamibi stress-rest myocardial perfusion SPECT. The patients were grouped into normotensive patients (n = 98), hypertensive patients without left ventricular hypertrophy (LVH) (n = 80), and hypertensive patients with LVH on resting electrocardiography (n = 36). Gated SPECT measurements for left ventricular end-diastolic volume (LVEDV) index, left ventricular end-systolic volume (LVESV) index, and LVEF were obtained according to a published method, using a modified Simpson's rule technique. RESULTS: Similar results were obtained for mean LVV and LVEF measurements between normotensive patients and hypertensive patients without LVH. Hence, these groups were combined (as group 1). By contrast, hypertensive patients with LVH (group 2), had significantly lower LVEF values (P = 0.01) and higher mean LVESV index values than normotensive patients (P = 0.03). Sex differences were marked: women had significantly higher mean resting LVEF values than men (P < 0.0001) and significantly lower mean resting LVEDV index values (P < 0.0001). A significant relationship was seen between LVEDV index and LVEF (r = -0.60; P < 0.0001) and between LVEDV index and heart rate (r = -0.26; P < 0.001). The normal limits were LVEF > or = 41% in men and > or = 49% in women, LVEDV index < or = 76 mL/m2 in men and < or = 57 mL/m2 in women, and LVESV index < or 38 mL/m2 in men and < or =26 mL/m2 in women. Among hypertensive patients, 22% with LVH had an abnormally low LVEF and 19% had an increased LVEDV index according to these test criteria. By contrast, no hypertensive patients without LVH had an abnormally low LVEF, and only 6% had volume abnormalities. CONCLUSION: Using a cohort of low-likelihood patients, we generated sex-specific normal limits for LVV and LVEF for myocardial perfusion gated SPECT. Application of these findings resulted in the detection of occult left ventricular dysfunction in approximately one fifth of hypertensive patients for whom concomitant LVH was found through resting electrocardiography. These normal limits can now be evaluated prospectively for their potential clinical value.