An open-label, multicenter, phase 2a study to assess the feasibility of imaging metastases in late-stage cancer patients with the alpha v beta 3-selective angiogenesis imaging agent 99mTc-NC100692.

BACKGROUND: The alpha(v)beta(3) integrin is one of the angiogenesis-related membrane proteins highly expressed on the neovasculature of breast cancer and lung carcinomas. Labeling of the alpha(v)beta(3) integrin with (99m)Tc-NC100692 provides a potential tool for imaging angiogenesis and hence the presence of malignant lesions. PURPOSE: To determine the feasibility of detecting metastatic lesions in liver, lung, bone, and brain with scintigraphy using the alpha(v)beta(3)-avid imaging agent (99m)Tc-NC100692 in patients with breast or lung cancer, and to assess its safety profile. MATERIAL AND METHODS: Twenty-five patients--15 with lung cancer and 10 with breast cancer--were recruited at 10 centers. Metastases were newly diagnosed by computed tomography, magnetic resonance imaging, or bone scintigraphy, i.e., the reference standard. Patients underwent whole-body scans of approximately 10-15 min duration beginning at 45 min post-injection and a SPECT acquisition of approximately 30 min beginning at 75 min after injection of up to 1100 MBq (99m)Tc-NC100692. In case of liver metastases, dynamic acquisitions of 15 min were performed starting immediately post-injection. Safety measurements were performed up to 2.5 hours after injection and included hematology, serum biochemistry, coagulation, urine analysis, vital signs, oximetry, 12-lead ECG assessments, and a physical examination. RESULTS: In patients with breast cancer, (99m)Tc-NC100692 scintigraphy detected 1 of 7 liver, 4 of 5 lung, 8 of 17 bone, and 1 of 1 brain metastases. The corresponding numbers for lung cancer patients were 0 of 2, 17 of 18, 2 of 2, and 7 of 9. There was overall stability through the follow-up period for all investigated safety parameters. CONCLUSION: Scintigraphy with (99m)Tc-NC100692 is feasible for detection of lung and brain metastases from breast and lung cancer, while the detection of liver and bone lesions is poor. The use of (99m)Tc-NC100692 is safe and well tolerated.

Relation of myocardial perfusion defects and nonsignificant coronary lesions by angiography with insights from intravascular ultrasound and coronary pressure measurements.

Several studies have demonstrated a correlation between myocardial ischemia and severity of coronary lesions as determined by intravascular ultrasound (IVUS) and fractional flow reserve (FFR) measurements. However, their value for the assessment of mild coronary stenoses that are associated with myocardial perfusion abnormalities has not been well studied. The objective of this study was to prospectively compare the results of myocardial perfusion as determined by exercise/dipyridamole myocardial single-photon emission computed tomography with IVUS and FFR measurements in patients who had angiographically mild coronary stenosis (< 50% diameter stenosis by quantitative coronary angiography). Forty-eight patients who had stable coronary disease (61 +/- 11 years of age; 6 women) were included. All had mild coronary stenosis in the proximal/middle segment of > or = 1 coronary artery and had undergone maximal exercise myocardial technetium-99m tetrofosmin single-photon emission computed tomography within 48 hours before coronary angiography. IVUS measurements included lesion lumen area, external elastic membrane area, lesion plaque burden (calculated as external elastic membrane minus lumen area, divided by external elastic membrane, and multiplied by 100), and lumen area stenosis (calculated as reference lumen area minus lesion lumen area, divided by reference lumen area, multiplied by 100). Fifty-three coronary lesions were studied, with a mean percent diameter stenosis of 34.9 +/- 7.9% on angiography. Myocardial perfusion defects were demonstrated by single-photon emission computed tomography in 11 patients (12 myocardial regions) with no differences in lesion percent diameter stenosis compared with those without perfusion defects. The presence of reversible perfusion defects was associated with a higher lesion plaque burden as evaluated by IVUS (67.4 +/- 8.1% vs 60.2 +/- 9.3%, p = 0.01). FFR values did not differ in the presence or absence of perfusion defects (0.90 +/- 0.06 vs 0.92 +/- 0.07, respectively; p = NS). In conclusion, plaque burden as determined by IVUS may partly explain the presence of myocardial perfusion defects in cases of angiographically nonsignificant coronary lesions. However, the high FFR values associated with these lesions suggest that other mechanisms, such as endothelial/microvascular dysfunction, might also account for perfusion abnormalities in these patients.