Phase II study of treatment of advanced ovarian cancer with folate-receptor-targeted therapeutic (vintafolide) and companion SPECT-based imaging agent (99mTc-etarfolatide).

BACKGROUND: This report examines (99m)Tc-etarfolatide imaging to identify the presence of folate receptor (FR) on tumors of women with recurrent/refractory ovarian or endometrial cancer and correlates expression with response to FR-targeted therapy (vintafolide). PATIENTS AND METHODS: In this phase II, single-arm, multicenter study, patients with advanced ovarian cancer were imaged with (99m)Tc-etarfolatide before vintafolide treatment. Up to 10 target lesions (TLs) were selected based on Response Evaluation Criteria In Solid Tumors criteria using computed tomography scans. Single-photon emission computed tomography images of TLs were assessed for (99m)Tc-etarfolatide uptake as either FR positive or negative. Patients were categorized by percentage of TLs positive and grouped as FR(100%), FR(10%-90%), and FR(0%). Lesion and patient response were correlated with etarfolatide uptake. RESULTS: Forty-nine patients were enrolled; 43 were available for analysis. One hundred thirty-nine lesions were (99m)Tc-etarfolatide evaluable: 110 FR positive and 29 FR negative. Lesion disease control rate (DCR = stable or response) was observed in 56.4% of FR-positive lesions versus 20.7% of FR-negative lesions (P < 0.001). Patient DCR was 57%, 36%, and 33% in FR(100%), FR(10%-90%), and FR(0%) patients, respectively. Median overall survival was 14.6, 9.6, and 3.0 months in FR(100%), FR(10%-90%), and FR(0%) patients, respectively. CONCLUSIONS: Overall response to FR-targeted therapy and DCR correlate with FR positivity demonstrated by (99m)Tc-etarfolatide imaging. CLINICAL TRIAL NUMBER: NCT00507741.

Small solute clearance from the lungs of patients with cardiogenic and noncardiogenic pulmonary edema.

The regional clearance of 99mTc-diethylenetriamine penta-acetate (99mTc-DTPA) from the lungs was measured in 14 patients with noncardiogenic pulmonary edema, six patients with acute pulmonary edema secondary to heart failure, and 29 normal subjects. The radionuclide was delivered in an aerosol which was inhaled for 120 seconds, and the subsequent decline of radioactivity from the lungs was monitored for seven minutes over each of six peripheral regions of interest with a computerized scintillation camera. The average 99mTc-DTPA clearance of these regions was accelerated above the 98 percent confidence limits in all but three of the patients with noncardiogenic edema. The mean clearance value in this group of patients was significantly greater than those in normal subjects or patients with cardiogenic pulmonary edema. Clearances returned toward normal in each of seven subjects who improved clinically. Only one of the patients with cardiogenic pulmonary edema had an elevated average clearance rate, and the mean clearance for this population was not statistically greater than normal. This procedure appears to detect increased epithelial permeability caused by lung injury and may help distinguish between cardiogenic and noncardiogenic pulmonary edema.

Rapidly reversible alterations of pulmonary epithelial permeability induced by smoking.

A radioaerosol procedure using 99mcTc-DTPA (diethylene triamine penta acetate) was used to evaluate the permeability of the pulmonary epithelium in smokers and nonsmokers. The average clearance of this indicator from the lungs of smokers without significant airway obstruction exceeded that found in normal subjects by an average factor of more than five. This abnormality was observed throughout all lung regions. 99mTc-DTPA clearance decreased rapidly during the week after smoking was discontinued. It is concluded that smoking results in a rapidly reversible increase in pulmonary epithelial permeability.

Accelerated clearance of small solutes from the lungs in interstitial lung disease.

Solutions of 99mTc-diethylenetriaminepenta-acetate (99mTc-DTPA) and 99mTcO-4 were aerosolized and inhaled by subjects seated against a scintillation camera. Initial clearance rates of these radionuclides were determined over 6 posterior lung regions. Clearance of 99mTcO-4 (molecular weight, 163 dalton exceeded that of 99mTc-DTPA (molecular weight, 492 daltons) by an average factor of 3.3. Upper-lobe clearance of both radionuclides was greater than lower-lobe clearance in the normal subjects, but this gradient was abolished when the subjects exhaled against 7 cm of positive end-expiratory pressure. Twenty-one patients with clinical and roentgenographic evidence of interstitial lung disease (ILD) and diminished CO diffusion rates were studied with 99mTc-DTPA. Clearance of 99mTc-DTPA was increased in each of 5 patients with idiopathic pulmonary fibrosis, 4 of 8 with sarcoid, 2 of 5 with pneumoconiosis, and 2 of 3 patients with other forms of ILD. In contrast, the clearance of 99mTcO-4 was decreased in 4 patients with pulmonary alveolar proteinosis. Furthermore, no increase in 99mTc-DTPA clearance was found in 5 patients with chronic obstructive pulmonary disease. These studies suggest that the initial clearance of these aerosolized hydrophilic radionuclides is accomplished in part by diffusion through the epithelium of alveoli and respiratory bronchioles. Whereas radionuclide clearance is impaired by the presence of precipitated protein in these structures in pulmonary alveolar proteinosis, clearance is accelerated in ILD. This may indicate increased epithelial permeability in ILD related to injury and increased retractile forces.

Effects of maximal exercise stress on left ventricular function in patients with coronary artery disease using first pass radionuclide angiocardiography: a rapid, noninvasive technique for determining ejection fraction and segmental wall motion.

Angiographically determined changes in segmental wall motion (SWM) and ejection fraction (EF) are sensitive indices of left ventricular (LV) function. To compare the effects of exercise on LV function, first pass radionuclide angiocardiography was used before and during maximal upright bicycle stress in patients with nonsignificantly stenosed coronary arteries, and in those with greater than 75% stenosis. Gamma camera acquisitions were made in the 30 degree RAO projection using a 20 mCi I.V. bolus of 99mTc-pertechnetate. In the control group (seven normals, one nonsignificant (CAD) the EF significantly increased between rest and exercise (0.65 +/- 0.03 to 0.81 +/- 0.03 (mean +/- SEM), p less than 0.005). In this group SWM measured over the two anterior and two inferoposterior segments uniformly increased. In the 11 patients with a history of angina and significant coronary artery obstruction, the EF did not change in three and significantly decreased in the remaining eight (0.57 +/- 0.04 to 0.45 +/- 0.03, p less than 0.005). In all 11 patients SWM either decreased or did not increase in the areas supplied by the significantly stenosed coronary arteries. Upright maximal stress angiocardiography appears to be well-suited for diagnosing ischemic heart disease and localizing the area of ischemic dysfunction.

Liver metastases of oat cell carcinoma of lung detected on 99mTc-diphosphonate bone scan.

Colon carcinoma, cholangiocarcinoma, malignant melanoma and liver metastases detected on bone imaging have been reported with different bone seeking radiopharmaceuticals. This report is concerned with an interesting case of oat cell carcinoma with hepatic metatases visualized on 99mTc-diphosphonate bone imaging. This has not been previously reported.

Diagnosis of uveo-parotid fever by 67Ga-citrate imaging.

67Ga-citrate scan from skull to mid-abdomen showed increased uptake in both parotid glands, mediastinum, lungs, uvei and/or enlarged lacrimal glands. The differential diagnosis of the positive radiogallium scan is discussed with emphasis on the value of the extrathoracic findings. Tissue diagnosis confirmed the imaging diagnosis of sarcoidosis. The case illustrates the usefulness of double radionuclide study--67Ga and 99mTc-MAA--and of the tomographic scanner in defining the spread of the active granulomatous disease.

Dynamic imaging of the systemic perfusion of a lung cancer: case report.

Dynamic lung circulation scintigraphy employing intravenously administered 99mTc as pertechnetate was used to visualize the pulmonary arterial and systemic arterial circulations in a patient with bronchogenic carcinoma. Computer-processed dynamic images and region-of-interest data were utilized to demonstrate differences between tumor and normal regions regarding pulmonary and systemic blood supplies.

Liver scan "hot spot" in hepatic veno-occlusive disease.

A focal "hot spot" seen on liver scan in an unusual case of hepatic veno-occlusive disease bore striking similarities to scanning patterns in superior vena cava syndrome. The findings are also compared to those reported in Budd-Chiari syndrome.