RESUMO
INTRODUCTION: Tumors over-expressing the human epithelial receptor 2 (HER2) or exhibiting amplification or mutation of its proto-oncogene have a poorer prognosis. Using trastuzumab and/or other HER2 targeted therapies can increase overall survival in patients with HER2(+) tumors making it critical to accurately identify patients who may benefit. We report on a Phase 0 study of the imaging agent, 111In-CHX-A"-DTPA trastuzumab, in patients with known HER2 status to evaluate its safety and biodistribution and to obtain preliminary data regarding its ability to provide an accurate, whole-body, non-invasive means to determine HER2 status. METHODS: 111In-CHX-A"-DTPA trastuzumab was radiolabeled on-site and slowly infused into 11 patients who underwent single (n=5) or multiple (n=6) ɣ-camera (n=6) and/or SPECT (n=8) imaging sessions. RESULTS: No safety issues were identified. Visual and semi-quantitative imaging data were concordant with tissue HER2 expression profiling in all but 1 patient. The biodistribution showed intense peak liver activity at the initial imaging timepoint (3.3h) and a single-phase clearance fit of the average time-activity curve (TAC) estimated t1/2=46.9h (R2=0.97; 95%CI 41.8 to 53h). This was followed by high gastrointestinal (GI) tract activity peaking by 52h. Linear regression predicted GI clearance by 201.2h (R2 =0.96; 95%CI 188.5 to 216.9h). Blood pool had lower activity with its maximum on the initial images. Non-linear regression fit projected a t1/2=34.2h (R2 =0.96; 95%CI 25.3 to 46.3h). Assuming linear whole-body clearance, linear regression projected complete elimination (x-intercept) at 256.5hr (R2=0.96; 95%CI 186.1 to 489.2h). CONCLUSION: 111In-CHX-A"-DTPA trastuzumab can be safely imaged in humans. The biodistribution allowed for visual and semiquantitative analysis with results concordant with tissue expression profiling in 10 of 11 patients. Advances in Knowledge and Implications for Patient Care Using readily available components and on-site radiolabeling 111In-CHX-A"-DTPA trastuzumab SPECT imaging may provide an economical, non-invasive means to detect HER2 over-expression.
RESUMO
BACKGROUND: Z-endoxifen is the most potent of the metabolites of tamoxifen, and has the potential to be more effective than tamoxifen because it bypasses potential drug resistance mechanisms attributable to patient variability in the expression of the hepatic microsomal enzyme CYP2D6. 18F-FES is a positron emission tomography (PET) imaging agent which selectively binds to estrogen receptor alpha (ER-α) and has been used for non-invasive in vivo assessment of ER activity in tumors. This study utilizes 18F-FES PET imaging as a pharmacodynamic biomarker in patients with ER+ tumors treated with Z-endoxifen. METHODS: Fifteen patients were recruited from a parent therapeutic trial of Z-endoxifen and underwent imaging with 18F-FES PET at baseline. Eight had positive lesions on the baseline scan and underwent follow-up imaging with 18F-FES 1-5 days post administration of Z-endoxifen. RESULTS: Statistically significant changes (p = 0.0078) in standard uptake value (SUV)-Max were observed between the baseline and follow-up scans as early as 1 day post drug administration. CONCLUSION: F-FES PET imaging could serve as a pharmacodynamic biomarker for patients treated with ER-directed therapy.
Assuntos
Neoplasias da Mama Masculina/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Estradiol/análogos & derivados , Neoplasias dos Genitais Femininos/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama Masculina/tratamento farmacológico , Neoplasias da Mama Masculina/genética , Antagonistas de Estrogênios/uso terapêutico , Feminino , Neoplasias dos Genitais Femininos/tratamento farmacológico , Neoplasias dos Genitais Femininos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Estrogênio/antagonistas & inibidores , Receptores de Estrogênio/genética , Tamoxifeno/análogos & derivados , Tamoxifeno/uso terapêuticoRESUMO
BACKGROUND: A nonischemic electrocardiogram (ECG) in association with myocardial infarction (MI) indicates a small MI in some but not all cases. Myocardial perfusion imaging using technetium-99m sestamibi offers the ability to better characterize these "electrically silent" infarctions. METHODS: Patients considered low risk for myocardial infarction with a normal or nonischemic ECG (no significant ST elevation, ST depression, ischemic T-wave inversion, or left bundle branch block) underwent early emergency department perfusion imaging, followed by serial myocardial marker sampling. Risk area (defect size) was quantitated by use of a 50% threshold from multiple short-axis slices. RESULTS: A total of 87 patients with nonischemic ECGs had myocardial infarction (mean peak creatine kinase [CK] 710 +/- 720 U/L, range 111-3196 U/L). Peak CKs were lower in the 7 patients with negative perfusion imaging (420 +/- 290 U/L vs 730 +/- 740 U/L, P =.06). Mean risk area was 18% +/- 11% of the left ventricle (range 0%-62%) and was not significantly different among the different infarct-related arteries. Patients with normal ECGs had a similar risk area compared with other patients (16% +/- 12% vs 19 +/- 12%, P =.25). Coronary angiography was performed in 81 patients, with significant stenoses in 74 (91%) (37 one-vessel, 19 two-vessel, 18 three-vessel), with the infarct related artery most commonly the left circumflex (n = 32 [38%]). CONCLUSIONS: The ischemic risk area in patients with a nonischemic ECG was comparable to patients with inferior ST-elevation myocardial infarction found in previous studies. A nonischemic ECG does not predict a small ischemic risk area.
Assuntos
Eletrocardiografia , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/diagnóstico , Compostos Radiofarmacêuticos , Tecnécio Tc 99m Sestamibi , Angiografia Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cintilografia , Medição de RiscoAssuntos
Citratos , Radioisótopos de Gálio , Gálio , Aparelho Lacrimal/diagnóstico por imagem , Nasofaringe/diagnóstico por imagem , Glândula Parótida/diagnóstico por imagem , Compostos Radiofarmacêuticos , Animais , Diagnóstico Diferencial , Humanos , Cintilografia , Sarcoidose/diagnóstico por imagem , UrsidaeRESUMO
BACKGROUND AND PURPOSE: The complex information obtained by CT, MR, and ultrasound examinations is often difficult to convey with a written report. Today's multimedia computer technology provides a medium within which the audio and the visual components of a radiologic consultation can be made available simultaneously, with the projected capability of remote access from any personal computer. A system was developed to run on low-end computer systems with image quality adequate for reporting purposes and prudent memory management (each report occupies < 4 MB). With this system-"Robo-Rad"-the image and radiologist are recorded simultaneously while he or she describes and points out (with a mouse) areas of interest. This dynamic report, along with patient data, can be retrieved and viewed by the consulting physician at his/her convenience using a low-end PC or Macintosh computer. MATERIALS AND METHODS: To assess the clinical utility of Robo-Rad, survey responses were solicited from clinical physicians at the Penn State University Hospital (41.5% faculty/fellows, 31.7% residents, 11.8% medical students, 2% clinical nursing; n = 101) during a hands-on demonstration using studies of 35 consecutive inpatients whose CT scans had been dictated into the system. RESULTS: In an average week, the surveyed professionals ordered 3.2 +/- 3.0 CT studies, reviewed 3.8 +/- 3.0 CTs, spent 1.5 +/- 2.0 hours locating Ct studies, and discussed 2.3 +/- 1.9 CT cases with a radiologist. The average time spent discussing a single CT case with a radiologist was reported as 9.4 +/- 5.9 minutes. On a five-point rating scale (1 = not at all to 5 = very much so), respondents indicated that the Robo-Rad report was helpful (4.3 +/- 0.7) and provided clinically important information that would be difficult to convey with current dictation systems (4.2 +/- 0.8). Desire to discuss the case with a radiologist in addition to viewing the Robo-Rad report scored 3.2 +/- 1.0. If such a system were readily available, 91.8% of the respondents indicated that they would use it in addition to the currently available written report and audio dictation system, and 96.6% would use it instead of the current system. Local area network and modems were the modalities of highest interest for remote access (69.3% and 44.6%, respectively). CONCLUSIONS: Judging by these data, the Robo-Rad system would be of benefit to clinicians. It provides a user-friendly, low-cost multimedia radiology report utilizing readily available technology to improve radiologist-clinician communication.