Vassilios Papantoniou

Imaging in situ breast carcinoma (with or without an invasive component) with technetium-99m pentavalent dimercaptosuccinic acid and technetium-99m 2-methoxy isobutyl isonitrile scintimammography.

IntroductionThe aim of the study was to retrospectively define specific features of the technetium-99m pentavalent dimercaptosuccinic acid (99mTc-(V)DMSA) and technetium-99m 2-methoxy isobutyl isonitrile (99mTc-Sestamibi [99mTc-MIBI]) distribution in ductal breast carcinoma in situ and lobular breast carcinoma in situ (DCIS/LCIS), in relation to mammographic, histological and immunohistochemical parameters.Materials and methodsOne hundred and two patients with suspicious palpation or mammographic findings were submitted preoperatively to scintimammography (a total of 72 patients with 99mTc-(V)DMSA and a total of 75 patients with 99mTc-Sestamibi, 45 patients receiving both radiotracers). Images were acquired at 10 min and 60 min, and were evaluated for a pattern of diffuse radiotracer accumulation. The tumor-to-background ratios were correlated (T-pair test) with mammographic, histological and immunohistochemical characteristics.ResultsHistology confirmed malignancy in 46/102 patients: 20/46 patients had DCIS/LCIS, with or without coexistent invasive lesions, and 26/46 patients had isolated invasive carcinomas. Diffuse 99mTc-(V)DMSA accumulation was noticed in 18/19 cases and 99mTc-Sestamibi in 6/13 DCIS/LCIS cases. Epithelial hyperplasia demonstrated a similar accumulation pattern. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value for each tracer were calculated. Solely for 99mTc-(V)DMSA, the tumor-to-background ratio was significantly higher at 60 min than at 10 min and the diffuse uptake was significantly associated with suspicious microcalcifications, with the cell proliferation index ≥ 40% and with c-erbB-2 ≥ 10%.Conclusion99mTc-(V)DMSA showed high sensitivity and 99mTc-Sestamibi showed high specificity in detecting in situ breast carcinoma (99mTc-(V)DMSA especially in cases with increased cell proliferation), and these radiotracers could provide clinicians with preoperative information not always obtainable by mammography.

Uptake and washout of 99mTcV-dimercaptosuccinic acid and 99mTc-sestamibi in the assessment of histological type and grade in breast cancer

This study was performed to investigate the relationship between histological type and grade, with the uptake and washout of 99mTc-hexakis-2-methoxyisobutylisonitrile (99mTc-sestamibi, 99mTc-MIBI) and 99mTcV-dimercaptosuccinic acid (99mTcV-DMSA) in breast cancer. Forty-five patients with histologically proven breast cancer had previously been referred for 99mTcV-DMSA and/or 99mTc-MIBI scintimammography. Twenty-five of them underwent both 99mTcV-DMSA and 99mTc-MIBI scintigraphy in a double phase study. Lateral prone and anterior supine images were acquired at 15 and 60 min after administration of 740-925 MBq of each radiotracer. Uptake ratios and retention index were calculated and correlated with histology and grade of malignancy. Histology showed eight different histotypes: 77.7% were infiltrating ductal or lobular carcinomas. Mammography was definitely positive in 32/45, indeterminate in 10 and negative in three cases (sensitivity 71%). 99mTcV-DMSA was true positive in 37/40 (sensitivity 92.5%) and 99mTc-MIBI in 28/30 (sensitivity 93.3%) breast cancers. Uptake ratios were significantly higher in ductal than in lobular carcinomas on 99mTcV-DMSA and 99mTc-MIBI scintigrams at early and delayed phases. Grade II carcinomas had significantly lower values of retention index (rapid washout) than grade III carcinomas. This finding was statistically significant only on 99mTc-MIBI scans and was observed in ductal and lobular carcinomas. The retention index did not show any significant difference between ductal and lobular carcinomas. Uptake ratios were also not statistically different between grade II and III cancers. It is concluded that 99mTc-MIBI and 99mTcV-DMSA uptake in breast cancer is probably related to histological type and may distinguish ductal from lobular carcinomas. To a certain degree, the washout rate may reflect the histological grade, but since grade is not the only factor influencing this phenomenon it should be explored further in conjunction with other parameters by multivariate analysis in order to clarify eventual indirect correlations.

Increased Breast Density Correlates with the Proliferation- Seeking Radiotracer 99m Tc(V)-DMSA Uptake in Florid Epithelial Hyperplasia and in Mixed Ductal Carcinoma In Situ with Invasive Ductal Carcinoma but Not in Pure Invasive Ductal Carcinoma or in Mild Epithelial Hyperplasia

The purpose of this study was to assess the relationship of mammographic breast density (BD) and cell proliferation/focal adhesion kinase activation–seeking radiotracer technetium 99m pentavalent dimercaptosuccinic acid (99mTc(V)-DMSA) uptake in women with different breast histologies, that is, mild epithelial hyperplasia (MEH), florid epithelial hyperplasia (FEH), mixed ductal carcinoma in situ with invasive ductal carcinoma (DCIS + IDC), and pure IDC. Fifty-five women with histologically confirmed mammary pathologies were submitted preoperatively to mammography and 99mTc(V)-DMSA scintimammography. The percentage and intensity of 99mTc(V)-DMSA uptake and the percentage of BD were calculated by computer-assisted methods and compared (t-test) between the breast pathologies. In breasts with increased BD, FEH and DCIS + IDC were found. On the contrary, pure IDC and MEH were identified in breasts with significantly lower BD values. In breasts with increased 99mTc(V)-DMSA area and intensity of uptake, FEH was the main lesion found compared to all other histologies. Linear regression analysis between BD and 99mTc(V)-DMSA uptake area and intensity revealed significant coefficients of correlation (r = .689, p < .001 and r = .582, p < .001, respectively). Increased BD correlates with the presence of FEH and mixed DCIS + IDC but not with pure IDC or MEH. Its close relationship to 99mTc(V)-DMSA, which also showed an affinity to FEH, indicates that stromal microenvironment may constitute a specific substrate leading to progression to different subtypes of cancerous lesions originating from different pathways.

Tc-99m depreotide imaging of I-131-negative recurrent metastatic papillary thyroid carcinoma

The detection of radioiodine (I‐131)‐negative metastases of differentiated thyroid carcinoma (DTC) has been hitherto successfully tried by the well‐known synthetic somatostatin analogue indium‐111‐labeled DTPA‐octreotide (In‐111 pentetreotide). The objective of this study was to evaluate the usefulness of scintiscan with the newer synthetic somatostatin analogue Tc‐99m depreotide, in the restaging of papillary thyroid carcinoma (PTC) with detectable serum thyroglobulin (Tg) levels and negative I‐131 whole‐body scan (WBS). Whole‐body planar and cervico‐thoracic tomographic scintigraphy (single‐photon emission tomography—SPET) with Tc‐99m depreotide was performed in a 68‐year‐old male patient suffering from PTC stage III, with a mild increase in serum Tg levels coupled with a recent negative I‐131 WBS. The findings were compared with those of neck ultrasonography (US) and computerized tomography (CT). Nodal neck dissection and histopathology provided the definitive diagnosis. Tc‐99m depreotide scanning revealed foci of cervical lymph node metastases, which did not accumulate I‐131. The findings were in accordance with neck US and CT. Histopathology established the diagnosis of metastatic cervical lymph node PTC. Lymph node immunoreactivity was positive for the somatostatin receptor subtypes 2, 5 and 3. Scintigraphy with Tc‐99m depreotide could prove a useful adjunct to the armamentarium for the follow‐up of PTC, especially in the setting of detectable serum Tg and negative I‐131 WBS.

Renin-angiotensin system dysregulation in fetuses with hydronephrosis

OBJECTIVES To evaluate if fetal hydronephrosis is associated with dysregulation of the renin-angiotensin system (RAS), and if it could represent an early predictor of future renal damage or arterial hypertension. STUDY DESIGN The study consisted of 26 pregnant women and their fetuses. Ultrasound scans were performed to evaluate the renal pelvis in fetuses. Four fetuses with hydronephrosis were included in the study, while the rest were found to have normal renal pelvis. Active and inactive renin was calculated by IRMA method in fetal and maternal blood, during the second trimester of pregnancy. RESULTS A comparison of plasma active and inactive renin levels was made between pregnant women and their fetuses, as well as between fetuses with and without hydronephrosis. Active and inactive renin levels obtained from fetuses with hydronephrosis were significantly higher compared to those obtained from fetuses with normal kidneys. CONCLUSIONS Dilatation of renal pelvis in the second trimester of pregnancy seems to up-regulate the renin and prorenin system in fetal blood. Both factors are indicative of possible future renal pathology.

Ibuprofen Induces Reduction of the Proliferation-Seeking Radiotracer 99mTc-(V)DMSA Uptake in Severe Epithelial Breast Hyperplasia without Atypia

The purpose of this study was to investigate if ibuprofen intake can influence mammary uptake of the proliferation-seeking radiotracer technetium 99m–pentavalent dimercaptosuccinic acid (99mTc-(V)DMSA) in women with severe epithelial and atypical epithelial breast hyperplasia. Eight patients with histologically confirmed severe epithelial breast hyperplasia with (n = 4) and without atypia (n = 4) were submitted prospectively to 99mTc-(V)DMSA scintimammography before and after a 4-week course of 400 mg ibuprofen daily oral intake. Lesion to background ratios 60 minutes postinjection were calculated and compared (t-test) before and after ibuprofen administration. Prior to ibuprofen, the patients with severe epithelial hyperplasia displayed a significantly higher 99mTc-(V)DMSA uptake ratio compared to those with atypical epithelial hyperplasia (2.40 ± 0.32 vs 1.67 ± 0.09, respectively; p = .003). They also exhibited a more substantial percent decline in tracer uptake postibuprofen compared to women with atypical epithelial hyperplasia (62.0 ± 7.1 vs 15.0 ± 0.2, respectively; p = .001). Ibuprofen induces significant uptake reduction of the proliferation-seeking radiotracer 99mTc-(V)DMSA in severe epithelial breast hyperplasia without atypia. This agent could therefore constitute a potential imaging tool for monitoring chemoprophylaxis effectiveness in women at the early stages of malignant transformation.

Scintimammography - Molecular Imaging: Value and New Perspectives with 99mTc(V)-DMSA

Breast cancer is the most common non-skin cancer and the second leading cause of cancer death in women. Despite advances in the adjuvant treatment of early stage disease, many women will have breast cancer relapse that often is not amenable to complete surgical excision [Eubank et al., 2005]. There are 40,000 women per year dying of breast cancer in the United States, and most breast cancer victims die of progressive metastatic disease.

Reduced uptake of the proliferation-seeking radiotracer technetium-99m-labelled pentavalent dimercaptosuccinic acid in a 47-year-old woman with severe breast epithelial hyperplasia taking ibuprofen: a case report

IntroductionRecent studies have reported a risk reduction in the progression of benign breast disease to breast carcinoma through COX-2 pathways.Case presentationWe present a case of severe epithelial hyperplasia in a 47-year-old woman with increased breast density submitted to scintimammography by the proliferation-imaging tracer Technetium-99m-labelled pentavalent dimercaptosuccinic acid, before and after an oral ibuprofen treatment for 4 weeks. The radiotracer uptake after ibuprofen intake was significantly reduced, both visually and by semi-quantitative analysis, based on a calculation of lesion-to-background ratios.ConclusionIn proliferating breast lesions, scintigraphically displayed reduction in Technetium-99m-labelled pentavalent dimercaptosuccinic acid uptake may indicate inhibition by ibuprofen in the pathway of malignant epithelial cell transformation.

Abstract 2381: Neoangiogenesis correlates with increased breast density, calcitonin gene related peptide positivity and cell proliferation seeking radiotracer uptake in mixed invasive ductal associated with in situ, but not in pure invasive breast carcinoma

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Aim: To assess neoangiogenesis in relation to breast density (BD), calcitonin gene related peptide (CGRP), cell proliferation seeking radiotracer 99mTc-(V)DMSA uptake (SMM) in invasive ductal associated with extensive in situ carcinoma (DCIS + IDC) and in pure invasive breast carcinoma (IDC). Methods: 20 patients with histologically confirmed mixed DCIS + IDC (n=10) and pure IDC (n=10) were submitted preoperatively to mammography and scintimammography. The percentage of breast density (BD) and the percentage of tracer uptake (SMM) were calculated with computer assisted methods. CGRP and the number of newly formed blood vessels (NBV) were immunohistochemicaly assessed. NBV, BD, CGRP, and SMM were compared (t-test) between the two groups. Linear regression analysis was performed between NBV, BD, CGRP and SMM in both groups. Results: NBV, BD, CGRP and SMM were significantly higher in mixed DCIS + IDC as compared to pure IDC (32.1±10.4 vs 24.3±5 p=0.048, 35.2 ± 6.9 vs 25.6±10.7 p=0.028, 25.5±7.6 vs 17±7.8 p=0.024, 26.75±4.09 vs 11.34±8.5 p=0.0009). NBV was strongly correlated with BD and CGRP in the DCIS component of the mixed group (r=0.933 p<0.001, r=0.793 p<0.01 respectively). BD was also significantly correlated with CGRP and SMM in the DCIS component of the same group (r=0.974 p<0.001, r=0.728 p<0.05 respectively). In contrast, no significant correlation(NS) was found between NBV and BD, CGRP or between BD and CGRP, SMM in both the IDC component of mixed group and pure IDC group (r=0.388 NS, r=0.391 NS, r= − 0.597 NS, r= − 0.352 NS in the IDC component of mixed group; r=0.584 NS, r= 0.297 NS, r= − 0.574 NS, r= −0.294 NS in pure IDC respectively). Conclusion: Mixed DCIS + IDC lesions exhibit significantly increased NBV, BD, CGRP and SMM values as compared to those of IDC lesions. The strong correlation between neoangiogenesis and the other parameters in the mixed group indicates that the mixed DCIS + IDC constitutes a strictly different entity from pure IDC, more aggressive and probably originates from the stroma through the CGRP pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2381.