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Biomedical subjects

S Del Vecchio

Publications and source records attributed to S Del Vecchio.

At least 19 recordsLinked to original sources
PubMed2005

Poorly differentiated small cell neuroendocrine carcinoma localized in three different endocrine glands: response to chemotherapy and octreotide LAR.

Neuroendocrine tumors represent a heterogeneous category of neoplasm, with conflicting diagnostic and therapeutic demands. We here describe the case of a 72-yr-old woman with evidence of a poorly differentiated small-cell neuroendocrine carcinoma (NEC) localized in different endocrine glands and other non-endocrine organs. In particular, a large ovarian mass, multinodular thyroid goiter, right adrenal mass, cystic liver metastases and anterior mediastinum lymph node metastasis were present. The largest thyroid nodule caused tracheal restriction and dyspnea. Diagnosis of poorly differentiated metastasized NEC of unknown origin was made on the basis of histological and immunohistochemical findings, and treatment with etoposide (100 mg/m2 in days 1, 2 and 3) and cisplatinum (45 mg/m2 in days 2 and 3) was initiated. Simultaneously, im administration of octreotide LAR 20 mg every 28 days was started, according to the presence of SS receptors at 111In-octreotide scan. Rapid improvement of dyspnea and a reduction of the largest thyroid nodule, liver metastases and adrenal mass by 50% were observed after 3 months of treatment; the dimensions remained stable thereafter, while the pericardial lymph node disappeared. In conclusion, poorly differentiated NEC of unknown primary site is a well-recognized category, usually with an aggressive behavior, rapid growth rate and wide dissemination. Median survival of these patients is 6 months if left untreated. Our patient is alive 18 months after beginning the treatment, reporting good general condition and quality of life over the whole follow-up period.

Adrenal Gland Neoplasms↗
PubMed2005

Washout of [99mTc] sestamibi in predicting response to chemotherapy in patients with multiple myeloma.

AIM: Technetium-99m 2-methoxy-isobutyl-isonitrile ([99mTc] MIBI) has been successfully used to study patients with multiple myeloma (MM). This tracer is also a substrate for P-glycoprotein (Pgp). Since Pgp overexpression is one of the primary mechanisms of multidrug resistance in MM, the aim of this study was to test whether [99mTc] MIBI could be an index of Pgp overexpression and function in MM and therefore predicts response to chemotherapy. METHODS: Forty patients with MM (12 in stage I, 15 in stage II, and 13 in stage III) showing diffuse bone marrow [99mTc] MIBI uptake were included in the study. All patients underwent whole body scintigraphy at 10 and 60 minutes after i.v. injection of 555 MBq of [99mTc] MIBI. [99mTc] MIBI washout was measured, after decay correction, as: (10 minute counts/pixel minus 60 minute counts/pixel) divided by 10 minute counts/pixel, computed on a region of interest drawn on the thoracic spine (posterior projection), taking care of avoiding heart and splanchnic organs. Disease restaging was performed at a mean time of 32+/-20 months, and patients were considered to be in remission (complete or partial) or to show disease progression on the basis of a complete clinical and hematological evaluation. RESULTS: Patients showing disease progression at restaging (n=26) had higher washout (19.3+/-9.8% vs 12.8+/-6.9%, p<0.05) than patients in remission (n=14). Disease free survival was significantly better in patients with lower washout of [99mTc] MIBI. No differences in therapeutic regimen and stage of disease at admission were found between the 2 groups. When patients treated with melphalan were excluded from the analysis, 87.5% of patients in remission had low washout. CONCLUSIONS: The present study suggests a potential role of [99mTc] MIBI washout in predicting response to chemotherapy in patients with MM.

Antineoplastic Agents↗
PubMed2004

In vitro and in vivo characterization of Indium-111 and Technetium-99m labeled CCK-8 derivatives for CCK-B receptor imaging.

Cholecystokinin (CCK) receptors of the subtype B (CCK-BR) have been shown to be overexpressed in certain neuroendocrine tumors including medullary thyroid cancer. Our recent work has focused on new methods to radiolabel the CCK8 peptide with 111In or 99mTc for CCK-B receptor imaging. Derivatives of CCK8 were obtained by addition at the N-terminus in solid phase of a DTPA derivative (DTPAGlu) linked through a glycine spacer (DTPAGlu-G-CCK8) or cysteine, glycine and a diphenylphosphinopropionyl moiety (PhosGC-CCK8) for labeling with 111In and 99mTc, respectively. CCK-BR overexpressing A431 cancer cell lines were utilized to characterize in vitro properties of the two compounds as well as for generating xenografts in nude mice for in vivo characterization. Both 111In-DTPAGlu-G-CCK8 and 99mTcPhosGC-CCK8 showed similar binding affinities for CCK-BR with dissociation constants of 20-40 nM, were internalized after interaction with the receptor and displayed prolonged cellular retention times. Specific in vivo interaction with the receptor of both CCK8 analogs was observed in our animal model. 111In-DTPAGlu-G-CCK8 showed better target to non-target ratios, although it appeared to be rapidly metabolized after injection and activity cleared through the kidneys. 99mTc-PhosGC-CCK8 was more stable in vivo but showed marked hepatobiliary clearance with resulting high background activity in the bowel. The rapid clearance and lower background obtained with 111In-DTPAGlu-G-CCK8 make this a better candidate for further development.

Animals↗
PubMed2003

MIBI as prognostic factor in breast cancer.

Evaluation of treatment response is of primary importance in the management of patients with cancer. Both positron- and g-emitting compounds have been used to monitor changes in tumor metabolism or viability after therapy. The use of (99m)Tc-labeled lipophilic cations raised the possibility to predict the tumor response to treatment and to identify patients who will become refractory to subsequent therapy. In particular, many studies have shown the prognostic value of (99m)Tc-MIBI scan in different types of malignancy including breast and lung cancer, lymphoma and sarcoma. The ability of (99m)Tc-MIBI to interact with P-glycoprotein, allowing the functional assessment of the multidrug resistant phenotype, is one of the mechanisms underlying its prognostic value. Additional mechanisms of cell resistance, mainly involving alterations of apoptosis, may affect (99m)Tc-MIBI uptake in tumors. Therefore, either an enhanced tracer clearance or a reduced early uptake of (99m)Tc-MIBI indicate a poor response to therapy. In both cases, (99m)Tc-MIBI scan may ensure that the further management strategy will be effective in individual cancer patients.

Breast Neoplasms↗
PubMed2002

Radiolabeling approaches for cholecystokinin B receptor imaging.

Regulatory peptides and their analogs are being extensively investigated as radiopharmaceuticals for cancer imaging. In particular, cholecystokinin (CCK) receptors of the subtype B (CCK-BR) have been shown to be overexpressed in certain neuroendocrine tumors including medullary thyroid cancer. Our recent work has focused on new methods to radiolabel the CCK8 peptide with (111)In or (99m)Tc for the purpose of developing radiopharmaceuticals for in vivo CCK-B receptor imaging. Labeling of CCK8 with (111)In was achieved at the N-terminus of the peptide by adding, in solid phase, a glutamate coupled diethylenetriaminepentaacetic acid (DTPA) moiety through a glycine linker, yielding DTPA-Glu-G-CCK8. For labeling with (99m)Tc, the CCK8 peptide was modified at its N-terminus by introducing, in the following order--cysteine, glycine, and a diphenylphosphinopropionyl moiety--giving a 10-residue peptide derivative, Phos-GC-CCK8. A cell culture model was developed for the purpose of evaluating the binding properties of these two ligands. The human epidermoid carcinoma cell line, A431, was transfected with a plasmid containing the full coding sequence of the human CCK-BR under a strong viral promoter, obtaining a number of receptors in the range of 2-5 x 10(6) per cell. Control cells were transfected with vector alone. An animal tumor model utilizing these two cell lines was developed to evaluate the specificity of interaction with the CCK-BR and biodistribution properties of the compounds. CCK-BR positive and control cells were subcutaneously injected in opposite flanks of CD1 female nude mice in order to obtain xenografts differing only in their ability to express CCK-B receptors. High performance liquid chromatography (HPLC) and other chromatographic methods were utilized to assess stability of the radiolabeled compounds after injection. Both (111)In-DTPA-Glu-G-CCK8 and (99m)Tc-Phos-GC-CCK8 showed similar binding affinities for cultured CCK-BR expressing cells, with dissociation constants in the range of 20-40 nM. With the two xenograft approach, we were able to demonstrate specific interaction with the receptor of both CCK analogs in our animal model. The data obtained shows rapid specific localization of both compounds on the CCK-BR overexpressing xenografts. Both tracers show rapid plasma clearance of unbound peptide. Clearance of (111)In-DTPA-Glu-G-CCK8 appears to be preferentially through the kidneys, whereas (99m)Tc-Phos-GC-CCK8 clearance occurs both through kidneys and the hepatobiliary system. Both our labeling approaches appear adequate for clinical use of peptide based radiopharmaceuticals, although (99m)Tc-Phos-GC-CCK8 shows elevated accumulation in the gastrointestinal tract, which causes high background activity.

Animals↗
PubMed2001

Scintimammography with 99mTc-MIBI versus dynamic MRI for non-invasive characterization of breast masses.

Although mammography remains the technique of choice for the early detection of breast cancer, several imaging techniques, including scintimammography and magnetic resonance imaging (MRI), have recently been proposed as adjuncts for this purpose and included in many diagnostic protocols. This study was undertaken to assess the clinical accuracy of scintimammography with technetium-99m methoxyisobutylisonitrile (MIBI) and contrast-enhanced MRI in the detection of primary breast carcinoma in patients with equivocal mammographic findings. Forty-nine patients with a suspicious breast mass detected either by physical examination or by mammography and ultrasound (US) were studied. All patients underwent scintimammography and dynamic contrast-enhanced MRI 1 week apart. The results of the two techniques were compared and correlated to the final diagnoses. Two independent readers reported the scans using a four-point confidence scale. The areas under the receiver operator characteristic (ROC) curves were obtained. Scintimammography showed an accuracy for tumour detection of 84%, with a sensitivity of 80% and a specificity of 88%. MRI showed an accuracy of 86%, with a sensitivity and specificity of 96% and 75%, respectively. Comparison of the two areas under the ROC curves showed no significant differences between MRI, 0.91+/-0.05 (mean+/-SD), and scintimammography, 0.88+/-0.05 (P=0.9). It is concluded that dynamic MRI and scintimammography possess comparable accuracy in the diagnosis of primary breast carcinoma in patients with equivocal mammographic or US findings.

Biopsy↗
PubMed2001

Bone marrow uptake of 99mTc-MIBI in patients with multiple myeloma.

In a previous study, we showed the ability of technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) scan to identify active disease in patients with multiple myeloma (Eur J Nucl Med 1998; 25: 714-720). In particular, a semiquantitative score of the extension and intensity of bone marrow uptake was derived and correlated with both the clinical status of the disease and plasma cell bone marrow infiltration. In order to estimate quantitatively 99mTc-MIBI bone marrow uptake and to verify the intracellular localization of the tracer, bone marrow samples obtained from 24 multiple myeloma patients, three patients with monoclonal gammopathy of undetermined significance (MGUS) and two healthy donors were studied for in vitro uptake. After centrifugation over Ficoll-Hypaque gradient, cell suspensions were incubated with 99mTc-MIBI and the uptake was expressed as the percentage of radioactivity specifically retained within the cells. The cellular localization of the tracer was assessed by micro-autoradiography. Twenty-two out of 27 patients underwent 99mTc-MIBI scan within a week of bone marrow sampling. Whole-body images were obtained 10 min after intravenous injection of 555 MBq of the tracer; the extension and intensity of 99mTc-MIBI uptake were graded using the semiquantitative score. A statistically significant correlation was found between in vitro uptake of 99mTc-MIBI and both plasma cell infiltration (Pearson's coefficient of correlation r=0.69, P<0.0001) and in vivo score (Spearman rank correlation coefficient r=0.60, P<0.01). No specific tracer uptake was found in bone marrow samples obtained from the two healthy donors. Micro-autoradiography showed localization of 99mTc-MIBI inside the plasma cells infiltrating the bone marrow. Therefore, our findings show that the degree of tracer uptake both in vitro and in vivo is related to the percentage of infiltrating plasma cells which accumulate the tracer in their inner compartments.

Aged↗
PubMed2001

Predictive value of technetium-99m sestamibi in patients with multiple myeloma and potential role in the follow-up.

Technetium-99m 2-methoxyisobutylisonitrile (99mTc-MIBI or setamibi) has recently been proposed for use in the evaluation of multiple myeloma (MM). The aims of this study were to investigate its potential predictive value in patients with MM and its possible role in the follow-up. Thirty patients with MM who had undergone two 99mTc-MIBI scintigraphic studies at least 2 months apart constituted the study group; 22 of them received chemotherapy in the interval between the two scans. The scans were classified as showing pattern N when only physiological uptake was present, pattern D when diffuse bone marrow uptake was observed, pattern F when areas of focal uptake of the tracer were evident, and pattern F + D when both D and F patterns were observed. Comparative 99mTc-MIBI scintigraphy was considered indicative of disease progression when there was a worsening of the pattern (i.e. from N to D, or from N or D to F or to F + D) or an increase in the pattern D semiquantitative score. It was considered indicative of disease improvement when the opposite trend was observed; otherwise, it was considered to document a stable condition. A significant association was observed between the baseline scintigraphic pattern and clinical status at follow-up in the group of patients evaluated after chemotherapy (chi 2 = 16.7, P < 0.05). A negative baseline 99mTc-MIBI scintigram showed a high predictive accuracy (100%) for remission, while the presence of pattern F or F + D was often associated with a less favourable outcome. A multivariate analysis showed that 99mTc-MIBI uptake pattern has an added value in relation to known prognostic variables such as C-reactive protein. 99mTc-MIBI scintigraphy patterns at follow-up were significantly associated with the clinical status evaluated after chemotherapy (chi 2 = 32.6, P < 0.0001). Considering pattern N as indicating remission, pattern D stable condition, and pattern F or F + D progressive disease, a high concordance between scintigraphic findings and clinical status was found in the 22 patients undergoing chemotherapy (91%). Variation in 99mTc-MIBI findings comparing baseline and follow-up evaluations was significantly associated with clinical status both in patients undergoing chemotherapy (chi 2 = 26.5, P < 0.0005) and in those not undergoing chemotherapy (chi 2 = 8.0, P < 0.005). In conclusion, the results of this study suggest a prognostic value of 99mTc-MIBI scintigraphy in patients with MM and a potential role during the follow-up.

Aged↗
PubMed2000

Coordinate up-regulation of Sp1 DNA-binding activity and urokinase receptor expression in breast carcinoma.

The regulatory mechanisms underlying the overexpression of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in highly invasive breast carcinomas remain poorly understood. In this study, we have simultaneously determined the level of uPAR and the activity of the transcription factor Sp1 in 14 breast carcinomas and 5 benign lesions. We found that uPAR levels and Sp1-binding activity are coordinately elevated in malignant tumors (r, 0.94; P < 0.001). On the contrary, undetectable or only barely detectable levels of uPAR and Sp1 activity were found in benign breast lesions. Finally, the engagement of uPAR by catalytically inactive uPA in the MDA-MB-231 breast carcinoma cell line results in a rapid up-regulation of Sp1-binding activity followed by an increase of uPAR protein. These results, taken together, suggest the existence of a uPA-dependent positive regulatory loop that may progressively enhance malignant breast cell invasiveness.

Adult↗
PubMed2000

Scintigraphic detection of multidrug resistance in cancer.

One of the most extensively studied mechanisms of drug resistance involves the drug efflux pump P-glycoprotein (Pgp). The availability of radiolabeled substrates of Pgp such as 99mTc-MIBI and analogous 99mTc-labeled agents allows the clinical assessment of Pgp function in cancer patients. The consistency of the results from different institutions and trials strongly support the clinical application of this imaging technique for individual tailoring of chemotherapeutic regimens and for designing clinical trials with Pgp modulators.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Urokinase receptor interacts with alpha(v)beta5 vitronectin receptor, promoting urokinase-dependent cell migration in breast cancer.

Perturbation of adhesive interactions at cell-substratum and cell-cell contact sites is a critical event in the multistep process of cancer invasion. Recent studies indicate that the urokinase receptor (uPAR) is associated in large molecular complexes with other molecules, such as integrins. To test the possibility that uPAR may physically and functionally interact with vitronectin (Vn) receptors, we determined the expression level of uPAR, alpha(v)beta3, and alpha(v)beta5 Vn receptors in 10 human breast carcinomas. Here, we show the ability of uPAR to physically associate with alpha(v)beta5 in the breast carcinomas examined. The functional effects of this interaction were studied using HT1080 human fibrosarcoma and MCF-7 human breast carcinoma cell lines, both exhibiting a urokinase-dependent physical association between uPAR and alpha(v)beta5. Both cell lines respond to urokinase or to its noncatalytic amino-terminal fragment by exhibiting remarkable cytoskeletal rearrangements that are mediated by alpha(v)beta5 and require protein kinase C activity. On the contrary, binding of Vn to alpha(v)beta5 results in the protein kinase C-independent formation of F-actin containing microspike-type structures. Furthermore, alpha(v)beta5 is required for urokinase-directed, receptor-dependent MCF-7 and HT1080 cell migration. These data show that uPAR association with alpha(v)beta5 leads to a functional interaction of these receptors and suggest that uPAR directs cytoskeletal rearrangements and cell migration by altering alpha(v)beta5 signaling specificity.

Adult↗
PubMed1999

Mucosal expression of carcinoembryonic antigen and carbohydrate antigen 19-9 in patients with gastritis and gastric cancer.

Sixty-eight patients (45 males, 23 females) were studied in order to assess the usefulness of mucosal tissue concentrations of both carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in detecting patients at high risk for gastric cancer. CEA and CA19-9 were assayed on cytosol obtained from multiple endoscopic biopsies of 41 patients with chronic superficial gastritis, 18 with chronic atrophic gastritis, and 9 with gastric cancer. Mucosal tissue concentrations of both CEA and CA19-9 increased from chronic superficial gastritis to chronic atrophic gastritis and to gastric cancer (p = 0.005 and p = 0.002, respectively). Mucosal CEA levels in patients with intestinal metaplasia (IM) were significantly higher than in nonmetaplastic mucosa (p = 0.04). Epithelial dysplasia was associated with higher, though not significant, tissue concentrations of both CEA and CA19-9 when compared with IM. Finally, a correlation between serum levels and tissue concentrations was observed only for CA19-9 (Pearson's correlation coefficient = 0.7). In conclusion, these data indicate that gastric mucosa of patients with chronic atrophic gastritis and intestinal metaplasia express high levels of both CA19-9 and CEA.

Adult↗
PubMed1999

Detection of focal myeloma lesions by technetium-99m-sestaMIBI scintigraphy.

BACKGROUND AND OBJECTIVE: The tracer tachnetium-99m-2-methoxy-isobutyl-isonitrile (Tc99m-sestaMIBI) has recently been shown to concentrate in some neoplastic tissues, including myeloma. We investigated the diagnostic capacity and limits of this procedure in tracing focal myeloma lesions, and compared them with those of conventional radiological procedures (Xr). DESIGN AND METHODS: We studied 55 patients suffering from multiple myeloma (MM) or solitary plasmacytoma in different stages and clinical conditions, or from monoclonal gammopathy of undefined significance (MGUS), by whole body scans obtained 10 minutes after injection of 555 MBq of Tc99m-sestaMIBI. Scans were defined as normal (physiological uptake only), diffuse (presence of bone marrow uptake), or focal (localized areas of uptake), and were compared to conventional skeletal Xr. RESULTS: Thirty patients showed no focal areas of Tc99m-sestaMIBI uptake; this group consisted of 5 patients with MGUS, 6 with MM in stage IA and 2 in stage IIA, 11 patients studied after effective chemotherapy and 6 in early relapse. Twenty-five patients showed one or more spots of focal uptake: all of them had active disease (untreated, resistant or relapsing MM). In the setting of tracing focal lesions, Tc99m-sestaMIBI scans were concordant with the radiological examination in 38 patients and discordant in 17. Among the latter, in 4 cases Tc99m-sestaMIBI revealed focal lesions not detected by Xr, and in 13 cases lytic areas detected by Xr did not show Tc99m-sestaMIBI uptake. INTERPRETATION AND CONCLUSIONS: In untreated patients, the number of lesions revealed by Tc99m-sestaMIBI was comparable to that shown by Xr, while in pretreated patients Tc99m-sestaMIBI traced a number of lesions lower than that detected by Xr. The reason for this discrepancy is that Tc99m-sestaMIBI traces only active lesions. Tc99m-sestaMIBI limitations in identifying focal lesions may derive from the dimension of the smallest traceable lesion (about one centimeter), and from the possibility that focal plasma cell localizations in collapsed bone may not be visualized due to inadequate vascularization. Tc99m-sestaMIBI scintigraphy is an interesting tool for diagnosing, staging and following up focal myeloma lesions, in the bone as well as in soft tissues. It is more specific than conventional Xr in identifying sites of active disease.

Adult↗
PubMed1999

Clinical imaging of multidrug resistance in cancer.

The most well-characterized mechanism of multidrug resistance (MDR) involves P-glycoprotein (Pgp), a transmembrane protein acting as an ATP-dependent drug efflux pump. The recognition of 99mTc-Sestamibi and other lipophilic cations as transport substrates for Pgp provided the necessary tool for the clinical assessment of Pgp function in patients with cancer. Many clinical studies from different institutions and trials including a variety of malignancies indicate that both tumor uptake and clearance of 99mTc-Sestamibi are correlated with Pgp expression and may be used for the phenotypic assessment of multidrug resistance. Although both parameters may predict tumor response to chemotherapy, the extraction of efflux rate constants appeared to provide a more direct index of Pgp function as compared to tracer uptake ratio allowing to trace a continuous spectrum of drug transport activity. Preliminary studies reported the use of MDR imaging agents to monitor the modulating ability of revertant compounds. Although the results support the feasibility of this approach, the alteration of tracer pharmacokinetics induced by the modulators certainly constitutes a challenge in the development of a simple functional test suitable in clinical practice. The extension of the acquired imaging methodology to tumors with redundant intrinsic resistant mechanisms such as lung cancer requires further investigations on the relative contribution and clinical relevance of each mechanism. Due to the multifactorial nature of the phenomenon, the development of new tracers with substrate specificity for other known drug transporters would hopefully help to dissect the complex array of cellular mechanisms contributing to treatment failure.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1998

Different patterns of technetium-99m sestamibi uptake in multiple myeloma.

Technetium-99m 2-methoxyisobutylisonitrile (99mTc-MIBI) has been proposed as a potential tracer in patients with multiple myeloma (MM). The aims of this study were to evaluate the incidence of various patterns of diffuse 99mTc-MIBI uptake in patients with MM, to assess their relationship with clinical status and stage of disease, and to try to clarify the meaning of the diffuse bone marrow uptake of 99mTc-MIBI. Thirty-nine consecutive patients with MM were studied. Twenty-nine of these patients had active disease (13 in stage I, ten in stage II, and six in stage III) and ten were in remission after chemotherapy. Anterior and posterior whole-body scans were obtained 10 min after i.v. injection of 555 MBq of 99mTc-MIBI. The scans were classified as showing: pattern N, when only physiological uptake was present; pattern D, when diffuse bone marrow uptake was observed; pattern F, when areas of focal uptake of the radiotracer were evident; or pattern D+F, when both D and F patterns were observed. Diffuse bone marrow uptake was scored according to extension and intensity. Seven of the 39 patients (18%) showed pattern N, 18 (46%) pattern D, 2 (5%) pattern F, and 12 (31%) pattern D+F. Of the 32 patients with a positive 99mTc-MIBI scan (i.e. showing pattern D, F or D+F), 29 (91%) had active disease. Only three patients in remission showed pattern D, but with a very low bone marrow uptake score. Both extension and intensity of diffuse bone marrow uptake correlated with the amount of the monoclonal component and the percentage of bone marrow plasma cells. The distribution of the 99mTc-MIBI uptake patterns differed among patients in different stages of disease. Using as criteria for advanced stage the presence of either focal uptake (pattern F or D+F) or pattern D with a high score, high (90%) diagnostic accuracy was obtained. In conclusion, the patterns of 99mTc-MIBI uptake in patients with MM are related to both the clinical status and the stage of disease. The presence of focal uptake or of intense diffuse bone marrow uptake suggests that the patient has active and advanced stage disease, while a negative scan in a patient with MM clearly indicates remission.

Antibodies, Monoclonal↗
PubMed1998

Dynamic imaging: scintimammography.

Although mammography remains the technique of choice for the early detection of breast cancer, new emerging breast imaging techniques such as ultrasound, magnetic resonance and radionuclide scanning have been investigated and included in many diagnostic protocols. This overview discusses the current problems related to radionuclide breast imaging trying to define its role in the management of women with suspicious breast lesions at mammography. A number of tumor-imaging agents have been recently used for the differential diagnosis of malignant and benign lesions in radiographically dense breasts and breasts with architectural distortions from prior biopsy or surgery or following radiation therapy. 99mTc-MIBI is the most used tracer which has become the paradigm of this new class of compounds suitable for breast imaging. The current sensitivity and specificity rates for breast scintigraphy with 99mTc-MIBI depend on a number of factors including lesion size and site. Sensitivity and specificity rates and positive and negative predictive values of 92, 89, 81 and 96%, respectively, have been reported in a large series of patients with palpable breast lesions, which figures have been confirmed in many other series. On the contrary, lower sensitivity has been reported for nonpalpable breast abnormalities or for lesions smaller than 1 cm. This observation, confirmed by many authors, implies that a new nonpalpable lesion that is suspicious for malignancy at mammography needs a histologic diagnosis. We also report the results of our recent studies on functional imaging with 99mTc-MIBI of the multidrug resistance phenotype in breast cancer patients. These studies followed an observation that this tracer is a suitable transport substrate for the P-glycoprotein (P-gp) which is commonly associated with the development of a multidrug resistance phenotype. We examined 30 patients with histologically confirmed breast carcinoma who had received no previous chemotherapy or preoperative local irradiation. We found a positive and significant correlation between the efflux rates of 99mTc-MIBI determined by in vivo kinetic analysis and the P-gp levels measured in vitro by quantitative autoradiography in the same tumors (r = 0.62; p < 0.001). More recently, we tested whether tumor clearance of 99mTc-MIBI can predict the response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. Thirty-nine patients with stage III disease underwent 99mTc-MIBI scanning before neoadjuvant chemotherapy and the time to half-clearance of the tracer was calculated. The patients then received epirubicin and underwent mastectomy after completing chemotherapy. This study showed that a rapid tumor clearance of 99mTc-MIBI (< or = 204 min) can predict the lack of tumor response to neoadjuvant chemotherapy with drugs affected by multidrug resistance phenotype in advanced breast carcinoma patients. However, slower tracer clearance (> or = 204 min) did not guarantee an objective tumor response to chemotherapy in all patients, in agreement with the existence of several P-gp-independent mechanisms of drug resistance. We conclude that the preliminary study of this phenotype would allow to predict the response to (neo)adjuvant chemotherapy and select the appropriate treatment regimen for each patient. Finally, radionuclide breast scanning may be helpful in the differential diagnosis of malignant and benign breast lesions as a guide to subsequent chemotherapy.

Antineoplastic Agents↗