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E Bombardieri

Publications and source records attributed to E Bombardieri.

At least 55 records · Page 3Linked to original sources

The objective measurement of remission and progression in metastatic breast cancer by use of serum tumour markers. European Group for Serum Tumour Markers in Breast Cancer.

An established biochemical index for monitoring therapy in patients with metastatic breast cancer was tested prospectively in a multicentre study. The index uses two serum tumour markers--carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3) along with erythrocyte sedimentation rate (ESR). 67 patients treated by either endocrine or chemotherapy had CA15-3, CEA and ESR measured at diagnosis of metastases and sequentially during therapy. Two markers, CA15-3 and CEA, were measured on a further 16 patients giving a total of 83 patients who were assessable for CA15-3 and CEA. Of the patients with CA15-3, CEA and ESR measured at diagnosis of metastases 84% (56/67) had elevation of 1 or more markers. During therapy the number with elevated marker(s) rose to 96% (64/67). Changes in the markers were in line with and often pre-dated therapeutic outcome as assessed by the International Union Against Cancer (UICC) criteria both for remission and progression. Patients without elevation of markers on diagnosis subsequently showed a rise in the marker(s) at or before documented disease progression by UICC. The 3 women in whom markers were at no time significantly elevated remain in remission. The results using CA15-3 and CEA were similar but 12% less patients were assessable. CA15-3 and CEA (with and without ESR) provide an objective method to guide therapy in patients with metastatic breast cancer.

Antigens, Tumor-Associated, Carbohydrate↗

Current applications and perspectives of diagnostic nuclear medicine in oncology. Task Group of Oncology.

The characteristic of nuclear medicine is that it gives images of organs, structures and physiological or pathological processes, detecting the distribution of several radio-pharmaceuticals according to their uptake and metabolism. Its imaging can provide morphological information while at the same time containing data on cellular activity and functions. Such molecular imaging fulfils the modern orientations of oncology, where there is a need to define the presence of a malignancy in the earliest and most effective way, to characterise the neoplasm in terms of biological characteristics (e. g., proliferation, aggressiveness, differentiation, receptor status) and to obtain fundamental issues in patient management such as evaluation of disease extent, monitoring of therapies and study of treatment-induced side effects. The aim of this position paper is to discuss the main indications of nuclear medicine in diagnostic oncology reporting the most recent developments in nuclear medicine, and an extensive list of the major indications for nuclear medicine procedures. The techniques have been labelled as when considered essential in the diagnostic process, when they can give useful additional or information in combination with other instrumental diagnostic approaches, and alternative when they may be performed instead of other tests. These indications were derived by a general consensus within the Task Group of Oncology of the World Federation of Nuclear Medicine and Biology, and it should be stressed that only the current role of nuclear medicine was considered. The Task Group does not claim to have covered the entire range of nuclear medicine indications; in fact it was agreed to include only the most widely used techniques. The highly specific or very exceptionally used applications, or those still in development or under evaluation in clinical trials were not taken into consideration. The conclusion is that the current relationship between nuclear medicine and oncology can be defined not only as satisfactory but also as extremely promising, as nuclear medicine has the potential to compete with the most advanced radiological techniques of imaging, perhaps not so much in terms of sensitivity but more so in terms of specificity and biological characterisation. Several novel diagnostic procedures are able to solve clinical problems for which traditional radiology has shown clear limitations. Nuclear medicine remains today a dynamic medical specialty because it includes a combination of advances in basic science research, technology, cell biology and medical practice and it cannot be excluded that the new lines of research both towards new radiopharmaceuticals and advanced instrumentation will offer in the future new stimulating opportunities.

Forecasting↗

Multicenter trial of the quantitative BTA TRAK assay in the detection of bladder cancer.

BACKGROUND: Human complement factor H-related protein (hCFHrp) is produced by several bladder cancer cell lines and may be useful as a cancer marker. The aim of this study was to compare urinary hCFHrp and cytology for the detection of bladder cancer found by cystoscopy in patients with suggestive signs, symptoms, or preliminary test results. METHODS: The BTA TRAK assay, a quantitative enzyme immunoassay for the bladder tumor-associated antigen in urine, was compared with exfoliative cytology in 220 patients (155 men, 65 women; mean age, 64.2 years) presenting with signs, symptoms, or preliminary diagnostic results suggestive of this disease. Cystoscopy was the standard of detection. RESULTS: In the 100 patients found to have bladder cancer, the overall sensitivities of the BTA TRAK assay (at a previously determined decision threshold of 14 kilounits/L) and cytology were 66% (66 of 100) and 33% (33 of 100), respectively (P <0.001). The BTA TRAK assay proved to be statistically more sensitive than cytology for tumor grades I and II and for stage Ta and T1 tumors. In contrast, the overall specificity of the BTA TRAK assay in the 120 patients without cystoscopically confirmed bladder cancer was 69% (83 of 120) and that of cytology was 99% (119 of 120; P <0.001). The specificity of the BTA TRAK assay was higher in patients without benign or malignant genitourinary disease other than bladder cancer (76%; n = 89) than in patients with these conditions. When the BTA TRAK assay and cytology were used together such that a positive result in either test was scored as positive and the results compared with those of the BTA TRAK assay alone, increases in overall sensitivity and equivalent specificity were observed. CONCLUSION: Because of its relatively high sensitivity, the BTA TRAK assay could complement cytology as an adjunct to cystoscopy in the diagnosis and follow-up of most patients with bladder cancer.

Adult↗

Imaging of neuroendocrine gastro-entero-pancreatic tumours using radiolabelled somatostatin analogues.

Neuroendocrine tumours of the gastro-entero-pancreatic tract are an uncommon clinical entity and are believed to arise from the endocrine cells of the gastrointestinal tract. Somatostatin receptor imaging is a diagnostic tool which allows visualization of somatostatin receptor bearing tumours. This scintigraphic procedure is performed with indium-111 labelled octreotide, a somatostatin analogue, chelated with diethylene triamine penta-acetic acid. Radionuclide imaging consists in detecting the biodistribution of somatostatin receptors, normally expressed on the cell surface of neuroendocrine gastro-entero-pancreatic tumours. To date, five types of this receptor have been cloned: indium-111-labelled-pentetreotide can visualize tumours expressing type 2 and 5 receptors. The results of our study, which involved 81 neuroendocrine gastro-entero-pancreatic tumour patients, confirm the superior sensitivity of somatostatin receptor imaging (61%) for primary tumour evaluation with respect to conventional imaging modalities such as computed tomography (40%) or ultrasound (28%). Scintigraphic findings in metastatic liver disease proved to have a sensitivity of 89% for somatostatin receptor imaging, versus 81% and 88% for computed tomography and ultrasound, respectively. In 23% of patients, lesions were found with somatostatin receptor imaging which had been missed using the other diagnostic modalities; in 26% of the patients the therapeutic approach was modified after somatostatin receptor imaging.

Adolescent↗

Effect of steroid receptors, pS2 and cathepsin D on the outcome of elderly breast cancer patients: an exploratory investigation.

In 83 elderly breast cancer patients, oestrogen and progesterone receptors (ER, PgR), pS2 and cathepsin D (CathD) were evaluated for their possible prognostic role on disease-free survival (DFS). The biomarkers were determined on the same cytosol by using immunoradiometric assays, and the variables were considered on a continuous scale. Univariate analysis indicated a linear relationship between logarithmic hazard ratio (log(HR)) and the log(ER) and log(PgR) concentration, but a non-linear relationship between log(HR) and CathD. As regards pS2, there was no evidence of a relationship with log(HR). In multivariate analysis, log(ER) content did not have a significant prognostic role, whereas log(PgR) retained a significant prognostic role. As regards the predictive ability, log(PgR) was the best discriminator of outcome followed by CathD, whereas the contribution of log(ER) was negligible. In multivariate analysis, 2 models were considered: one with log(ER), pS2, CathD and the interaction between pS2 and CathD, and another with log(PgR), pS2, CathD and the interaction between pS2 and CathD. In the first model, log(ER) content did not have a significant prognostic role, whereas in the second model log(PgR) retained a significant prognostic role. Our findings indicate that the quantitative determination of pS2 and CathD, in addition to steroid receptors, on the same cytosolic fraction could be a complementary tool to describe all breast cancer patients rather than just the elderly and that the use of a continuous scale, instead of a simple dichotomous "status", may improve the biological information supplied by the variables.

Aged↗

A randomized, controlled clinical trial to evaluate the effects of zinc sulfate on cancer patients with taste alterations caused by head and neck irradiation.

BACKGROUND: In uncontrolled clinical trials, the administration of oral zinc sulfate has been reported both to prevent and correct taste abnormalities in cancer patients receiving external radiotherapy (ERT) to the head and neck region. METHODS: Eighteen patients were randomized to receive either zinc sulfate tablets (a dose of 45 mg) or placebo tablets three times a day at the onset of subjective perception of taste alterations during the course of ERT and up to 1 month after ERT termination. Taste acuity was determined by measuring detection and recognition thresholds for four taste qualities. Intolerance of zinc sulfate or placebo administration was investigated, and the oral cavity was examined. All the evaluations were studied prior to, at weekly intervals during, and 1 month after ERT administration. RESULTS: Taste acuity for one or more taste qualities was already impaired before ERT. During ERT treatment, taste alterations were experienced at least once for a minimum of 3 of the 8 measured thresholds by 100% of the patients, and 33.3% of the patients became aware of some alteration within the first week of treatment. The patients treated with placebo experienced a greater worsening of taste acuity during ERT treatment compared with those treated with zinc sulfate. One month after ERT was terminated, the patients receiving zinc sulfate had a quicker recovery of taste acuity than those receiving placebo. Statistically significant differences between the two groups emerged for urea detection and sodium chloride recognition thresholds during ERT treatment and for sodium chloride, saccharose, and hydrogen chloride recognition thresholds after the termination of ERT treatment. CONCLUSIONS: This pharmacologic therapy is effective and well tolerated; it could become a routine in clinical practice to improve the supportive care of patients with taste alterations resulting from head and neck cancer.

Administration, Oral↗

Radionuclide imaging of neuroendocrine tumours: biological basis and diagnostic results.

Neuroendocrine tumours have been defined as APUD-omas in the past by authors who identified common metabolic characteristics (amine precursor uptake and decarboxylation) in a group of tumours thought to originate from cells of the neural crest and to be able to produce biogenic amines. The identification of neuroendocrine tumours with APUD-omas was not confirmed by subsequent investigators. At present it is known that a group of neuroendocrine tumours derive from pluripotent stem cells or from differentiated neuroendocrine cells, and that they have a particular pattern of histology due to the presence of some secretory products and particular cytoplasmic proteins. Many radiopharmaceuticals have been successfully used in nuclear medicine to visualise neuroendocrine tumours; most of them are based on specific uptake mechanisms, but some are non-specific probes. This review is focussed on the clinical application of radiolabelled metaiodobenzylguanidine, indium-111 pentetreotide, radiolabelled vasointestinal peptide, radiolabelled monoclonal antibodies and positron-emitting tracers. While many different types of neuroendocrine tumours are identified today, only the most common histotypes and those tumours of major relevance for nuclear medicine are considered in this review (anterior pituitary tumours and neuroblastoma are excluded). New knowledge in molecular biology, relevant biological and histological patterns, and the physiological and clinical behaviour are described for neuroendocrine tumours of the lung, tumours of the gastroenteropancreatic tract, medullary thyroid carcinoma, tumours of sympatho-adrenal lineage, and multiple endocrine neoplasia. The nuclear medicine results in diagnostic imaging are presented, and the major comparative studies with different tracers are reported. The study of further possible diagnostic approaches addressing the biological characteristics of these tumours could open the way to various new therapeutic options.

Humans↗

Comparison of somatostatin receptor imaging, computed tomography and ultrasound in the clinical management of neuroendocrine gastro-entero-pancreatic tumours.

Neuroendocrine tumours displaying somatostatin receptors have been successfully visualised with somatostatin receptor imaging (SRI). However, there may be differences in sensitivity depending on the site of the primary tumour and/or its metastases. We studied 131 patients affected by neuroendocrine tumours of the gastro-entero-pancreatic (GEP) tract. A pathological diagnosis was obtained in 116 patients, while in 15 the diagnosis was based on instrumental results and follow-up. Fifty-one patients were examined for staging purposes, 80 were in follow-up. Images were acquired 24 and 48 h after the injection of 150-220 MBq of indium-111 pentetreotide. Whole-body and SPET images were obtained in all patients. Patients were also studied with computed tomography (CT), ultrasound (US), and other procedures. Tumours were classified according to their site of origin: pancreas n = 39, ileum n = 32, stomach n = 16, appendix n = 9, duodenum n = 5, jejunum n = 5, rectum n = 3, biliary tract n = 2, colon n = 2, caecum n = 1, liver metastases from unknown primary = 15, widespread metastases from unknown primary = 2. Sensitivity for primary tumour localisation was as follows: SRI = 62%; CT = 43%; US = 36%; other procedures = 45%. Sensitivity for liver metastases: SRI = 90%; CT = 78%; US = 88%; other procedures = 71%. Sensitivity for the detection of extrahepatic soft tissue lesions was: SRI = 90%; CT = 66%; US = 47%; other procedures = 61%. Sensitivity for the detection of the primary tumour in patients with metastases from unknown primary sites: SRI 4/17; CT 0/13; US 0/12; other procedures 1/10. In 28% of the patients SRI revealed previously unknown lesions, and in 21% it determined a modification of the scheduled therapy. Our study confirms the important role of SRI in the management of GEP tumours. However, we feel that a critical investigation should address its role in locating primary tumours, in particular in patients with metastases from unknown primary sites.

Adolescent↗

Association between [18F]fluorodeoxyglucose uptake and postoperative histopathology, hormone receptor status, thymidine labelling index and p53 in primary breast cancer: a preliminary observation.

To investigate the possible role of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) in the prognostic evaluation of primary breast cancer, we studied 86 patients with T1-3 (TNM classification) breast tumours before surgery and compared the tumour FDG uptake, calculated as a standardized uptake value (SUV), with postoperative histopathological findings, steroid hormone receptor status of the tumour, thymidine labelling index (LI) and tissular expression of p53. SUV was significantly higher in infiltrating ductal carcinomas (n = 68; median SUV = 5.6) than in lobular ones (n = 18; median SUV = 3.8), and in grade 3 carcinomas (n = 26; median SUV = 6.2) than in grade 1-2 ones (n = 60; median SUV = 4.9). Moreover, SUV was significantly higher in carcinomas with high levels of p53 (n = 12; median SUV = 9.5) than in those with low levels (n = 48; median SUV = 4.25). By contrast, there was no significant correlation between SUV and the steroid hormone receptor status or LI of tumours. Our data demonstrate that FDG uptake, expressed as SUV, is associated with certain prognostic factors in breast cancer, such as histopathological grading and p53 expression, which can be assessed only by means of postoperative in vitro examinations. Hence, the information provided by FDG-PET is to some extent related to relevant information on tumour biology. The clinical value of these data will have to be confirmed by analysis of the independence of SUV from other prognostic factors by means of a multivariate analysis performed on a larger series of patients with adequate follow-up. If SUV is confirmed as an independent variable, FDG-PET could assume an important role in the determination of appropriate therapeutic strategies for primary breast cancer.

Adult↗

P53 accumulation in primary breast cancer: a comparison between immunohistochemistry and a novel luminometric immunoassay.

The accumulation of p53 protein was evaluated by a novel luminometric immunoassay (LIA) in cytosol samples from a series of 245 primary breast cancers. The cytosolic p53 content was not related to nodal status or hormone receptor status, but it was significantly and directly associated with tumor size and cell proliferation. A matched comparison between immunohistochemistry (IHC) and LIA results of individual tumors showed a significant association, albeit with a correlation coefficient of only 0.41. The agreement of results from the two assays was higher in node-positive, estrogen-receptor-negative and rapidly proliferating tumors than in the complementary subgroups. Overall, there was a significant trend in favor of an increase in p53 levels as determined by LIA with the increase in p53-positive cells shown by IHC. However, taking IHC detection as a reference, the sensitivity of the LIA was better for negative (86%) than for positive (61%) values. Based on these findings, a comparative assessment of the clinical relevance of LIA versus IHC results has to be recommended.

Antibodies, Monoclonal↗

Neuron-specific enolase evaluation in patients with neuroblastoma.

Neuron-specific enolase (NSE) may be of interest for the prognostic evaluation and follow-up surveillance in patients with neuroblastoma. We evaluated NSE levels in 80 patients with neuroblastoma. The marker correlated with stage (in stage 1 patients, the median NSE level was 9.9 ng/ml, in stage 2, 45.1 ng/ml, in stage 3, 49 ng/ml, in stage 4, 93.9 ng/ml, in stage 4S, 53.4 ng/ml) and with survival. In patients with a favorable or a poor outcome, the difference in basal NSE serum levels was statistically significant (p = 0.0001). Serial measurements revealed that there was a good correlation between NSE levels and disease course. We concluded that NSE is a good marker for neuroblastoma and its quantitative determination in serum is valuable in the management of these patients to confirm the diagnosis, monitor the effect of treatment and detect recurrent disease.

Abdominal Neoplasms↗

[External exposure of hot cell operators in nuclear medicine].

PURPOSE: The coming into effect of decrees No. 626/94, 242/96 and 230/95 has once again brought out the problem of the radiation exposure of hot cell operators in nuclear medicine. MATERIAL AND METHODS: With regard to the activity of the Division of Nuclear Medicine of the Istituto Nazionale Tumori in Milan, a map has been produced of the radiation fields in the hot cell in- and outside the working station by measuring the rate of exposure and evaluating the radiation energy using film dosimeters in multifilter containers. The individual doses were measured with film dosimeters for the sternum, the back of the hand and the wrist, and with thermoluminescent dosimeters for the fingers and forehead. The thermoluminescent ring was worn with the detector towards the palm and towards the back of the hand in order to identify the side that was exposed most; the film dosimeter on the sternum was worn both underneath and above the lead apron to reveal a possible reduction in overall exposure due to attenuation of the lower-energy components. RESULTS: The diffuse radiation field in the hot cell during the usual working activity amounts to 1 microSv/h. Assessment of the energy of the radiation fields within the working station revealed a higher energy (90 to 140 keV) in the source storage area than in the area where the syringes are prepared, the latter being affected by diffuse radiation with components of approximately 35, 90 and 110 keV. The hand of the operator is unevenly exposed to the diffuse radiation field and the fingers are more exposed than the back of the hand and the wrist: when the thermoluminescent ring was worn with the detector towards the palm of the hand the measured values did not show a higher exposure than when it was worn with the detector towards the back of the hand. The equivalent of the overall dose measured underneath the lead apron did not show any relevant reduction of the exposure due to attenuation of the lower-energy component (approx. 35 keV). We report the dosimetric findings regarding the total and partial exposure of four different operators during their regular weekly shift, with the dosimeters for the sternum, ring finger and forehead being replaced daily. The average equivalent of the dose to the hand for the manipulation of 37 GBq of 99mTc, measured with a thermoluminescent ring on the proximal phalanx of the ring finger, ranged 3.9 mSv to 2.0 mSv. Except in one case, the sternum and forehead proved to be well protected by the shielding of the working station. DISCUSSION: The operator who stay in the hot cell for 5 hours/week accumulates, due to the presence of diffuse radiation, 5 microSv/week to the whole body; when his/her hands are inside the working station for 2.5 hours/week in the most unfavorable conditions as regards the presence of radioactive sources, they will be exposed to 1250 microSv/week, independently of dose preparation. The exposure of hot cell personnel is highly dependent on the ergonomics of the operator (build, height, arm spread, hand size, etc.) with respect to the position of the apertures and the inspection windows of the working station; as a consequence, the three dosimetric values (exposure of the sternum, the hands and the forehead) cannot be correlated. The fingers are the most exposed part of the hand, which confirms the appropriateness of our choice of the thermoluminescent ring to measure the partial exposure of the hands. Our results have been compared with those reported in the literature and with statistical data relative to three years of regular activity (1994-1996), during which the hot cell operators were monitored according to the same parameters; female operators proved to be more exposed than males, with average yearly equivalents of the total dose of 2764 microSv and 860 microSv, respectively, and average yearly equivalents of the partial dose to the hands of 32,288 microSv and 9460 microSv, respectively. The average total partial dose equivalent rati

Female↗

Prospective evaluation of fluorine-18-FDG PET in presurgical staging of the axilla in breast cancer.

METHODS: The presurgical, noninvasive staging of axillary nodes for metastases was prospectively investigated in 68 patients who were diagnosed with primary breast cancer using PET with 18F-fluorodeoxyglucose (FDG). Four patients had bilateral nodules; therefore, the total number of evaluable cases was 72. Visual analyses of attenuation-corrected PET images and standardized uptake values (SUVs) of FDG uptake in carcinomas were compared with histopathological surgical findings. The SUV distribution differences between carcinomas with and without axillary metastases were evaluated by means of statistical and receiver operating characteristics analyses. RESULTS: PET correctly classified 64 of the 72 cases; four false-positive and four false-negative PET results were found. The overall sensitivity, specificity and accuracy of PET for axillary metastases were 85%, 91% and 89%, respectively. With respect to the clinical axillary stage of the patients (TNM, or tumor-node-metastasis, classification), we obtained the following results: N0 patients, sensitivity = 70%, specificity = 92%, accuracy = 86%; N1a patients, sensitivity = 85.5%, specificity = 100%, accuracy = 95%; and N1b-2 patients, sensitivity = 100%, specificity = 67%, accuracy = 87%. The median SUV in carcinomas with axillary metastases (4.6) was significantly higher than that in carcinomas without metastases (2.9), but there was a great SUV overlap between the two groups (interquartile ranges = 2.7-7.2 and 1.9-4.5, respectively). Analysis of the receiver operating characteristics curve showed that a high sensitivity of SUV in predicting axillary metastases was associated with a very low specificity and vice versa. With the best SUV cutoff value of 2.9, the sensitivity and specificity were 74% and 56%, respectively. CONCLUSION: PET showed good overall diagnostic accuracy in the detection of axillary metastases (86%). The very high accuracy (95%) in N1a patients is of particular importance. False-negative PET findings, however, can be encountered. SUVs of breast carcinoma cannot predict the spread of the disease to the axilla, even if higher values are often associated with axillary metastases. Any decision on the use of PET in the presurgical staging of breast cancer should be incorporated into a more general debate on axillary management. In selected patients with a very low probability of axillary metastases (T1a), in whom axillary surgery can already be avoided according to data from follow-up studies, 18F-FDG PET could be proposed as a noninvasive imaging modality to improve the diagnosis of axillary relapses.

Axilla↗

Nuclear medicine approaches for detection of axillary lymph node metastases.

In breast cancer patients the detection of axillary lymph node involvement is a very critical issue, in view of the earlier diagnosis of the disease in recent years, and the increased frequency of very small tumors at first presentation. The size of cancer is related to the risk of axillary metastases, and this may affect the prognosis and the therapeutic strategies. Axillary lymph node involvement is generally recognized as an index of distant microdiffusion, and as it affects overall and disease-free survival, represents the basis for adoption of adjuvant chemotherapy. Routine axillary lymph node dissection (ALND) is expensive, and does not benefit about 70% of early breast cancer patients which are node negative (pN-). Today most of these patients have to sustain the potential morbidity and the economic costs of ALND. The clinical approach is known to be an unreliable diagnostic tool, and for the detection of axillary metastases, conventional X-ray techniques are also unable to solve the problem. By contrast, nuclear medicine procedures have revealed a very interesting diagnostic potential in recent years. This paper analyzes the numerous studies conducted in the field of lymph node visualization and the heterogeneity of the published experiences, taking into account the different approaches proposed in the literature: a) imaging with gamma-emitting tumor seeking agents; b) radioimmunoscintigraphy intravenous (i.v.) or by the interstitial route; c) lymphoscintigraphy with colloids and gamma probe sentinel biopsy; d) positron emission tomography (PET). Although it is very difficult to make a definitive statement about the clinical efficacy of all these methods, this paper reports the most important series of patients examined in the literature as well as the author's own experiences. This can serve as the basis for a better understanding of the potential of nuclear medicine procedures, and gives the reader the opportunity to weigh advantages and drawbacks of each method. At present, lymphoscintigraphy with gamma probe sentinel biopsy and FDG-PET are the nuclear medicine approaches with the best diagnostic performance. However, a correct comparison of the methods will not be possible, until their careful assessment in the same patients is performed. In addition, a final statement today should consider also the increasing need to carry out an economic analysis by evaluating the cost-effectiveness of the examinations.

Axilla↗

Gallium-67 scintigraphy evaluation of therapy in non-Hodgkin's lymphoma.

UNLABELLED: Patients with diffuse large cell lymphoma may achieve complete remission (CR) after chemotherapy, and the time to reach CR may be predictive of treatment outcome. Partial remission, or recurrence from CR, is associated with poor survival. Gallium-67 imaging has proven to be useful in evaluating lymphoma patients. In tumor models, this radiotracer is an indicator of tumor viability. Gallium-67 uptake is seen only in avid and viable lymphoma tissue, not in fibrotic or necrotic tissue. In this study, we prospectively assessed the ability of this radiotracer to define residual disease. In addition, we evaluated the possibility of predicting the clinical outcome in patients with diffuse cell lymphoma on the basis of scan positivity during chemotherapy. METHODS: Thirty-three consecutive patients with histologically proven diffuse large cell lymphoma were investigated with 67Ga scintigraphy 48-72 hr after injection of 185-259 MBq 67Ga-citrate for staging and during follow-up after four to six cycles of intensive chemotherapy. Patients were monitored for a mean of 56.0 mo (range 7-90 mo), and they were restaged using physical examination, CT and all necessary imaging modalities. RESULTS: Patients were divided into two groups according to the positivity or negativity of 67Ga scan after four to six cycles of chemotherapy. Of the 33 patients studied, 14 (42.4%) showed persistent abnormal uptake of 67Ga-citrate after four to six cycles of chemotherapy. In this group, 9 patients (64.2%) died of lymphoma at a mean of 24.3 mo from presentation with the diagnosis (range 7-71 mo). Four patients had no evidence of disease at an average of 71.7 mo after diagnosis, and 1 patient was considered to be in partial remission. In the second group of 19 67Ga-negative patients, after four to six cycles of chemotherapy, 4 died and 15 are alive and considered to be in CR. A statistical analysis of the association between 67Ga scan results after four to six cycles of chemotherapy and survival was performed using the log-rank test; there was a statistically significant association between scan results and survival (p=0.00125). CONCLUSION: We conclude that 67Ga scintigraphy is an excellent predictor of residual tumor viability in lymphoma patients and that persistent positivity of the scan predicts poor outcome and may justify a change in treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Comparison of three different methods for radiolabelling human activated T lymphocytes.

One approach in the treatment of ovarian cancer patients involves the infusion of autologous T lymphocytes coupled with a bispecific monoclonal antibody MOv18/anti-CD3 (biMAb OC/TR), which recognizes a 38-kDa glycoprotein expressed on ovarian carcinomas and the CD3 T cell receptor. However, little is known about the in vivo biodistribution of injected activated lymphocytes, information that could be obtained by scintigraphic imaging of radiolabelled T cells in order to visualize the migratory pattern. We compared the efficiency, stability and toxicity of technetium-99m hexamethylpropylene amine oxime (HMPAO), indium-111 oxine and fluorine-18 2-fluoro-2-deoxy-d-glucose (FDG) in radiolabelling activated lymphocytes targeted with biMAb OC/TR. The mean labelling efficiencies of 111In-oxine and 18F-FDG using 2.5x10(8) lymphocytes (68% and 64%, respectively) were more than twice that of 99mTc-HMPAO (31%). Retention of the radionuclide in the cell was highest in the case of 111In-oxine labelling (less than 25% of the initial cell-bound activity released after 240 min, as compared with 44% of the 99mTc label in the same period and 45% of 18F radionuclide released after 150 min). None of the three radiolabelling reagents induced any significant alteration in cell viability or immunophenotype. However, both 111In-oxine and 18F-FDG induced a loss of cytotoxic activity of lymphocytes against the ovarian carcinoma cell line IGROV1, and all three radiolabelling reagents caused a significant reduction in the proliferative ability of labelled lymphocytes compared to controls, with cell death occurring after 8-9 days. Radiolabelling with the more stable 111In-oxine reagent using a higher number of lymphocytes (1.4x10(9)) but the same total activity (around 55.5 MBq) resulted in improved labelled T cell viability and proliferative ability, although the mean labelling efficiency decreased (35.8%). Together the data suggest that 111In-oxine at low activity per cell is the most appropriate reagent for radiolabelling activated retargeted T lymphocytes useful for in vivo biodistribution studies.

Cell Death↗