Single-dose intraperitoneal radioimmunotherapy with the murine monoclonal antibody I-131 MOv18: clinical results in patients with minimal residual disease of ovarian cancer.

Sixteen of 19 enrolled patients with minimal residual disease of ovarian cancer (macroscopic disease < 5 mm or positive blind biopsies and/or positive peritoneal washing), demonstrated by surgical second-look, underwent intraperitoneal radioimmunotherapy (RIT) with the radiolabelled monoclonal antibody I-131 MOv18 (mean dose 14 mg of MOv18 with 3700 GBq of I-131) 30-40 days after the second-look procedure. Clinical follow-up and/or third-look evaluation performed 90 days after RIT showed complete response (CR) in 5 patients, no change (NC) in 6 patients and progressive disease (PD) in 5 patients. Follow-up study showed long-term maintained CR in 1 patient (34 months) and relapses in the other 4 patients after a mean disease-free period of 10.5 months. 5 NC patients showed clinical or instrumental progression after a mean disease-free period of 13 months. The toxicity of RIT was negligible. Only 1 patient showed mild and transient bone marrow suppression (platelet count nadir 52,000 mm3 after 30 days). HAMA production was demonstrated in 94% (15/16) of patients. In conclusion, RIT appears to be a very promising therapeutic approach to treat minimal residual disease of ovarian cancer.

Somatostatin receptor imaging of small cell lung cancer (SCLC) by means of 111In-DTPA octreotide scintigraphy.

Somatostatin receptors have been described on the membrane of neoplastic cells derived from the APUD system and their expression has also been demonstrated on small cell lung cancer (SCLC) in vitro and in vivo. 21 patients with SCLC were studied using 111In-octreotide (111In-OCT) scintigraphy. Scintigraphic examinations were performed following intravenous (i.v.) injection of 111 MBq 111In-OCT with whole-body scintigraphy and planar scintigraphy of the thorax as well as the SPET technique. No short-term side effects were described following 111In-OCT administration. We studied the 111In-OCT biodistribution in 3 patients with serial scintigraphies at 1, 5 and 24 h. We used the 5 h as standard scanning time for the following 18 patients. The scintigraphic results were compared with those of other conventional diagnostic procedures. 111In-OCT detected 86% (48/56) of the lesions already known at the time of scintigraphy. It was positive in all 20 SCLC patients and negative in one lung adenocarcinoma. 111In-OCT showed high sensitivity for mediastinal metastases (94%) and good sensitivity for bone metastases (75%) and abdominal lymph node metastases (71%). 111In-OCT did not detect two liver metastases. 111In-OCT detected five unknown lesions which were confirmed by other diagnostic examinations. 111In-OCT was also effective in cancer patients with low levels of NSE. Our study shows that 111In-OCT scintigraphy is a reliable, non-invasive technique to detect primary SLCL and its locoregional or distant metastases. The clinical utility of receptor status characterisation obtained with 111In-OCT scintigraphy should be evaluated by means of an appropriate prospective study.

111In-octreotide uptake in granulomatous and tumor lesions in a patient with small-cell lung cancer.

A case of a patient with small cell lung cancer and right submandibular node enlargement due to granulomatous lymphadenitis is presented. Diagnostic procedures included: biopsy of the cervical node, transmission computed tomography of the chest, bronchoscopic examination and biopsy of the pulmonary lesion. The patient underwent 111In-octreotide scintigraphy (whole body and single photon emission tomography) which revealed both lesions. We conclude that granulomatous lesions are to be considered as a possible cause of false positive results, when octreotide scintigraphy is used to evaluate distant metastases in patients with known cancer.

Scintigraphic detection of melanoma metastases with a radiolabeled benzamide ([iodine-123]-(S)-IBZM).

UNLABELLED: Iodine-123-(S)-2-hydroxy-3-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl) methyl] benzamide ([123I]-(S)-IBZM) is a radiolabeled benzamide usually employed to study neuropsychiatric disorders, such as schizophrenia and Parkinson's disease. The ectodermic origin of melanocytes and the presence of melanin in the substantia nigra are the theoretic basis of the experimental use of this class of tracers for melanoma imaging. METHODS: Eleven patients with proven metastatic melanoma entered the study. Whole-body and planar scintigrams were performed 2, 4 and 24 hr after intravenous injection of a mean tracer activity of 205 MBq. The dosimetric evaluation was performed by the Medical Internal Radiation Dose Committee method. RESULTS: The [123I]-(S)-IBZM scans allowed the detection of all six cutaneous lesions, five of six superficial pathologic lymph nodes, four of five pulmonary and one of two hepatic metastases. The maximum tumor-to-background ratio was 2.6 in planar images. The hepatobiliary excretion of the tracer may limit detection of intra-abdominal lesions. Dosimetry is similar to data for nononcologic patients. CONCLUSION: Although it is unclear if the mechanism of radiopharmaceutical uptake in melanoma is due to binding to membrane receptors or due to interactions with intracellular structures, radiolabeled benzamide is a promising tracer to detect melanoma.

Comparison of radioimmunodetection with other imaging methods in evaluating local relapses of colorectal carcinoma.

BACKGROUND: The prognosis for colorectal cancer patients is related closely to the extent of tumor at the time of diagnosis, and early detection of metastatic or recurrent disease is an important prerequisite for successful treatment. Radioimmunodetection is a relatively new technique to image colorectal cancer using radiolabelled monoclonal antibodies (MoAb). The goal of this study was to evaluate the clinical use of radioimmunodetection with the anti-carcinoembryonic antigen MoAb FO23C5, radiolabelled with 131I, in patients submitted to surgery for colorectal cancer and with suspected local recurrences. The results of radioimmunodetection were compared with those of computed tomography, ultrasonography, magnetic resonance imaging, and other diagnostic techniques (gastrointestinal x-ray, endoscopy, and, in selected cases, a surgical second look). METHODS: Fifty-nine patients with a rise in carcinoembryonic antigen serum levels or a clinical suspicion of recurrences entered the study. Scintigraphy was performed at multiple interval times (4-100 hours) after an intravenous injection of radiolabelled FO23C5 F(ab')2 fragments. RESULTS: The cumulative results showed the high sensitivity (89%), specificity (78%), and accuracy (86%) of radioimmunodetection. Of the radiologic methods, only magnetic resonance imaging had the same accuracy (86%), with lower specificity (64%) and higher sensitivity (93%). Computed tomographic scan and ultrasonography displayed the poorest accuracy (68% and 47%, respectively). CONCLUSIONS: Radioimmunodetection is an important imaging technique that can be used in clinical practice for the follow-up of the patient with colorectal carcinoma.

Current role of gallium scan and magnetic resonance imaging in the management of mediastinal Hodgkin lymphoma.

BACKGROUND: A residual mediastinal mass after treatment represents a common diagnostic problem in the management of patients with Hodgkin lymphoma (HD). Conventional diagnostic radiology, computed tomography (CT), or ultrasonography (US) do not adequately reflect changes as fibrosis or necrosis. Gallium-67 (67Ga) imaging has been proven to be useful for the evaluation of HD in the mediastinum. The authors compared the ability of gallium scan and magnetic resonance imaging (MRI) to evaluate the mediastinal disease in the follow-up of patients with HD. METHODS: Thirty-four patients previously treated for HD were investigated with gallium scan, MRI, and all the other investigations to evaluate the mediastinal region. Sixteen patients were in restaging after treatment, and 18 were investigated for suspected radiologic recurrence in the mediastinum (follow-up, 9-75 months). The results of gallium scan and MRI were matched with clinical findings during the follow-up. RESULTS: A sensitivity of 85.7% for 67Ga and 92.8% for MRI was found, while the specificity was 100% for the scan and 80.6% for MRI. The predictive positive value that resulted was 100% for 67Ga and 68.4% for MRI. CONCLUSIONS: Both examinations were accurate in assessing the activity of residual masses in the mediastinum after treatment. 67Ga showed a lower sensitivity in comparison with MRI, but 67Ga frequently overestimates the presence of pathologic tissue. The authors acknowledge the complementary role of these two tests, but if only one of these examinations can be performed for logistic or economic reasons, then gallium scan represents the single most adequate diagnostic procedure.

Enhancement of in vivo monoclonal antibody targeting with recombinant interferon and cytokines.

Up to now a number of studies have been performed to determine whether the combined use of cytokines and monoclonal antibodies (MAbs) directed against tumor-associated antigens (TAA) can increase the sensitivity of radioimmunoscintigraphy (RIS). It is well known that human natural and recombinant interferons can enhance the cell surface expression of HLA Class I and II antigens as well as some specific tumor antigens, but there is scanty and conflicting information about the expression and shedding of TAA. Some authors reported that alpha-IFN enhances the expression of a melanoma-associated antigen (MAA), recognized by conventional antiserum. Other authors have found no changes in the expression of MAA identified by MAbs. In a pilot study on patients with malignant melanoma Rosenblum demonstrated an increase in tumor uptake of the anti-melanoma MAb 96.5 after IFN administration. In our study we performed immunoscintigraphy with the anti-melanoma MAb 225.28S in the same patient before and after IFN administration in different doses. We point out the difference in biodistribution in different organs and in blood clearance and discuss the possibility to improve the sensitivity of RIS.

Bone scintigraphy in breast cancer: a ten-year follow-up study.

Two-hundred and sixty patients with T2-T3a, pN1, M0 (TNM classification) breast cancer underwent clinical and instrumental follow-up (mean 122 months) including periodic bone scintigraphy. A total of 1971 scintigraphic examinations were performed (range 3 to 15 scintigraphies/patient, mean 8). The results of scintigraphy were compared to standard radiographs and to the clinical history of the patients. Bone metastases occurred in 71% of 122 patients who suffered from tumor recurrence during the study. Bone lesions (alone or associated with other tumor lesions) represented the most common site (42%) of first tumor relapse and occurred as first site of distant metastases in 11% of 29 patients with locoregional relapse. Bone metastases were symptomatic in 41% of cases. The sensitivity and specificity of bone scintigraphy were 98% and 95%, respectively; the positive and negative predictive values were 73% and 100%; the accuracy was 96%. Scintigraphic false positive results occurred particularly in the skull and in the ribs and generally when the examination detected less than three focal abnormalities. This study demonstrates that the number of positive scintigraphies during follow-up increases over the years, reaching a plateau only at approximately 8-10 years. It is therefore not advisable to stop performing bone scintigraphies after the first years of follow-up as this may lead to the loss of important information.

Pilot, multicenter and prospective trials with an anti-CEA antibody.

In this paper we summarize the investigations performed by our group utilizing an anti-CEA monoclonal antibody (F023C5) labelled with different radionuclides in humans. Since 1983 radioimmunoscintigraphy (RIS) was performed on 51 patients with 64 localizations of colo-rectal carcinoma (pilot study). A multicenter clinical trial in a large number of patients (509 pts of which 284 with gastrointestinal cancer) was subsequently carried out in collaboration with ten nuclear medicine centres. High sensitivity and specificity values were obtained by these studies and many unsuspected lesions were recorded. In order to better define the clinical role of RIS, a prospective study was performed on 59 patients with suspected local relapses of colo-rectal cancer. A comparative evaluation of RIS, CT scan, US and MRI was done. RIS and MRI had the highest accuracy (86%) followed by CT scan (68%) and US (54%).

The role of serum carcinoembryonic antigen (CEA) in the management of patients with colorectal carcinoma: the experience of the Istituto Tumori of Milan.

CEA determination has attained an important role in the clinical management of patients with tumors of the colorectal tract. In this paper the experience of the Istituto Tumori of Milan is reviewed and the results are discussed. Three hundred and thirty-six patients were followed after curative resection of colorectal carcinoma. The follow-up period was 15 years, from January 1975 to December 1990 (global follow-up 1358 years). In the course of follow-up 136 patients developed recurrent disease. The number of CEA determinations for each patient ranged from 1 to 37 (mean 8, total 3330). CEA levels of presurgical patients were related to the clinical stage. Among patients who developed recurrences 61% showed an increase in CEA serum levels. In 200 patients with a negative follow-up we observed only 15 cases of false-positive results.

Single determination of CA 15.3 and bone scintigraphy in the diagnosis of skeletal metastases of breast cancer.

Single determination of CA 15.3 and bone scintigraphy were performed on the same day as follow-up procedures in 864 patients with breast cancer. The sensitivity and specificity of bone scintigraphy for skeletal metastases were 99% and 88.8%, respectively. The overall sensitivity and specificity of CA 15.3 (cut-off for pathological values greater than 30 U/mL) for cancer recurrence or distant metastases were 69.2% and 92.1%, respectively. The sensitivity of CA 15.3 for bone metastases was lower (69.4%) than that of bone scintigraphy. This was mainly due to the relatively high proportion of false-negative CA 15.3 levels in patients with 1-2 bone metastases (sensitivity = 33.3%). According to this result, the circulating levels of CA 15.3 showed a good correlation with tumor extension and, in patients with bone metastases, with the number of skeletal lesions. As regards the contribution of CA 15.3 to the diagnosis of bone metastases, the demonstration of elevated CA 15.3 values in patients with positive bone scintigraphy could support the diagnosis of skeletal metastases. In fact, the positive predictive value of CA 15.3 in patients with positive bone scintigraphy was significantly higher than with only bone scintigraphy (53.8%) or CA 15.3 (50.4%). Finally, very high values of CA 15.3 in patients with known bone metastases could indicate the presence of visceral metastases (mean CA 15.3 in patients with bone metastases = 125.8 U/mL; mean CA 15.3 in patients with bone and visceral metastases = 420.5 U/mL).

Experience with palliative [131I]metaiodobenzylguanidine therapy in advanced neuroblastoma.

Our experience with palliative [131I]metabenzylguanidine (131I-MIBG) therapy in 7 patients (6 children and 1 adult) affected by advanced neuroblastoma is reported. All patients (classified as IV stage) showed a progression following initial intensive therapy, including chemotherapy and, in some cases, hemi-body irradiation and surgery for their primary tumor. 131I-MIBG activity ranged for a single course between 2.77 GBq to 5.55 GBq on the basis of age, intensity of uptake, and the hematological assessment. Four patients received only one course of therapy due to progressive disease (2), early death (1) or persistent thrombocytopenia unrelated to 131I-MIBG therapy (1). Two patients received two courses and showed a partial response lasting 4 months and stable disease lasting 3 months respectively. Therapy was thereafter discontinued due to progression. One patient received 4 courses of therapy (cumulative activity = 19.61 GBq) in 5 months. A partial response for 9 months in the bone metastases was documented, but the therapy was discontinued due to persistent thrombocytopenia (58,000 plts/microL) lasting 4 months. Thrombocytopenia was the major side-effect, occurring in 5/7 patients over 8 courses of therapy for a mean period of 37 days (7-120 d). Thus, in our experience thrombocytopenia is the major factor limiting the therapeutic effect of 131I-MIBG therapy in palliative treatment.

[131I]metaiodobenzylguanidine therapy in paraganglioma.

Our experience with [131I]metaiodobenzylguanidine (131I-MIBG) therapy in a 10 year old boy is reported. At disease onset, in May 1988, this boy presented a large mass in the upper left abdominal quadrant, which was resected with a histopathological diagnosis of extra-adrenal malignant pheochromocytoma (paraganglioma). He subsequently underwent two further surgical resections and chemotherapy. When 131I-MIBG therapy was started, in June 1990, skeletal and abdominal metastases were present. These localizations were revealed by 131I-MIBG scans and confirmed by x-ray examination. At present 6 courses of therapy have been performed with a cumulative activity of 29.6 GBq. Side-effects have been limited to vomiting and mild thrombocytopenia, lasting 2 weeks during the second course of therapy. After 15 months of therapy, a progressive reduction of MIBG uptake, coupled with a stabilization of the lythic lesions, has been observed.

[131I]metaiodobenzylguanidine therapy in carcinoid tumors.

Our experience with [131I]metaiodobenzylguanidine (131I-MIBG) therapy in two patients with carcinoid tumor is described. These patients were selected because of multiple areas of uptake on 131I-MIBG scan, consistent with the extent of the disease. Both patients presented diarrhea and liver metastases. Para-aortical lymphonodes and skeletal metastases were present in the first and the second patient, respectively. Previous treatment involved r-alpha-interferon, surgery or radiotherapy. In both cases 131I-MIGB therapy was started in December 1990 and is still continuing. No haematologic or hepatic side-effects have been observed. Mild hypotension (90/60 mmHg) occurred in one patient during the first course of therapy and was resolved by corticoid treatment. A stabilization of disease and a progressive reduction of diarrhea have been observed in both patients. In the second patient an initial decrease in liver metastases was confirmed by ultrasonography 7 months after the beginning of therapy.

[Angiocardioscintigraphy in the cardiological surveillance of chemotherapy with anthracyclines]. / La angiocardioscintigrafia nella sorveglianza cardiologica della chemioterapia con antracicline.

Equilibrium angiocardioscintigraphy is a noninvasive nuclear medical method which allows cardiac function to be assessed. It is widely used in oncology since some clinically important drugs used in antitumor chemotherapy have a marked cardiotoxic effect. Angiocardioscintigraphy enables several parameters characteristic of cardiac function to be assessed, namely the left ventricular ejection fraction whose alterations during chemotherapy allow possible cardiotoxic side effects to be revealed before the development of irreversible heart failure.

Immunoscintigraphy of colorectal carcinoma with an anti-CEA monoclonal antibody: a critical review.

An anti-CEA monoclonal antibody (FO23C5), belonging to the IgG1a class, was used to perform several preclinical and clinical studies on radioimmunoscintigraphy (RIS) in patients with colorectal carcinoma. Preliminary screening on different tissues showed high specificity of this antibody for gastric and colorectal carcinomas. A pilot study on 51 patients with 64 localizations of colorectal carcinoma was realized, followed by a multicenter validation study in which, among 509 patients bearing CEA secreting tumors, 254 patients had primary or relapsed colorectal tumors. High sensitivity and specificity values were obtained by these studies and many "unsuspected" localizations were recorded. In order to better define the clinical utility of this approach, a prospective trial was run on 59 patients previously submitted to surgery for colorectal carcinoma and with suspected local relapses. A comparative evaluation of RIS, CT scan, US and MRI was performed. RIS and MRI have the highest value of accuracy (86%) followed by CT scan (68%) and US (54%). No adverse reactions were noticed in any of the patients examined.

Radioimmunoscintigraphy of ovarian cancer with the MOv18 monoclonal antibody.

The monoclonal antibody (Mab) 131I-MOv18 was administered to 30 patients with ovarian carcinoma intravenously (n = 20) and intraperitoneally (n = 10). After intraperitoneal administration, higher tumour uptake (mean values 1.3% vs. 0.8%) and a better tumour/background ratio (mean values 2.8 vs. 1.9) than after intravenous injection were obtained. Moreover, after intraperitoneal administration the uptake in non-affected organs, such as liver and spleen, was lower. However, occasionally the favourable results of the intraperitoneal route were cancelled by persistent pelvic non-specific accumulations of 131I-MOv18. The possibility to change the biodistribution pattern in the latter cases with peritoneal washing was evaluated. 3 patients were submitted to this procedure and an improvement in the radiotracer biodistribution was obtained in 1 case. With regard to tumour detection, the average sensitivity (73%) showed a significant difference from the sensitivities for abdominal (61%) and pelvic lesions (90%). No false positive results were noted.

Clinical protocols for the application of tests for circulating tumor markers.

Circulating marker level determination in clinical practice requires an adequate strategy of application, in view of the particular features of the parameter related to the marker. The test result, which is usually expressed in terms of concentration, cannot be considered as an absolute value because every biochemical tumor indicator expresses an activity of the tumor which generally leads to increased levels of a "normal" substance in blood or biological liquids. Therefore, the result should be interpreted as a dynamic variation occurring in time, and should always be related to a previous reference value. This means that marker determination in clinical practice should be repeated periodically, both for the evaluation of tumor response to treatment and for the detection of recurrence after radical surgery. A single measurement at the time of disease presentation can characterize the tumor with regard to its capacity of producing the signal, and consequently regarding its extent and growth. These laboratory findings are of no value whatever if they are not integrated with all the other available clinical and instrumental data concerning the neoplasm; only then can they provide useful additional information. Also, all biological variables should be taken into account which may affect circulating marker levels independently of the history of the tumor such as sex, age, clearing organ function, race, alcohol and tobacco habits, concomitant diseases. These procedural protocols should be outlined and codified for each individual neoplasm since it is useless to work with scattered data which are not ordered in some kind of procedural logic.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical value of radioimmunoscintigraphy in the follow-up of ovarian carcinoma: a prospective study.

Twenty-five patients treated with debulking surgery and chemotherapy for ovarian cancer were prospectively studied to evaluate the efficacy of radioimmunoscintigraphy (RIS) in detecting residual tumor before second-look surgery. RIS was performed with the monoclonal antibody OC125 F(ab')2 labelled with I-131 without knowledge of clinical data and compared with subsequent surgical results. Second look showed tumor persistence in 12 patients, mostly characterized by small lesions. The overall diagnostic sensitivity of RIS was 50% and the specificity was 85%. In particular, RIS showed better sensitivity for pelvic tumor localizations than for abdominal sites (73% vs 33%); this was due to the inability of RIS to detect upper abdominal lesions. Therefore, our conclusion is that, at present, RIS cannot substitute surgical second-look in the management of ovarian cancer, however, considering that also ultrasonography, computer tomography and magnetic resonance are not always able to give definite diagnostic evidence in the follow-up of ovarian carcinoma, RIS could be added to these procedures to balance the limitations of each method. In this regard, the best application of RIS could be in the follow-up of patients with marker elevation without clinical evidence of disease, especially in the case of pelvic fibrosis or adhesions due to previous therapy, where the other non-invasive tools can give doubtful diagnostic results.