Role of 131I-labelled anti-CEA/CA 19-9 monoclonal antibodies in the diagnosis and follow-up of gastrointestinal tumors.
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Antibodies, Monoclonal↗
Biomedical subjects
V Rufini
Publications and source records attributed to V Rufini.
131I-metaiodobenzylguanidine in the treatment of neuroblastoma at diagnosis.
Radioactive metaiodobenzylguanidine (131I-MIBG) is taken up specifically by neuroblastoma cells and appears to represent a new treatment modality in patients with advanced neuroblastoma. Taking into account the fact that all patients so far treated were heavily pretreated and resistant to chemotherapy, the results obtained appear encouraging. In order to explore further the potential role of this new drug in untreated patients, we treated with 131I-MIBG a child with stage III neuroblastoma at diagnosis. We observed the complete disappearance of a large abdominal tumor mass after a relatively low dosage of 131I-MIBG, with minimal hematologic toxicity. No further treatment was given and, at present, the patient is alive with no evidence of disease 18 months from diagnosis. This child represents, to our knowledge, the only case of neuroblastoma thus far treated at diagnosis and the excellent response obtained suggests the need for further investigations of this therapy in untreated patients.
3-Iodobenzylguanidine↗
Diagnostic and therapeutic potential of new radiopharmaceutical agents in medullary thyroid carcinoma.
Recently developed radiopharmaceuticals have been proposed for imaging medullary thyroid carcinoma (MTC) with some having therapeutic potential. This study compares the imaging results obtained with radioiodinated meta-iodo-benzylguanidine (MIBG), 99mTc (V) DMSA, and 131I F(ab')2 anti-carcinoembryonic antigen (anti-CEA) in a group of MTC patients. In 23 patients 131I MIBG imaging showed a high specificity (no false-positive results) but a less satisfactory sensitivity (50%). In 12 patients 99mTc (V) DMSA revealed a better sensitivity (77%) but a lower specificity (three false-positive results). Positive results were obtained in two of three patients studied with 131I F(ab')2 anti-CEA. These data suggest that the highly sensitive 99mTc (V) DMSA should be considered as a first choice procedure followed by the highly specific radioiodinated MIBG to confirm the initial results. Since radioiodinated MIBG imaging may have therapeutic usefulness, 131I MIBG was evaluated in an integrated treatment protocol in four cases of proven MTC. The preliminary results obtained were encouraging.
3-Iodobenzylguanidine↗
The possible use of radioiodinated metaiodobenzylguanidine (MIBG) in medullary thyroid carcinoma.
The value of radioiodinated metaiodobenzylguanidine (MIBG) in imaging thyroid medullary carcinoma (MTC) was investigated (18 studies) in 12 patients with proven MTC. Calcitonin (CT), carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) were also determined. The patients were divided into two groups. Group I comprised 7 patients who had relapsed; two of them were also studied before total thyroidectomy. In the 2 cases studied before total thyroidectomy 123/131I-MIBG imaged the primary tumor (partially) and the residual tumor involved lobe. The residual/recurrent tumor present in 4 and some of the remote metastases in 3 out of 5 were detected. Group II includes 5 patients studied postoperatively with no evidence of disease. A residual tumor in one of the 2 patients without evidence of disease on the basis of conventional diagnostic modalities but with elevated tumor markers was visualized; the outcome was correctly negative in 3. One patient underwent treatment with 131I-MIBG. A total dose of 27.1 GBq (733 mCi) was given. Relief of pain and partial regression of the lesions was achieved.
3-Iodobenzylguanidine↗
[A comparison of scintigraphy with radioiodinated MIBG and CT in localizing pheochromocytomas].
In order to define the diagnostic roles of MIBG imaging and CT in the detection of pheochromocytomas (pheos), the results obtained in 45 patients suspected of bearing pheo and studied with both modalities were analyzed and compared. Scintigraphy was correctly negative in 22/23 cases, correctly positive in 11/12 adrenal and 5/5 extra-adrenal pheos, and in 4/5 malignant pheos (metastases present in 2 cases were also identified). CT was correctly negative in 20/23 cases (a mass other than a pheo was detected in 3 patients); correctly positive in 12/12 adrenal and 4/5 extra-adrenal pheos and in 5/5 malignant pheos. Sensitivity, specificity and accuracy of scintigraphy and CT were 91% and 95.4%, 95.6% and 87%, 93.3% and 91.1% respectively (differences were not statistically significant). The overall data emphasize the complementary role of 123/131I-MIBG imaging and CT in the location of pheochromocytomas. A flow-chart essentially grounded on the combined use of both these diagnostic modalities is proposed which includes 123/131I-MIBG scintigraphy as a first choice examination.
3-Iodobenzylguanidine↗
Treatment of neuroblastoma with 131I-metaiodobenzylguanidine.
Seven patients with neuroblastoma (six children and one adult) were treated with therapeutic doses of high specific activity 131I-metaiodobenzylguanidine (131I-MIBG). Six patients were in stage IV and unresponsive to conventional treatment. One patient, in stage III, was treated at diagnosis, an approach never previously reported. Single doses of 131I-MIBG varying from 70 to 184 mCi split into two parts were administered by slow i.v. infusion (4 to 8 hours) at 2- to 4-day intervals. The following results were obtained in the six evaluable patients: two patients showed transient stabilization of the disease; three had an objective response, with shrinking of the primary tumor and/or regression of the metastatic lesions. Of these three patients, two suffered relapses at 2 and 7 months, respectively, from the first course of MIBG. The third patient, in whom the residual disease almost completely disappeared following MIBG therapy, is still alive in complete remission after autologous bone marrow transplantation with a follow-up of 14 months. The single patient treated at diagnosis showed a dramatic response to a relatively low dosage of MIBG, with histologically proved disappearance of the tumor mass. Our data indicate that MIBG may be useful in the treatment of neuroblastoma unresponsive to conventional chemotherapy. The complete response observed in the patient treated at diagnosis suggests that the full potentiality of MIBG therapy should be explored in untreated patients.
3-Iodobenzylguanidine↗
[A new medico-nuclear outlook for the diagnosis and treatment of pheochromocytomas: 131I-meta-iodobenzylguanidine (131I-MIBG). Comments on results obtained].
The diagnostic and therapeutic potential of 131I-MIBG, the new imaging agent with structural similarity to norepinephrine, was evaluated in 23 patients with a suspect pheochromocytoma. Seven out of 8 benign pheochromocytomas (2 ectopic) were correctly localized with 131I-MIBG scintigraphy (1 false negative). In 2 catecholamine-secreting malignant pheochromocytomas both the primary tumor and the metastases (1 case) were demonstrated. One uncommon case of dopamine-secreting malignant pheochromocytoma, as expected, was not shown. In the remaining 12 cases, found to be "normal" after completing the work-up, distribution of the radiopharmaceutical was evaluated using a semiquantitative grading system. 131I-MIBG scintigraphy proved to be a non invasive and accurate (95%) diagnostic modality, specific for neuroadrenergic tumors. The treatment with 131I-MIBG was also carried out in 2 malignant pheochromocytomas with encouraging results.
3-Iodobenzylguanidine↗
[Possibility of using 131I-meta-iodobenzylguanidine in the diagnosis of neuroendocrine tumors differing from pheochromocytomas].
The results obtained using 131I-MIBG to diagnose different neuroendocrine tumors in 17 patients are discussed. In 8 of the neuroblastomas studied the examination gave a wide spectrum of scintigraphic results according to the various stages of evolution of the tumors, thus supplying additional useful information for metabolic treatment. Contradictory data were obtained in 5 cases of medullary cancer of the thyroid. The overall results were unexpectedly negative for 2 carcinoid tumors and, as expected, negative for 2 ganglioneuromas. These data confirm that 131I-MIBG is a non invasive, reliable and easy-to-perform technique which is no longer limited to the diagnosis of pheochromocytomas, but can also be used for the diagnosis of other tumors derived from neural crest cells.
3-Iodobenzylguanidine↗
Scintigraphic localization of a disseminated malignant pheochromocytoma with the use of 131I-meta-iodobenzylguanidine.
Preliminary clinical studies with 131I-meta-iodobenzylguanidine, a newly synthesized radiopharmaceutical and guanethidine analog capable of imaging the adrenal medulla, have led to the identification of a case of disseminated malignant pheochromocytoma with the localization of brain and bone metastases. The result is of particular interest as the symptomatology in this case appeared rather equivocal and various investigations had led to a completely different diagnosis. This new scintigraphic technique has proved to be safe, specific and noninvasive, and it may have a clinical application as a complementary or alternative technique to conventional diagnostic tests.
3-Iodobenzylguanidine↗
Diagnostic imaging of the thyroid: methodology and normal patterns.
The diagnostic imaging of the thyroid is based on sonography and scintigraphy, which to-date play a unique role in the morphofunctional study of the thyroid gland. The high spatial resolution of sonography allows an accurate evaluation of the thyroid morphology, size and parenchymal structure. Color Doppler sonography allows a qualitative assessment associated with quantitative parameters of glandular vascularization. Furthermore, sonography is the simplest procedure to achieve an accurate, reproducible measurement of thyroid volume. Scintigraphy provides information unavailable by other methods on the regional thyroid function. The most common tracer for thyroid scintigraphy is 99mTc pertechnetate. 123I and 131I are essential for radioiodine uptake test. CT and MRI, while invaluable for other organs and apparatus, play a limited role in the diagnosis of thyroid disease.
Diagnostic Imaging↗
Diagnostic imaging of euthyroid goiter.
In diffuse or nodular euthyroid goiter, diagnostic imaging is indicated to define, by sonography, the morphology, size and structure of the goiter and to evaluate, by scintigraphy, the regional thyroid function. The instrumental diagnosis of thyroid nodule is essentially based on sonography, scintigraphy and (US-guided) needle aspiration cytology. The evaluation of some sonographic findings (echogenicity, calcification, lesion margins and presence of peripheral ring) may direct to the differentiation of a benign or malignant lesion. The role of color Doppler in the characterization of thyroid nodules is still controversial. Scintigraphy provides information on nodular function, being also the only exam able to show the presence of autonomously functioning thyroid tissue ("hot" nodule), whose diagnosis allows to rule out the presence of thyroid carcinoma with a very strong probability. In intrathoracic goiter, CT and MRI and indicated to show the continuity with the cervical thyroid and to define the relationships with adjacent structures. Radioiodine scintigraphy shows with high (> 90%) diagnostic accuracy the thyroid nature of a mediastinal mass (plunging goiter).
Diagnostic Imaging↗
Diagnostic imaging in thyrotoxicosis.
In thyrotoxicosis, imaging mainly scintigraphy, color Doppler sonography and radioiodine uptake test are used in the differential diagnosis as well as in the morphofunctional evaluation of the thyroid before and after therapy (mainly pharmacological or with radioiodine). Radioiodine uptake test differentiates high uptake thyrotoxicosis (Graves'disease, toxic nodular goiter) and low uptake thyrotoxycosis (subacute or silent thyroiditis, ectopic thyrotoxicosis, iodine-induced hyperthyroidism). In Graves'disease scintigraphy shows thyroid enlargement with intense homogeneous tracer uptake; rarely nodules with no uptake are present. On color Doppler sonography, a part from enlargement, typical findings are: diffuse structural hypoechogenicity (at times with echoic nodules), parenchymal hypervascularization ("thyroid inferno"), high systolic velocities (PSV > 70-100 cm/sec) in inferior thyroid arteries. Scintigraphy is the only method able to evidence an autonomously functioning thyroid nodule and stage it (in association to clinical findings and TSH, FT3, FT4 determination) as: toxic, non toxic (or pretoxic) and compensated, depending on whether there is inhibition of extranodular tissue. A scintigraphically "hot" nodule appears hypervascularized on color Doppler sonography (especially in the toxic or pre-toxic phase) with high PSV (> 50-70 cm/sec) in the ipsilateral inferior thyroid artery. The most reliable parameters in the evaluation of the therapeutic efficacy are: decreases in thyroid (Graves'disease) or nodular (autonomously functioning nodule) volume; decreased radioiodine uptake (Graves'disease); functional recovery of suppressed parenchyma (autonomously functioning nodule); decreased PSV in the inferior thyroid arteries.
Diagnosis, Differential↗
Liver metastases of endocrine tumour associated with multiple endocrine neoplasia type 1: a sustained response to interferon therapy or a peculiar benign course?
The authors describe the case of a 51-year-old male with Zollinger-Ellison syndrome manifested by epigastralgia, nausea, vomiting, hypergastrinemia and multiple endocrine neoplasia type 1. History included a Billroth II procedure for a perforated duodenal ulcer. Multiple metastatic liver lesions were found that were gastrin-negative and chromogranin-positive. Endoscopy revealed a large ulcerated gastro-jejuno-colonic fistula which was surgically repaired. Pre- and postoperative imaging studies, including the highly sensitive somatostatin-receptor scintigraphic scan using In-pentetreotide, have consistently failed to disclose other tumors. Recent reports indicate that most Zollinger-Ellison syndrome-associated gastrinomas are small, easily overlooked lesions located in the proximal duodenum rather than in the pancreas as formerly believed. In the present patient therapy with omeprazole and alpha-interferon has produced complete remission of the Zollinger-Ellison syndrome and a stabilization of tumor growth has occurred during the last 7 years, allowing the patient to live a normal life. This peculiar response to therapy is discussed.
Humans↗
Diagnostic imaging of differentiated thyroid carcinoma.
The role of diagnostic imaging in differentiated thyroid carcinoma is analyzed. 99mTc-pertechnetate 123I and 131I scintigraphy allows the evaluation of nodules with their differentiation in cold (hypofunctioning) and hot (functionally autonomous) nodules; thyroid carcinomas are cold nodules even if most of them are benign. On sonography thyroid nodules are well visualized with the definition of their site, number, size (not very useful parameters for the diagnosis of malignancy), echoic structure, and vascularization on color Doppler. The sonographic findings suggestive of differentiated thyroid carcinoma are: solid and hypoechoic structure, irregular ill-defined margins, absent or discontinuous peripheral ring, microcalcification, intranodular vascularization, local lymphadenopathies. These findings are characteristic but not pathognomonic, mostly for papillary carcinoma, while in the frequently isoechoic follicular carcinoma microcalcification and lymph node metastases are rare. Only the finding, although rather infrequent, of the dissemination to adjacent structures (muscles and vessels) is a definite indication for malignancy of a thyroid nodule. Color Doppler sonography plays a major role in the postoperative staging and follow-up, in combination with thyroglobulin determination and 131I whole body scintigraphy and it allows the detection of local and/or laterocervical lymph node recurrence. The most typical sonographic findings of metastatic lymphadenopathy are the roundish shape (length/anteroposterior diameter ratio-L/A < 1.5), not visible or displaced nodal hilum, thickened cortical layer with echoic structure similar to that of thyroid parenchyma, at times with microcalcification, cortical vascularization and dismantled angioarchitecture. CT and MRI are occasionally more useful to evaluate the substernal or retrosternal extension of voluminous thyroid masses and to identify local or distant metastases.
Carcinoma↗
Radioiodine therapy in differentiated thyroid carcinoma.
Radioiodine therapy has been successfully applied for over 50 years in the management of differentiated thyroid carcinoma. Careful patient preparation and selection of the optimal dose of radioiodine to be administered are two factors of major importance in the course of management. Main indications for 131I therapy are the ablation of residual thyroid tissue after thyroidectomy, the treatment of locoregional recurrence and distant metastases which involve almost exclusively the lung and bones. A controversial aspect is that of patients with high serum TG levels but negative whole body 131I scintigraphy for whom there is no general agreement. Other controversial aspects involve ablation therapy as the selection of patients to be treated and the control of its efficacy. The cost and possible adverse side-effects of 131I therapy require a careful analysis of prognostic factors in each patient candidate for the treatment.
Carcinoma↗
Diagnostic approach, genetic screening and prognostic factors of medullary thyroid carcinoma.
Medullary thyroid carcinoma is the least frequent thyroid neoplasm; it originates in thyroid parafollicular cells (calcitonin secreting C cells). In 80% of cases it is sporadic, in the remaining 20% it is familial, associated or not to other endocrinopathies as pheochromocytoma and hyperparathyroidism (MEN 2A, MEN 2B, and isolated familial medullary thyroid carcinoma). Preclinical diagnosis in relatives of affected subjects (preferably at pediatric age) is essential for successful therapy and is performed with genetic and biochemical screening tests. The genetic screening is based on DNA analysis (RET proto-oncogene mutations) of the patient, and if positive of all first degree relatives, to separate sporadic (somatic mutations) from familial (germline mutations) forms. The biochemical screening is based on calcitonin determination and its increase after pentagastrin stimulation, (a peculiar characteristic of medullary thyroid carcinoma, the first biochemical disorder in a subject at risk) and is mainly used in genetically silent familial medullary thyroid carcinoma. The principal negative prognostic factors of medullar thyroid carcinoma and the debate concerning the use of calcitonin determination in the diagnosis of the "cold" thyroid nodule have been analyzed.
Algorithms↗
Role of nuclear medicine in the diagnosis and therapy of medullary thyroid carcinoma.
Medullary thyroid carcinoma (MTC) originates in the parafollicular cells (C cells) of the thyroid, secreting both calcitonin and CEA. Genetic and biochemical testing allow early pre-clinical identification of familial forms. Sporadic MTC usually presents as a solitary palpable thyroid nodule and in most cases the definitive diagnosis is established only at the time of surgery. Nuclear medicine procedures, which play a minor role in the preoperative evaluation of MTC, are essential in postoperative follow-up to detect residual and/or recurrent tumor. A number of radiopharmaceuticals are able to visualize MTC lesions with considerable advantages in diagnosis and prognosis, some of them having also a therapeutic role. Among them, 99mTc[V]DMSA shows the highest diagnostic sensitivity and is considered by many authors the radiopharmaceutical of choice in the postoperative work-up of MTC. Radioiodinated MIBG, in spite of its high specificity has a poor sensitivity (30%); however it is useful for the identification of pheochromocytoma and, in patients showing MIBG uptake in tumoral lesions, high activities of 131I-MIBG may be used for therapy. 111In labeled octreotide detects lesions which express somatostatin receptors; a positive scintigraphic result seems to give also prognostic information (higher uptake in slow-growing lesions) and provides the basis for treatment with octreotide or lanreotide and 111In or 90Y-labeled octreotide analogues. Interesting perspectives are offered by 18F-FDG PET and monoclonal anti-CEA labeled antibodies; the latter may be also used for therapy.
Carcinoma↗
Incidentalomas: problems of diagnostic assessment.
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Adenoma↗