Treatment of malignant pheochromocytoma with [131I]metaiodobenzylguanidine: a French multicenter study.

Six Medical Centers in France were involved in a prospective study evaluating the efficacy of [131I]metaiodobenzylguanidine (131I-MIBG) in the treatment of malignant pheochromocytoma. Fifteen patients aged from 28 to 75 years bearing tumor sites demonstrating a good MIBG uptake were included in this study. Catecholamines were elevated in 13/14 cases, VMA in 9/14 and metanephrines in 13/14. Two to 11 therapeutic activities of 131I-MIBG were administered, with a mean number of therapeutic doses per patient of 4 and a mean single activity of 4.7 GBq (range 2.9 to 9.25 GBq). Seven patients were alive, and seven patients died 6 to 29 months after their first MIBG administration (mean follow-up of 36 months); 1 patient was lost to follow-up. Two patients had a partial tumor response only, 4 had a hormonal response only, and 3 had both a partial tumor response and a hormonal response (complete in 2 cases). Six patients did not respond to the treatment, 4 of them died. Of the 9 responding patients, 4 relapsed, 3 of whom died subsequently. Haematological toxicity was always transient and mild, except in 1 case.

Use of m-[131I]iodobenzylguanidine in the treatment of malignant pheochromocytoma.

The efficacy and safety of m-[131I]iodobenzylguanidine ([131I]MIBG) were assessed in 15 patients with malignant pheochromocytomas in a nonrandomized, single arm trial, in which patients were treated with [131I]MIBG (SA, 740 megabequerel/mg) every 3 months. Seven of these patients had bone and soft tissue metastases, 4 had only soft metastases, and 4 had only bone metastases. The follow-up period ranged from 6-54 months; the number of doses ranged from 2-11, with 2.9 (78.4 mCi) to 9.25 gigabequerel (GBq) (250 mCi)/administration and a cumulative activity from 11.1-85.90 GBq (300-2322 mCi). The absorbed cumulative dose in tumors ranged from 12-155 Gy. A beneficial effect of the treatment was observed in 9 patients (60%). No complete remission of the disease was observed. Seven patients died during the study, among whom 4 never responded to the treatment. Seven had hormonal responses (4 complete and 3 partial), with a duration ranging from 5-48 months. Among these patients, 4 relapsed, and 3 died within 3 months. Five patients had partial tumoral responses mainly located in soft tissues and for a duration ranging from 29-54 months. All patients with a hormonal response had objective improvement in clinical status and blood pressure. There was no clear-cut relationship between the cumulative dose and the responses. The main side-effect observed in 1 patient with widespread bone metastases after three doses (12.9 GBq) was a pancytopenia, which resolved after treatment was discontinued. This study suggests that repeated [131I]MIBG treatment could be effective in patients with advanced malignant pheochromocytoma.

Low levels of serum thyroglobulin after withdrawal of thyroid suppression therapy in the follow up of differentiated thyroid carcinoma.

We evaluated the reliability of very low serum thyroglobulin (Tg) levels (less than 3 ng/ml) obtained after withdrawal of thyroid suppression therapy in 224 patients without anti-Tg antibodies, who had undergone total thyroidectomy (125 patients) or thyroidectomy followed by 1 or more courses of 131I therapy (99 patients), by performing whole body scans after a therapeutic course of 131I given at the same time of Tg measurement. In 79 patients (35%) a positive scan, associated with a very low level of Tg, was noted. The 131I uptake was limited to the thyroid bed in 60 patients, but metastases were demonstrated in 19 patients (8.5%). These results are mainly explained by the much improved performance of scintigraphy after administration of therapeutic doses of 131I. In the majority of patients, especially those whose 131I uptake was limited to the thyroid bed, further scans were negative. Therefore, in these cases, negative Tg values can generally be considered an early indication of satisfactory evolution. However, in 8.5% of all cases, very low Tg levels were associated with metastases. Thus the follow up of thyroid cancer should not rely only upon Tg determination, even after suppression therapy withdrawal.

Lung ventilation and perfusion scintigraphy in the follow up of repaired congenital diaphragmatic hernia.

To evaluate the effects of congenital diaphragmatic hernia (CDH) and pulmonary hypoplasia on subsequent lung function and development, we performed lung 133Xe ventilation and 99mTc perfusion scintigraphies in a group of infants who had undergone surgical repair of a severe left CDH with respiratory distress within the first 6 h of life. The initial lung scans performed in 15 children, 2-3 months of age, demonstrated a decreased ventilation in 7. In 9 children there was a trapping of 133Xe at the left lung base. Perfusion to the hernia side was reduced in 8 of the children. We re-evaluated 11 of these 15 patients after 1-2 years. The ventilation to the left lung was still decreased in 3, but perfusion remained decreased in 9. After 5 years, ventilation to the hernia side was normal in 4 of the 5 patients studied, whereas pulmonary blood flow was abnormal in 4. These results show a progressive improvement of ventilation with a persisting reduction of perfusion to the lung of the hernia side, suggesting a primary vascular pulmonary hypoplasia in CDH.

Thallium-201 imaging in the follow-up of differentiated thyroid carcinoma.

Since thallium-201 imaging has been reported as a potential means of follow-up of patients with differentiated thyroid carcinoma (DTC) during ongoing thyroid suppression therapy, the authors evaluated the diagnostic sensitivity of this procedure in 31 patients known to have metastases or local recurrence. Among 51 tumor sites 201TI imaging had a detection rate of 45% whereas 84% was noted for imaging with 131I administered in therapeutic doses. Thus, even though the effectiveness of the two radionuclides is not strictly comparable due to the difference in the administered doses, Thallium imaging cannot be recommended as the only modality for the follow-up of patients with DTC. Six of the eight tumor sites negative with 131I were positive with 201TI (especially metastatic cervico-mediastinal lymph nodes). So 201TI imaging may particularly be helpful in localizing metastases or recurrences in patients with a negative 131I scan and abnormal levels of serum thyroglobulin.

[Treatment of malignant pheochromocytoma by 131-I-metaiodobenzylguanidine]. / Le traitement des phéochromocytomes malins par la 131-I-métaiodobenzylguanidine.

Twelve patients (2 with only bone metastases, 3 with only soft tissues metastases and 7 with bone and soft tissues metastases) were treated with 131-I-MIBG (specific activity: 20 mCi/mg), 100 to 200 mCi every 3-6 months. A dosimetric study was carried out before each administration. The follow-up ranged from 6 to 24 months and the number of doses ranged from 1 to 8, with 1.85-9 GBq per administration and a cumulative activity of 1.85-62. 2 GBq according to patients. The cumulative absorbed activity ranged from 850 to 9700 cGy. The following side effects were observed: a bone marrow hypoplasia (1 patient) and a transient increase in catecholamines (3 patients). The treatment was successful in 7 patients (3 with soft tissue metastases, 3 with bone and soft tissue metastases and one with bone metastases). This success consisted in clinical improvement and a decrease greater than 50% of hormonal values in the 7 patients and a decrease greater than 50% of tumoral masses in only 3 patients. No complete remission was obtained at this stage of the study. The disease recurred in 1 patient after a year of partial remission. There was no clear-cut relation between the number of doses and the results. This study shows that 131-I-MIBG can give encouraging though limited results.

Detection of anomalous systemic venous return and intraatrial baffle leakage by radionuclide angiocardiography.

The case presented here is a 27-year-old patient who was born with common atrium and left superior vena cava (LSVC). Construction of interatrial septum and intraatrial baffle with pericardium was performed 16 years ago. Radionuclide angiocardiography (RAC) showed that a substantial amount of blood flow from the LSVC was directed to the inferior vena cava through the hemiazygos vein (HAV). It also detected a baffle leak and a left to right shunt at the atrial level. Subsequent RAC after reoperation initially showed insignificant flow through the atrial baffle, major flow through the HAV, and no shunt. Repeat RAC one year after surgery showed increased flow through the baffle and diminished flow through the HAV, without a satisfying explanation. This case illustrates the value of RAC in detecting various types of cardiovascular abnormality and subtle hemodynamic changes.

Topographic and dynamic radioisotopic investigations of interactions between biomaterials and blood components.

Functional investigations using radionuclides to study protein adsorption and platelet adhesion onto biomaterials are described. The authors' novel methods use radiotracers with a dynamic technique. This allows direct observation of the interaction between blood, or simpler biological substances, and artificial materials. Several radiotracers were used in this study, including 111In-platelets, 123I-fibrinogen, 123I-antithrombin III, and 99mTc-tagged red blood cells. The detectors employed were a semiconductor diode or gamma-camera equipped with special collimators. The acquisition and treatment of data were performed with an original device. These methods allowed precise comparisons, especially between platelet adhesion upon different materials in the form of tubes and also protein adsorption and desorption. The results are discussed in terms of materials to be used for work in vivo.

Unsuccessful lung scan due to major right-to-left shunt through a sinus venosus septal defect.

In a patient with a prior history of cerebral abscess and cerebral ischemia, an unsuccessful perfusion lung scan led to a radionuclide angiocardiogram using an arm vein injection. This showed a total right-to-left (R-L) shunt from the superior vena cava (SVC) to the left atrium. Repeat radionuclide study, through a leg vein, demonstrated a moderate R-L shunt and an interpretable lung scan could be obtained. Catheterization and contrast cineangiogram did not provide the exact diagnosis, the preoperative conclusion being anomalous drainage of the SVC into the left atrium, with atrial septal defect (ASD) and partial anomalous pulmonary venous connection to the SVC. The operative diagnosis was high atrial (sinus venosus) septal defect. This example of major but clinically unsuspected R-L shunt emphasizes the value of performing a perfusion lung scan, preferably in conjunction with radionuclide angiocardiography in patients with a prior history of unexplained cerebral abscess or systemic ischemia. Implications of the site of an ASD on quantitation of L-R shunts by radionuclide methods are also discussed.

Single photon emission computed tomography (SPECT), planar scintigraphy, and transmission computed tomography: a comparison of accuracy in diagnosing focal hepatic disease.

A prospective evaluation of conventional planar scintigraphy (PS), single photon emission computed tomography (SPECT), and transmission computed tomography (TCT) was performed in 98 patients with suspected focal hepatic disease (FHD). The three examinations were performed on the same day. TCT had slightly higher sensitivity (91%) and specificity (96%) than either PS or SPECT. The sensitivity and specificity of TCT was also higher than that of the combination of PS and SPECT, which was more accurate than either radionuclide technique alone, with a sensitivity of 85-87% and a specificity of 90%. These differences were not statistically significant. However, receiver operating characteristic (ROC) analysis showed that the performance of TCT was significantly better. The ROC curves also showed, without statistical significance, that SPECT appears to have better diagnostic accuracy than PS and that it seems desirable to complement SPECT imaging with PS views, to reduce the number of equivocal results.

Quantitative analysis of left-ventricular function using gated single photon emission tomography.

We describe a quantitative method that measures segmental motion of the left ventricle, using tomographic slices obtained by gated single photon emission tomography (GSPECT). These slices contain the major axis of the left ventricle and are presumed to show wall motion directed towards a center of contraction. Values of parameters describing segmental wall motion in GSPECT were obtained from 61 patients, who received a left cardiac catheterization 1 hr later. These values were compared with results of similar calculations applied to data from contrast ventriculography. We conclude that GSPECT allows a detailed and quantitative, noninvasive study of wall motion of all left ventricular segments, with high inter- and intraobserver reproducibility.

Radionuclide studies in postoperative evaluation of the Fontan procedure.

Radionuclide studies were performed on 12 patients who had had a Fontan operation for cyanotic congenital heart disease, six of whom had undergone a prior palliative Glenn procedure. The patients without prior Glenn anastomoses were studied by radionuclide first-pass angiocardiography, using a right antecubital vein injection of 99mTc pertechnetate. The patients with Glenn anastomoses required two injections, one by femoral vein to study the Fontan procedure, using bolus injection of 99mTc pertechnetate or microspheres, and the second by right antecubital vein to study the Glenn anastomosis and right lung, using a bolus of microspheres. Gated cardiac blood-pool scintigraphy was used to measure right atrial and left ventricular ejection fraction in three patients. In nine patients, contrast angiography confirmed that these techniques allowed recognition of residual right-to-left shunts, right atrial stasis, right atrial outflow obstructions, left ventricular dysfunction, and right lung arteriovenous fistulas. Noninvasive radionuclide methods seem to be dependable in the postoperative evaluation of patients after the Fontan procedure. First-pass angiocardiography is most helpful in evaluating the dynamics and distribution of blood flow, especially the right atrial output, and gated blood-pool scintigraphy offers a better evaluation of right atrial and left ventricular contraction, so both supply complementary information.

Radionuclide angiocardiography in the diagnosis of congenitally corrected transposition of the great arteries.

Congenitally corrected transposition of the great arteries (CTGA) may constitute a pitfall for interpretation of radionuclide angiocardiography, since the two anatomic discordances cancel each other from a physiologic point of view. However, the unusual shape of the ventricles (due to ventricular discordance) and the relative position of the great arteries (due to transposition) can allow a clear scintigraphic diagnosis, especially for CTGA with mild or absent associated congenital anomalies. Five cases are described. Gated cardiac blood pool imaging is particularly helpful since it permits multiple views, allowing a more detailed study of the scintigraphic signs.

Intraperitoneal injection of technetium-99m sulfur colloid in visualization of a peritoneo-vaginalis connection.

Ten minutes after an intraperitoneal infusion of Tc-99m sulfur colloid, a gamma camera was used to obtain anterior abdominal views. This visualized a peritoneoscrotal communication in an 80-yr-old patient. He had developed extensive edema of the genitals and lower limbs after about 6 wk of continuous ambulatory peritoneal dialysis. At operation the communication was confirmed and closed. A repeat test verified the success of operation.

Cerebrospinal shunt flow in adults: radionuclide quantitation with emphasis on patient position.

Radionuclide quantitation of cerebrospinal fluid (CSF) flow through a ventricular shunt using a Cordis-Hakim valve was performed in 78 adults (138 studies). All remained supine for at least two hours before the study to avoid possible depletion of ventricular CSF. The absolute flow rate distinguished shunt adequacy from patency by defining flow of less than 0.1 ml/min. as abnormal. Measurements were performed with the patient first supine and then erect. When abnormal supine flow was the criterion of malfunction, all obstructions were detected but there were 6 false positives. When abnormal erect flow was considered, there were 5 false negatives. Abnormal flow in both supine and erect positions is a reliable indication of malfunction. The authors conclude that this technique is valuable for neurosurgical management of ventricular shunts.

Radionuclide angiographic demonstration of systemic lung arterialization with arteriovenous fistulas.

Radionuclide angiography has diagnosed systemic arterialization of the right lung base in a patient presenting with a basal thoracic bruit. The bruit was due to high flow in the systemic artery and development of arteriovenous fistulas, confirmed by TCT scan and contrast aortography. But the parenchyma of the right lung base appeared normally aerated on the radiographic studies, and Xe-133 ventilation scintigraphy was normal. This case was therefore classified as systemic arterialization of lung without sequestration.

Deconvolution analysis of radionuclide angiocardiography curves: problems arising from fragmented bolus injections.

Deconvolution analysis of radionuclide angiocardiography time-activity curves (TAC) in the cases of fragmented bolus injections was studied by using a new deconvolution technique based on the maximum a posteriori estimator. This method was first tested by simulation studies which showed its capability for accurate handling of deconvolution both for single and double peak input functions. These simulations have proved this technique to have advantages over a Fourier transform division method used with a low-pass filter. In patient studies, deconvolution of pulmonary TAC by superior vena caval TAC produced poor results in double peak (fragmented) bolus injections, compared with single peak bolus injections (SPBI). This discrepancy seems to be due to the fact that the postulates of linearity and invariance, on which deconvolution analysis is based, do not hold for the 'cardiopulmonary system' which extends from the superior vena cava to the lung. The differences between the model and the real system appear unimportant for SPBI. However, differences become apparent for fragmented bolus injections. Deconvolution analysis should be avoided with this type of input function in this cardiopulmonary system.

Transient intense gastric fixation of 99mTc-MDP.

A case is described of reversible, intense gastric uptake of 99mTc-MDP in the fundal region of a patient with myeloma, while very little transient pulmonary fixation was seen. The significance of this unusual finding in terms of relevant blood chemistry, results of gastric biopsies, which failed to show metastatic calcification, and the drugs administered is discussed.