Non-131I-scintigraphy in the treatment and follow-up of thyroid cancer. Single-photon-emitters or FDG-PET?

With respect to further therapeutic options, whole-body 131I scintigraphy (WBS) is the most important functional imaging technique during treatment and follow-up of differentiated thyroid cancer. But in many patients, thyroid cancer tissue does not concentrate 131I and can therefore not be localized using WBS. In addition to morphologic techniques, which have a low specificity in many cases, other methods are necessary to localize tumor tissue in these patients. Besides 201Tl, which has been used initially as a tumor-seeking agent, sestamibi, tetrofosmin and 18F-DG for PET imaging have been evaluated in differentiated thyroid carcinoma. This paper summarizes the clinical impact of functional imaging with tracers besides 131I. In direct comparison, 18F-DG-PET has the highest sensitivity, which exceeds 80% in cases with negative WBS. If available, this method should be considered in all patients suffering from differentiated thyroid cancer with suspected recurrence and/or metastases, particularly in cases with elevated thyroglobulin values and negative WBS. But also 99mTc-labeled tracers can be used to detect tumor tissue with a sufficient sensitivity. In medullary thyroid cancer, which presents frequently with diagnostic difficulties, 111In-octreotide, 99mTc-(V)-DMSA, 131I/123I-mIBG, and anti-CEA can be used, in addition.

[Imaging of secondary pulmonary changes in central bronchial carcinomas by F-18-FDG PET]. / Darstellung sekundärer pulmonaler Veränderungen bei zentralen Bronchialkarzinomen in der F-18-FDG-PET.

AIM: The presented study was performed in order to evaluate the potential interference of secondary pulmonary changes (dystelectasis, retention pneumonia) with bronchial carcinomas in F-18-FDG-PET. METHOD: A retrospective analysis of F-18-FDG-findings in 33 patients with bronchial carcinoma (staging) was performed. Seven out of fourteen patients with central tumor localisation had secondary pulmonary changes (thorax-x-ray, CT), which were classified as dystelectasis or atelectasis in five cases and as retention pneumonia in two cases. RESULTS: Whereas dystelectasis and atelectasis without clinical signs of infection showed only mild to moderate FDG-accumulation (SUV 1.0-2.5; mean: 1.74), an intense FDG-uptake in the two cases with retention pneumonia (SUV 8.4 and 5.5) was observed. Despite of the typical wedge-like shape of pneumonia, differentiation between bronchial carcinoma and pneumonia can be a problem. CONCLUSION: We suggest, that an antibiotic treatment in patients with known retention pneumonia should be performed prior to the PET-scan in order to reduce the interference of inflammatory changes.

[123I]IBZM SPECT for imaging of striatal D2 dopamine receptors in 56 schizophrenic patients taking various neuroleptics.

OBJECTIVE: The purpose of this study was to compare the binding of various typical and atypical neuroleptics to striatal D2 dopamine receptors in schizophrenic patients. METHOD: Fifty-six inpatients with schizophrenia, including 14 with schizoaffective disorder and one with schizophreniform disorder, were evaluated. Fourteen patients were neuroleptic free. Single photon emission computed tomography (SPECT) was performed 90 minutes after intravenous injection of [123I]benzamide ([123I]IBZM). Subsequent semiquantitative analysis of D2 receptor binding was done with the use of the basal ganglia (striatum)/frontal cortex (BG/FC) ratio of activity. Clinical symptoms were rated with the Positive and Negative Syndrome Scale and the Hamilton Depression Rating Scale. RESULTS: The BG/FC ratios in patients taking typical neuroleptics were significantly lower than those in the neuroleptic-free subjects but not lower than those in the patients taking atypical neuroleptics (clozapine, remoxipride). For atypical antipsychotics, a dose-dependent relationship with striatal D2 receptor binding could not be demonstrated. BG/FC ratios were not significantly correlated with clinical symptoms or with duration of illness. CONCLUSIONS: The results indicate that [123I]IBZM SPECT is useful for semiquantitative imaging of striatal D2 dopamine receptors and for estimating their blockade by neuroleptics. Thus, it may improve drug monitoring in psychiatric patients. Furthermore, the findings suggest a complex relationship between the antipsychotic effect of atypical neuroleptics and D2 receptor blockade.

[Immunoscintigraphic detection of metastasis in malignant melanoma in the head and neck area]. / Immunszintigraphischer Metastasennachweis bei malignen Melanomen im Kopf-Hals-Bereich.

The value of immunoscintigraphy in patients with metastatic malignant melanoma of the head and neck is compared with clinical, radiological and histological findings. 25 immunoscintigraphic examinations in 16 patients were evaluated. Scintigraphy was performed during primary and follow-up diagnosis of head and neck melanoma of the skin (n = 8), nose and sinuses (n = 3), petrosal bone (n = 1) and sclera (n = 1) as well as in cervical lymph node metastases of distant melanoma (n = 2) and melanoma of an unknown primary tumour (n = 1). Immunoscintigraphy was performed with 99mTc-radiolabelled melanoma specific antibodies against a melanoma-associated cell membrane-bound antigen (glycopolypeptide). The sensitivity of the method was 88%, specificity was 80%. The prior significance of immunoscintigraphy is based on the detection of occult cervical lymph node metastases not detectable by means of palpation and radiography. Pulmonary and liver manifestations could not be safely identified due to the physiological enhanced blood pool in these organs. The results obtained indicate that immunoscintigraphy may yield more information about the status of pathologically altered tissue and in certain cases may influence the therapeutic procedure.

Planar and SPECT imaging with technetium-99m labeled antigranulocyte antibodies in bone and soft tissue infection.

Scintigraphy with technetium-99m labeled antigranulocyte antibodies including planar and SPECT imaging demonstrated areas of inflammation in bone and soft tissue of the thigh of a 38-year-old man who had a fracture of the femur 20 years earlier. The clinical potential of this imaging modality in the diagnostic assessment of inflammatory diseases is discussed.

Tc-99m labeled monoclonal antibodies against granulocytes (BW 250/183) in the detection of appendicitis.

Scintigraphy with Tc-99m labeled antigranulocyte antibodies (BW 250/183 MoABs) was performed in 32 patients with suspected appendicitis. Abdominal imaging (planar/SPECT) was performed 2 hours after injection of the tracer. All patients also had surgery and a histologic examination of the resected tissue. Of the patients, 17 suffered from "acute appendicitis" and 12 had right positive scans (sensitivity = 70.6%). In 15 patients, acute appendicitis could have been ruled out, and in 11 of these cases the scan was true negative (specificity = 73.3%). The overall accuracy was 71.8% (23/32 cases). The use of Tc-99m antigranulocyte MoABs may overcome the problems associated with the Tc-99m HMPAO granulocyte and In-111 oxine approaches, which include nonspecific intestinal activity or the lack of timeliness. The use of Tc-99m labeled antigranulocyte antibodies is suitable as an emergency procedure and may play a role in the management of patients with suspected appendicitis.

[Diagnostic evaluation of acute scrotum--testicular perfusion scintigraphy]. / Abklärung des akuten Skrotums--Hodenperfusionsszintigraphie.

The method of and the results obtained with testicular scintigraphy in the differential diagnosis of acute scrotal pain are described. Both sensitivity and specificity were found to be high and in excess of 90%. Misinterpretation of findings is rare and is seldom reported except in case reports. Normal findings usually genuinely reflect absence of disease, and only in the case of suboptimal imaging conditions they might correspond to a false-negative finding in the presence of acute torsion. Chronic torsion may be missed on scintigraphy because of intermediate normalization of arterial perfusion at the time of the investigation. Missed torsion presents a characteristic activity pattern. The halo sign is a proven sign of avitality of the testicle. Orchitis and epididymitis are correlated with hyperperfusion and hyperaemia and are reliably diagnosed by scanning. When testicular scintigraphy is needed immediate availability is essential. In a nuclear medicine department with standard equipment, the investigation can be started within 5 min; it takes about 15 min to perform and the findings can be evaluated within another 5 min. Acute testicular torsion that has already been reliably diagnosed by clinical examination is not an indication for testicular perfusion scintigraphy. This diagnostic procedure is, however, valuable if the clinical findings are equivocal and, especially, if a conservative treatment is planned.

[Current aspects of the pathology, diagnosis and therapy of C-cell carcinoma. A symposium held in Bonn, July 1991]. / Aktuelles zur Pathologie, Diagnostik und Therapie des C-Zell-Karzinoms. Symposium in Bonn im Juli 1991.

An essential element in the histological differentiation of medullary thyroid cancer (MTC) from other thyroid tumors is the use of immunohistochemical methods. The detection of calcitonin in the tumor cells is decisive. Factors which impair the prognosis of MTC are age (> 40 y), male sex, elevated DNA-content and mitotic activity of the tumor cells, immunoreactivity against dopa decarboxylase, histaminase and Leu-M1-antigen. Family screening is based mainly on calcitonin-stimulation tests (using pentagastrin or calcium) as a genetic marker for routine screening is not available yet. Scintigraphic methods using 99mTc-(V)-DMSA, 201Tl-chloride or 99mTc-anti-CEA antibodies become more important, especially in the detection of recurrent disease. Selective venous blood sampling is another sensitive method for localizing recurrent disease. Surgical treatment plays the dominant role in the management of MTC. Complete thyroidectomy in conjunction with systematic lymphadenectomy is now the primary treatment of choice.

The role of nuclear medicine in oncology.

Nuclear Medicine offers screening methods for oncology such as bone and bone marrow scintigraphy. During the last two decades, special procedures have gained widespread application. This paper is centered around the "tumor-specific" radiopharmaceuticals. In patients with thyroid cancer, I-131 still plays a significant role. Ga-67 still has its indications in lymphoma, while in other diseases Tl-201 chloride is now the agent of choice. Especially in thyroid cancer, Tl-201 has proved to be a reliable tumor imaging radiopharmaceutical. More recently, Tc-99m MIBI was introduced for tumor imaging. Tc-99m HMPAO may also be used for tumor scintigraphy, especially in brain lesions. In addition, I-123 IMP has successfully been used for imaging malignant melanoma. Another promising field of tumor diagnosis is receptor imaging. In neuroblastoma and malignant pheochromocytoma, I-131/123 mIBG is the radiopharmaceutical of choice and may be considered as a receptor imaging agent also. First clinical results with In-111 octreotide show potentials as somatostatin-receptor radiopharmaceutical in insulinoma, islet cell carcinoma, medullary and lung cancer, while I-123 estradiol needs some improvement until it may be recommended as diagnostic tool in breast cancer. Since 1978, radiolabeled poly- or monoclonal tumor antibodies and their fragments have gained widespread application. Especially the Tc-99m 225.28S melanoma antibody, I-131 or Tc-99m CEA and In-111/I-131 labeled OC-125 antibodies have proven to be of clinical significance in melanoma, colorectal and ovarian cancer.

Technetium-99m-labeled anti-granulocyte antibodies in suspected bone infections.

The introduction of 99mTc-labeled anti-granulocyte antibodies seemed to provide advantages in comparison with formerly used in vitro methods to label autologous white blood cells for inflammation imaging. For this reason, we have undertaken a study to evaluate the clinical significance of this method. Thirty unselected patients with suspected bone infections were studied prospectively using the monoclonal 99mTc-labeled anti-granulocyte antibody. Twenty patients were referred with suspected infections of the peripheral bones (Group I), as well as 10 patients with suspected infections of the spine (Group II). Planar whole-body scans were performed 4 hr and 20 to 24 hr after administration of 500 MBq of the labeled antibody. Scans were considered positive for a bacterial (septic) infection when a focally increased antibody accumulation occurred. All scans were evaluated in blinded fashion by two experienced readers. Of the 20 studies from Group I patients, four false-positive scintigraphic findings were observed, and one false-negative, resulting in a specificity of only 64% and a sensitivity of 89%. In Group II (10 studies), five scans were true-negative, and five false-negative. For both groups, the specificity of the scintigraphic method was quite low (75%), and the sensitivity was also relatively low (57%). The results of this study demonstrate that in an unselected patient population in whom the diagnosis is not known, scintigraphy with 99mTc-anti-granulocyte antibodies is not a reliable method for detecting septic inflammatory lesions: In addition, use of this method excludes septic lesions with only a moderate likelihood (83% negative predictive value).

[99mTc-anti-granulocyte antibodies (BW 250/183) in the detection of appendicitis]. / 99mTc-Anti-Granulozyten-Antikörper (BW 250/183) zum Nachweis der Appendizitis.

Scintigraphy with 99mTc-labeled anti-granulocyte antibodies (AGAb) was performed in 50 patients with suspected appendicitis. Sequential and static imaging as well as SPECT of the pelvis and abdomen was performed 2 h p.i. In all patients the diagnosis was confirmed either histologically or by long-term follow-up. 13 patients had histologically proven acute appendicitis. In 11 patients the appendix scan had been positive and in 2 patients the scan had shown no significant tracer uptake in the right lower abdomen. The remaining 37 patients turned out not to have acute appendicitis. 29 out of these patients had negative and 3 had positive scan findings. In 5 patients the scan was equivocal. Out of these patients 2 had pathologic findings on the left side of the abdomen which turned out to be acute diverticulitis in one patient and acute peritonitis in the other. The remaining 3 patients with unclear scintigraphic findings had no acute appendicitis. Scintigraphy with AGAb is fast and easy to perform and thus superior to cell labeling methods for diagnosing acute appendicitis. Sensitivity for the diagnosis of acute appendicitis was 85% with a specificity of 91%. Chronic or scarred non-granulocytic appendicitis--in which there is often no definite indication for surgery--was negative in our study except for two cases.

[A comparison of 201Tl and 99mTc-MIBI in the follow-up of differentiated thyroid carcinomas]. / Vergleich von 201Tl und 99mTc-MIBI in der Nachsorge des differenzierten Schilddrüsenkarzinoms.

12 patients with suspected recurrence of differentiated thyroid carcinoma following thyroidectomy, radioiodine therapy and, in some cases, external radiation therapy had 201Tl and 99mTc-MIBI scintigraphy. Except in one case, the findings concerning tumor localization and extension were identical. In all cases, locoregional lymph node metastases as well as osseous metastases were imaged by 201Tl and 99mTc-MIBI scintigraphy. MRI images obtained in all patients with suspected lymph node metastases revealed inoperable situations in 2 cases, whereas there was no correlation in 1 patient with positive 201Tl and 99mTc-MIBI scintigraphy. In contrast, the sensitivity of the two methods was relatively low in the detection of pulmonary metastases which were imaged in 1 out of 3 patients only. Discrepancies between 201Tl and 99mTc-MIBI were observed in a case of axillary lymph node metastasis. Although tumor-/background ratios were slightly higher for 201Tl, 99mTc-MIBI SPECT showed a higher imaging quality compared to 201Tl SPECT, especially in deeply situated tumor lesions. In conclusion, 99mTc-MIBI seems to be a promising alternative imaging agent in the follow-up of differentiated thyroid carcinomas.

[Tumor scintigraphy using 123I-labeled estradiol in breast cancer--receptor scintigraphy]. / Tumor-Szintigraphie mit 123J-markiertem Ostradiol beim Mammakarzinom--Rezeptorszintigraphie.

The estrogen receptor (ER) status is an important factor for prognosis and endocrine therapy of breast cancer. Therefore 16-alpha-123I-iodoestradiol-17-beta (123I-E2) as a receptor-specific radiopharmacon was used for scintigraphic tumor detection in 62 patients suspected of breast cancer. The studies were performed as a multicenter trial (5 university hospitals) to validate the method and to overcome methodical problems. A fast tracer elimination from the blood pool into the liver was seen, followed by biliary excretion allowing early imaging of the thorax due to low background activity but resulting in difficult imaging conditions of the abdomen. In 42 patients (30 carcinomas, 12 benign lesions) the overall sensitivity was 66% (ER status cut-off: 10 fmol/mg). Some patients with breast cancer showed focal or diffuse uptake in the area of primary lymph drainage (parasternal, axillary) without any clinical correlation, demanding follow-up investigations. There was only one false-positive result in a receptor-negative primary carcinoma; thus, the non-invasive determination of the ER status seems to be feasible. The sensitivity of 123I-E2 in the detection of primary breast cancer or metastases and recurrences is low compared to mammography and other methods; therefore, 123I-E2 scintigraphy cannot be used as a screening method. Differentiation of malignant and benign tissue is even more difficult as both may have a positive ER status, for example in mastopathy. Nevertheless, 123I-E2 scintigraphy is an in vivo imaging technique for the detection of breast cancer depending on the ER status and provides information about tumor localisation. It may become a specific method for the non-invasive diagnosis of the ER status and may be helpful in follow-up studies. As a receptor-specific agent 123I-E2 may give answers to questions of tumor heterogeneity and changes of the ER status during therapy.

[Increased sensitivity of whole-body scintigraphy with I131 for the detection of iodine-accumulating metastases by means of delayed imaging]. / Erhöhte Sensitivität der Ganzkörperszintigraphie mit 131J für den Nachweis jodspeichernder Metastasen durch spätere Aufnahme-Zeitpunkte.

In the follow-up of thyroid cancer patients we sometimes observed discrepancies between elevated thyroglobulin levels and negative results of posttherapeutic or diagnostic scans 48 h and 72 h after oral application of 131I routinely. Consequently, delayed 131I scans (96 h and later) were performed in addition. In all cases, delayed 131I scans either showed a higher imaging quality or additional metastatic lesions. Thus, posttherapeutic (and diagnostic) scans should include late images (4 d and later).