Iodine-131 metaiodobenzylguanidine (I-131 MIBG) diagnosis and therapy of pheochromocytoma and paraganglioma: current problems, critical issues and presentation of a sample case.

Iodine-131 metaiodobenzylguanidine (I-131 MIBG) has been used for the diagnosis and treatment of malignant pheochromocytomas (PHEO) and paragangliomas (PGL) since 1980's. Despite increasing amount of experience with iodine-131 (I-131) MIBG therapy, many important questions still exist. In this article, we will discuss the current problems learned from clinical experience in diagnosis and therapy of PHEO/PGL with I-131 MIBG, and present a sample case to emphasize the critical aspects for an optimal treatment strategy.

Malignant pheochromocytoma and paraganglioma: future considerations for therapy.

Pheochromocytoma and paraganglioma are rare neuroendocrine tumors. Knowledge about such neoplasms ameliorated in the last 10-15 years with the discovery of increasing number of germ line mutations even in apparently sporadic cases. Seemingly, genetic tests are going to be an integral part of diagnostic procedures. Standard therapies (advanced surgery, radiometabolic therapy, chemotherapy and radiotherapy) have revealed suboptimal results in tumor size reduction and survival. Currently, there is no standard therapeutic protocol and thus some patients end up with overtreatment while others are undertreated. An effective molecular target therapy aiming at permanent control of these highly complex neoplasms should be the aim of future efforts. In clinical setting investigatory trials with multiple drug therapies targeting a variety of different parallel pathways should be available. Successful management requires a multidisciplinary teamwork.

Gallium-68 DOTANOC imaging in paraganglioma/pheochromocytoma: presentation of sample cases and review of the literature.

Gallium-68 DOTANOC is a high affinity somatostatin receptor ligand, first introduced in 2005 for imaging neuroendocrine tumors. Due to its technically simple production, broad availability, favourable biodistribution and advantageous dosimetry, although not approved yet in all European countries, gallium-68 DOTANOC has rapidly gained acceptance in the diagnostic and therapeutic work-flow of different types of neuroendocrine tumors. Principal indications in clinical practice in countries where it is officially approved include diagnosis and staging, restaging after treatment, identification of sites of unknown primary and selection of patients with neuroendocrine tumors eligible for therapy with somatostatin analogues.

The role of nuclear medicine in the diagnosis of cancer of unknown origin.

Cancer of unknown origin (CUO) is defined by the absence of any primary tumour in biopsy-proved metastatic cancer. CUO accounts for a 5-10% of all malignancies. These tumors have a specific biology with clinical characteristics of rapid progression and atypical metastases. Diagnostic evaluation is directed at the identification of treatable subset. Accurate diagnostic workup is crucial because both prognosis and survival rates depend mainly on detection of the primary tumor site. Although these patients undergo extensive imaging procedures, nuclear medicine techniques are under-utilized despite their ability of providing molecular information. Positron emission tomography has an emerging role in this clinical challenge along with other nuclear medicine methods including, bone scan, thyroid scintigraphy.

Thallium-201 imaging in the assessment of tumor response to anti-tumor treatments.

The advantages and limitations of (201)Tl imaging in assessing the tumor response to anti-cancer therapy are discussed in this review. (201)Tl has distinctive advantages but more recent agents such as (99m)Tc MIBI and positron emitters have some clinical superiorities over (201)Tl in this usage.

Detection of cold bone metastasis by Tc-99m MIBI imaging.

We present a case of renal cell carcinoma metastasis to the skull, appearing as a photopenic area on Tc-99m MDP bone scan and with focal uptake in the same region on Tc-99m MIBI imaging.

Diagnosis of complete ectopic lingual thyroid with Tc-99m pertechnetate scintigraphy.

The authors present four cases of ectopic lingual thyroid disease diagnosed by Tc-99m pertechnetate scanning, which is an efficient diagnostic tool that yields high-quality images in this clinical setting.

Effect of the Valsalva manoeuver on diastolic filling indices in patients with essential hypertension.

In some hypertensive patients, echocardiographic examination does not reveal any pathologic finding in spite of a documented blood pressure elevation. In our study, we investigated the effect of preload reduction with Valsalva manoeuver on transmitral flow velocities in hypertensive patients with normal mitral flow pattern and compared the results with a healthy control group. Sixty-eight patients without evidence of coronary artery disease or heart failure (28 female, 40 male, age 50 +/- 7) were divided in two groups according to their E/A ratio as those with diastolic dysfunction (n = 36) and without diastolic dysfunction (DD(-): n = 32). DD(-) patients and the control group (n = 20) performed Valsalva manoeuver and their pulsed-Doppler mitral flow measurements were repeated at the strain phase. During Valsalva manoeuver, E wave velocity decreased in all subjects. In the controls, peak A velocity showed a similar decline and E/A ratio remained over 1.0. However, in 72% of DD(-) patients A velocity did not change or increased and their E/A ratio fell below 1.0. In 47% of the patients with an E/A ratio reversal after Valsalva manoeuver, myocardial perfusion scintigraphy revealed reversible defects whereas none of the patients whose E/A ratio remained over 1.0 had perfusion defects. It is concluded that: (1) in hypertensive patients with normal E/A ratio Valsalva manoeuver should be performed in order to unmask a probable false normal finding, (2) an important percent of hypertensive individuals have left ventricular relaxation abnormalities, and (3) diastolic dysfunction develops together with a decrease in coronary reserve.

Tc-99m MIBI imaging in malignant fibrous histiocytoma.

The authors report a case of malignant fibrous histiocytoma of the left forearm demonstrated by Tc-99m MIBI imaging. The tumor originated in the soft tissue of the forearm; no obvious bone invasion or metastasis was detected scintigraphically or radiologically.

Better visualization of retinoblastoma metastases with Tc-99m sestamibi versus Tl-201.

Tc-99m sestamibi has been shown to accumulate in several primary malignant tumors, but data regarding its use in the detection of distant metastases are limited. Despite its physical limitations, Tl-201 now has a definite place in the routine evaluation of certain primary and metastatic tumors. This report describes the value of Tc-99m sestamibi and its superiority to Tl-201 in the visualization of distant metastases in a 2-year-old girl with bilateral retinoblastoma. Three sites of soft tissue and bone metastasis were demonstrated by Tc-99m sestamibi imaging. Of these metastases, the one in the parieto-occipital region showed evident Tl-201 uptake, while the other two in the right arm and chest wall showed only slightly increased uptake, which could hardly be spotted without the confirmation of a later Tc-99m sestamibi scan. The scintigraphic findings were confirmed with histopathologic examination. Tc-99m sestamibi scan is effective and superior to Tl-201 in the detection of distant soft tissue and bone metastases from retinoblastoma.

Technetium-99m and indium-111 double labelling of granulocytes for kinetic and clinical studies.

A new technique of labelling granulocytes with both technetium-99m hexamethylpropylene amine oxime (HMPAO) and indium-111 in a single protocol was developed in order to exploit the advantages of each radiolabel in clinical and investigative studies. Fourteen patients were included in this prospective study. Granulocytes were labelled with both 111In-tropolonate and 99mTc-HMPAO. In vitro shape change assay and in vivo distribution and recovery studies were performed to assess the activation of and damage to these cells due to the labelling procedure. The comparative kinetics of 111In and 99mTc in the blood, liver, spleen, and bone marrow were studied by blood sampling and dual radionuclide imaging early (1 h) and late (24 h) after injection. The functional integrity of the double-labelled granulocytes and the feasibility of the technique were investigated in 14 patients with a painful prosthetic hip due to causes other than infection. The efficiency of double labelling was 63% (SD 14%) for 111In and 39% (SD 12%) for 99mTc-HMPAO. In vitro granulocyte activation and ex vivo recovery values were comparable to those from single radionuclide labelling. No artefactual granulocyte sequestration was seen in the lungs or liver. The radioactivity was distributed between the liver, spleen and bone marrow and, to a lesser extent, the lung. Early 99mTc counts in the liver, spleen and bone marrow, in relation to background, were significantly higher than 111In counts while the reverse was seen in late images.(ABSTRACT TRUNCATED AT 250 WORDS)

Granulocyte margination in bone marrow: comparison with margination in the spleen and liver.

The kinetics of radiolabelled granulocytes in the reticuloendothelial system were studied in order to evaluate granulocyte margination in bone marrow. A total of 34 patients took part in a two-part study. In the first part, bone marrow uptake of indium-111-labelled granulocytes was retrospectively analysed in early (3-h) and late (24-h) images in 26 patients, 13 with bronchiectasis and 13 with enclosed abdominal abscesses. The ratios between early and late counts from the bone marrow, spleen, liver and inflammatory lesion were used to quantify granulocyte margination in bone marrow, postulating that if the lesion to bone marrow ratio at 24 h exceeds the value at 3 h, then the "excess" bone marrow counts on the early images would represent margination. In the second part, this suggestion was prospectively tested using Rutland-Patlak graphical and deconvolution analysis of dynamic data, acquired in 8 patients undergoing routine scanning with technetium-99m HMPAO-labelled granulocytes. In the first part of the study, it appeared that the bone marrow is a regional site of granulocyte margination, like the spleen, with at least one-half of the 3-h marrow signal arising from marginated granulocytes, compared with about two-thirds from the spleen. In the second part, it was found that the gradient of the Patlak plot, based on spleen and marrow, continuously decreased, consistent with bi-directional movement of cells between these organs and the blood. Granulocyte pooling in the marrow was confirmed with deconvolution analysis, which generated biphasic retention functions for marrow and spleen. These curves were also consistent with two-way granulocyte exchange, and gave mean cell transit times in both organs of about 12 min and probabilities of extraction on each pass of 5-10%. We conclude that granulocytes marginate in bone marrow to an extent similar to that in the spleen.

Tc-99m MIBI uptake in pulmonary sarcoidosis. Preliminary clinical results and comparison with Ga-67.

During tumor imaging research, the authors incidentally discovered that Tc-99m MIBI is taken up by pulmonary sarcoidosis. In order to evaluate this uptake, they performed Tc-99m MIBI planar and SPECT imaging in 7 patients and compared it with Ga-67. Six out of 7 patients showed evident uptake of Tc-99m MIBI in enlarged hilar lymph nodes. One of the patients, who had been on corticosteroid treatment, showed only faint uptake (negative result), in whom Ga-67 uptake was seen in hilar lymph nodes although it was less evident than the uptake in the other patients. The lymph nodes were better demonstrated with Tc-99m MIBI. The fact that enlarged hilar lymph nodes in a patient on corticosteroid treatment showed faint uptake suggests that Tc-99m MIBI could be helpful for assessing the response to treatment. The preliminary experience in a limited number of patients showed that Tc-99m MIBI is taken up by pulmonary sarcoidosis and it appears to be a potential alternative to Ga-67. Further study is necessary to evaluate its ultimate role in pulmonary sarcoidosis imaging.