PET in the diagnostic evaluation of adrenal tumors.

Early experience with positron emission tomography (PET) has provided exciting results in the evaluation of a broad spectrum of neoplasms, to include primary adrenal tumors, their metastases and metastatic disease to the adrenal glands. By virtue of the well-recognized propensity of malignancies to preferentially use glycolysis as an important energy source and the stimulation of mechanisms designed to absorb substrate glucose, the glucose analog, [18F]fluorodeoxyglucose, has become a successful radiopharmaceutical in the scintigraphic evaluation of adrenal tumors. Building upon prior experience gained with imaging the adrenal gland, other positron-labeled radiopharmaceuticals are finding their way into clinical use. The 11b-hydroxylase inhibitor, metomidate labeled with 11C has been used to scintigraphically identify tissues of adrenocortical origin, to accurately identify recurrent and metastatic adrenocortical carcinoma and may be useful in assessing the malignant potential of these tumors and predicting survival in afflicted patients. Adrenomedulla imaging with 11C- and 18F-labeled catecholamines and catecholamine analogs draws heavily from the experience gained from predecessor compounds, labeled with single photon emitting isotopes and, in some instances, single photon emission tomography, and has been shown to depict with high efficacy pheochromocytomas, neuroblastomas and other neoplasms of neural crest origin. Additional structural and functional information provided by computed tomography (CT), performed as part of hybrid PET/CT imaging directly complements PET and adds measurable diagnostic value in the evaluation of adrenal tumors.

Controversies in diagnostic approaches to the indeterminate follicular thyroid nodule.

In this paper we review the controversies in diagnostic approaches to follicular thyroid nodules with indeterminate cytology. The authors consider some of the controversies surrounding the indeterminate follicular thyroid nodule, including the definition and the postoperative outcome. Among the techniques that may improve preoperative diagnostic accuracy are large needle aspiration biopsy and immunohistochemistry for galectin-3.

Controversies on minimally invasive procedures for radio-guided surgery of parathyroid tumours.

The definitive treatment of primary hyperparathyroidism (PHPT) is the surgical approach which traditionally consists of bilateral neck exploration with visualization of at least 4 parathyroid glands and removal of the enlarged ones. However, the most frequent cause of PHPT is a solitary parathyroid adenoma so that a limited neck exploration in order to remove the solitary adenoma alone appears adequate to many surgeons. The recent significant improvements achieved in the pre-operative parathyroid localization techniques, mainly the parathyroid scintigraphy, and the introduction in surgical practice of measurement of quick parathyroid hormone, endoscopic procedures, and intra-operative gamma probes used together specific radiopharmaceuticals allowed to offer the PHPT patient a limited neck exploration as the unilateral neck exploration and the minimally invasive parathyroidectomy. The present article deals with the role of the intra-operative gamma probes used together with specific radio-pharmaceuticals, discussing the principal advantages and disadvantages of each currently used radio-guided approach.

Imaging of human infection with (131)I-labeled recombinant human interleukin-8.

UNLABELLED: The chemotactic cytokine interleukin-8 (IL-8) plays an important role in attraction and activation of polymorphonuclear leukocytes in infection and inflammation. A pilot study was conducted to determine if radiolabeled IL-8 would depict infection in humans. METHODS: Human recombinant IL-8 (rhIL-8) labeled with (131)I (specific activity, 0.4-0.7 MBq [11-18 microCi] (131)I/microg IL-8) was injected intravenously into 8 diabetic patients with active foot infections and evidence of osteomyelitis, 2 patients with successfully treated osteomyelitis, and 1 patient with cellulitis of the thumb. RESULTS: Focal accumulation of (131)I-rhIL-8 was seen in 8 of 8 patients with active foot infection and diffuse uptake was seen in the thumb of the 1 patient with cellulitis. In the 2 patients with successfully treated bone infection, multiphase (99m)Tc-hydroxyethylene diphosphonate bone scans were negative early, but late-phase (>3 h) uptake depicted degenerative lesions that did not image with (131)I-rhIL-8. CONCLUSION: (131)I-rhIL-8 accumulates rapidly within infected foci in osteomyelitis and cellulitis but not in successfully treated infections or degenerative joint disease.

Limbic activation and psychophysiologic responses to aversive visual stimuli. Interaction with cognitive task.

We mapped regional brain activity and peripheral psychophysiologic responses, occurring in response to evocative emotional stimuli, and examined whether task instructions could modulate limbic activation. Ten subjects viewed pictures with neutral or aversive emotional content during simultaneous measurement of peripheral psychophysiology and brain activity with [15O]water positron emission tomography (PET). Cognitive task was manipulated by having the subjects rate the pictures or perform a recognition memory task. Aversive pictures, relative to neutral pictures, increased cerebral activity in bilateral amygdala, thalamic/hypothalamic area, midbrain, and left lateral prefrontal cortex, along with greater skin conductance responses (SCR). Voxel-by-voxel correlation coefficients between regional brain activity and SCR showed significant positive correlation peaks in the thalamus and right amygdala. Limbic activation was significantly greater during the rating condition compared to the recognition condition, suggesting that when task demands modify emotional responses, this modulation can occur at the level of limbic activity.

Artifacts, anatomical and physiological variants, and unrelated diseases that might cause false-positive whole-body 131-I scans in patients with thyroid cancer.

The whole body 131-I scan remains an important component in the postoperative treatment of patients with well-differentiated thyroid cancer. Because normal thyroid tissue remnants and residual or metastatic foci of well-differentiated thyroid cancer have the unique ability to concentrate, organify, and store 131-I, the whole body scan provides a depiction of those tissues that can be ablated with therapeutic doses of 131-I. Over time, it has become obvious that the whole body scan may also reveal foci of 131-i uptake owing to a wide variety of other causes. We provide a detailed pathophysiological classification of the artifacts, anatomic and physiological variants, and nonthyroidal diseases that may give rise to false-positive whole body scans in postoperative patients with thyroid cancer. These include ectopic foci of normal thyroid tissue; nonthyroidal physiological sites (eg, choroid plexus, salivary glands, gastric mucosa, urinary tract); contamination by physiological sections; ectopic gastric mucosa; other gastrointestinal abnormalities; urinary tract abnormalities; mammary abnormalities; serous cavities and cysts; inflammation and infection; nonthyroidal neoplasms; and currently unexplained causes. This article also provides a detailed review of the widely scattered English language literature in which these phenomena were originally described.

Medial frontal cortex involvement in PTSD symptoms: a SPECT study.

The regional cerebral blood flow (rCBF) responses to a combat stress-related auditory stimulus was examined in Vietnam veterans diagnosed with posttraumatic stress disorder (PTSD). Based on prior data in healthy subjects, we hypothesized that the medial prefrontal cortex may be involved in the processing of stress responses. Twelve male veterans diagnosed with PTSD, 11 age-matched, combat-exposed subjects without PTSD, and 12 healthy control subjects were studied with single-photon emission tomography and the blood flow tracer [99mTc]-HMPAO. Subjects were studied twice, while listening to combat sounds or white noise. Significant increases in the blood flow to the medial prefrontal cortex were observed in PTSD patients, but not in the control groups, which correlated at trend levels with psychophysical measures of stress response. These data support the involvement of the medial prefrontal cortex in the pathophysiology of PTSD, possibly mediating some of its symptoms.

Brain activation in PTSD in response to trauma-related stimuli.

BACKGROUND: Repetitive recall of traumatic memories and chronic intermittent hyperarousal are characteristic of posttraumatic stress disorder (PTSD). Hyperarousal and memory dysfunction implicates "limbic" brain regions, including the amygdaloid complex, hippocampal formation, and limbic cortex, such as the orbitofrontal and anterior cingulate areas. To investigate the neurobiologic role of these brain regions in PTSD, we measured regional cerebral blood flow in PTSD with single photon emission computerized tomography (SPECT) during a symptom provocation paradigm. METHODS: Fourteen Vietnam veterans with PTSD, 11 combat control subjects, and 14 normal control subjects were studied with [99mTc]HMPAO in two sessions 48 hours apart: one session after exposure to white noise and the other following exposure to combat sounds. Skin conductance, heart rate, and subjective experience were recorded at the time of the studies. RESULTS: Activation for all three groups occurred in the anterior cingulate/middle prefrontal gyrus. Activation in the region of the left amygdala/nucleus accumbens was found in PTSD patients only. Deactivation was found in all three groups in the left retrosplenial region. CONCLUSIONS: These findings implicate regions of the "limbic" brain, which may mediate the response to aversive stimuli in healthy individuals and in patients suffering from PTSD.

Intracavitary therapy of craniopharyngiomas.

Craniopharyngiomas are benign cystic para-hypophyseal tumors often associated with hypopituitarism and visual-field abnormalities. Their therapy by surgery and external beam radiotherapy is imperfect. The intracavitary instillation of beta-emitting colloid radiopharmaceuticals into the cysts permits the delivery of far higher radiation doses to the cyst lining than is possible by external beam radiotherapy. This technique permits destruction of the lining epithelium with resultant elimination of cyst fluid formation and cyst shrinkage in up to 80% of cases.

Altered radiopharmaceutical distribution in myeloma: bone tracer in the heart and heart tracer in the bone.

Tissue deposits of amyloid may lead to various clinical symptoms and signs, depending on the site of deposition. In addition, a specific subtype of amyloidosis, AL protein type, is associated with multiple myeloma. Two cases representing contrasting examples of altered radiopharmaceutical biodistribution in myeloma and amyloidosis are presented and discussed, with a bone tracer depicting the heart and a heart tracer depicting the bones.

The effect of emotional content on visual recognition memory: a PET activation study.

The emotional content of stimuli can enhance memory for those stimuli. This process may occur via an interaction with systems responsible for perception and memory or via the addition of distinct brain regions specialized for emotion which augment mnemonic processing. We performed an 15O PET study to identify neuroanatomical systems which encode visual stimuli with strong negative emotional valence compared to stimuli with neutral valence. Subjects also performed a recognition memory task for these same images, mixed with distracters of similar emotional valence. The experimental design permitted us to independently test effects of emotional content and recognition memory on regional activity. We found activity in the left amygdaloid complex associated with the encoding of emotional stimuli, although this activation appeared early in the scanning session and was not detectable during recognition memory. Visual recognition memory recruited the right middle frontal gyrus and the superior anterior cingulate cortex for both negative and neutral stimuli. An interaction occurred between emotional content and recognition in the lingual gyrus, where greater activation occurred during recognition of negative images compared to recognition of neutral images. Instead of distinct neuroanatomical systems for emotion augmenting memory, we found that emotionally salient stimuli appeared to enhance processing of early sensory input during visual recognition.

Immunolymphoscintigraphy in breast cancer: evaluation using 131I-labeled monoclonal antibody B72.3.

Noninvasive axillary lymph node staging was investigated using [131I]murine monoclonal antibody B72.3 in 16 patients with breast cancer scheduled for axillary dissection. [131I]B72.3 was injected into ipsilateral finger webs or around the breast biopsy. Scintigraphy to 72 h and gamma-counting/immunohistochemistry of nodes were performed. Specific antibody uptake (%ID/g) and the ratio of specific:nonspecific antibody uptake were not significantly different in tumor-positive versus tumor-negative nodes, suggesting that [131I]B72.3 is unsuitable to discriminate axillary node tumor involvement.

Alteration of corticothalamic perfusion ratios during a PTSD flashback.

We performed a single photon emission computed tomography (SPECT) study of patients with posttraumatic stress disorder (PTSD) by measuring changes in regional cerebral blood flow (rCBF) during provocation by combat stimuli. A single patient experienced an actual flashback following exposure to combat sounds, exhibiting tearfulness, diaphoresis, tachypnea, and severe agitation. Results from his SPECT study demonstrated a dramatically altered ratio of cortical to subcortical perfusion during the flashback but not during the control scan. This altered pattern, which showed a peak of activity in the thalamus, was not consistent with global rCBF changes induced by hyperventilation. The perfusion pattern during the patient's control scan was qualitatively indistinguishable from any of the SPECT scans obtained for the other patients. This single case suggests a possible role for corticothalamic dysfunction in flashbacks.

The role of scintigraphy in the evaluation of fever of unknown origin.

Nuclear medicine imaging techniques are an important adjunct to other currently used modalities in the evaluation of patients with fever of unknown origin. Bone scanning performed with technetium-labeled phosphonate agents may identify osteomyelitis when plain radiography fails and may disclose sites of joint inflammation or unsuspected osseous tumor metastasis. Indium-labeled autologous leukocytes localize at sites of inflammation in the same manner as unlabeled leukocytes. Gallium citrate accumulates in areas of inflammation and in some tumors, most notably lymphomas. In most cases, scintigraphy is best used to determine the location of a lesion rather than to specifically identify the pathologic process.

Technetium-99m-red blood cell scintigraphy in the localization of nonenteric hemorrhage.

Rapid detection and localization of the bleeding site(s) are important factors in successful management of actively bleeding patients. Technetium-99m-red blood cell imaging is a sensitive, noninvasive modality commonly used for localization of gastrointestinal bleeding. Outside the gastrointestinal tract, experience with this technique has been limited. In this report, we present three cases of nonenteric bleeding successfully located using 99mTc red blood cells. The current literature regarding the scintigraphic localization of nonenteric bleeding is reviewed and discussed.

Imaging, dosimetry, and radioimmunotherapy with iodine 131-labeled anti-CD37 antibody in B-cell lymphoma.

PURPOSE: This study was undertaken to evaluate the tumor targeting, toxicity, and therapeutic potential of the anti-B-cell-reactive monoclonal antibody MB-1 (anti-CD37) labeled with iodine 131 given in a nonmarrow ablative dose range in B-cell lymphoma patients who relapsed after chemotherapy. PATIENTS AND METHODS: Twelve patients with MB-1-reactive tumors were infused first with 40 mg of trace-labeled (3 to 7 mCi) MB-1. Ten patients who had no serious toxicity postinfusion and who had successful tumor imaging on serial gamma scans then received at least one 40-mg radioimmunotherapy (RIT) dose (25 to 161 mCi). Tracer estimates of delivered whole-body dose (WBD) were used in prescribing a millicurie RIT dose for seven patients. RESULTS: Eleven patients had positive tumor imaging after a tracer dose, including patients with bulky tumors and/or large tumor burdens (> or = 1 kg) +/- splenomegaly. However, overall sensitivity for the detection of known tumor sites was only 39%. In six of eight patients with dose-assessable tumors, the radiation dose to at least one tumor was 1.1 to 3.1 times higher than to any normal organ, excluding the spleen for a 40-mg tracer dose. Tracer-dose toxicities included reversible glossal edema in one patient, grade 3 hepatic transaminasemia in another, and early drops in both circulating B and T cells (with decreases in B cells more pronounced) in nearly all patients. RIT toxicity was primarily myelosuppression (especially thrombocytopenia), which had a delayed onset and protracted recovery (without significant recovery until at least 2 months post-RIT). Grade 3 myelosuppression in two of two patients who were treated at a tracer-projected 50-cGy WBD level (133 and 149 mCi) precluded further planned RIT dose escalation. Less myelosuppression was generally observed in patients who were treated at < or = 40-cGy WBD levels. Antimouse antibodies developed in two patients. Six patients had tumor responses post-RIT. Four had responses that lasted more than 1 month (2 to 6 months), which included one complete response, one partial response, one minor response, and one mixed response. Responses seemed to occur more frequently in imaged tumors than in nonimaged tumors. The most durable response occurred in a patient who had the best antibody targeting to tumor. CONCLUSIONS: Although 131I-MB-1 has limited diagnostic value, it can produce tumor responses at nonmarrow ablative RIT doses. Further studies that focus on improving tumor targeting with this or other B-cell-reactive radiolabeled antibodies and on ameliorating the myelosuppression associated with the RIT-dosing approach used in this trial are warranted.

Bone mineral density of the axial skeleton in acromegaly.

Acromegaly is characterized by growth hormone (GH) hypersecretion and insulin-like growth factor-I (IGF-I) excess, both of which stimulate osteoblast proliferation. At diagnosis, GH excess has usually been present for years. Furthermore, impaired gonadotropin secretion with hypogonadism is frequent. To date, studies of changes in bone mineral density (BMD) in acromegaly have been limited and the available data inconsistent. To investigate the effects of GH excess on proximal femur and lumbar spine BMD, a case series of 25 patients with acromegaly (8 eugonadal, 17 hypogonadal) documented by high plasma GH and IGF-I concentrations was studied. BMD was measured using dual-photon absorptiometry, hormonal and biochemical measurements, which included GH, IGF-I, serum calcium, phosphate, alkaline phosphatase, 1,25 dihydroxy vitamin D and urinary calcium and hydroxyproline excretion. Seven patients were re-studied after IGF-I was suppressed for six months by the somatostatin analog 201-995 (five patients) or pituitary adenomectomy (two patients). BMD was normal in 22 patients and was decreased at one site each in one eugonadal and two hypogonadal patients. BMD was similar between the eugonadal and hypogonadal groups at all sites. Urinary hydroxyproline excretion was equally increased in both groups. There was no correlation between any of the hormonal or biochemical parameters and the age, sex, race and body mass index matched Z-scores of BMD at any site. Following normalization of IGF-I for 6 mo in seven patients, there was no significant change of BMD. We conclude that proximal femoral and lumbar spine BMD is normal in most patients with active acromegaly, including those who are hypogonad. Successful treatment of acromegaly does not result in major short-term changes in BMD.

Distribution of [32P]-chromic phosphate colloid in cystic brain tumors.

To suppress cyst formation in 42 brain tumors, 32P has been stereotactically instilled in doses calculated to deliver 20,000-40,000 rad to the cyst wall, assuming uniform dispersal of the radioisotope. However, samples of cyst fluid obtained at varying intervals after injection showed lower than expected activity levels, suggesting early 'plating' of 32P. To accommodate this phenomenon, a surface-area-dependent dosimetric calculation is compared with a volume-dependent calculation which assumes uniform dispersal. These two approaches represent lower and upper extremes. It appears that in small cysts there is less difference in the required administered dose, but in larger cysts potentially very large differences exist and caution should be exercised if uniform suspension is assumed.