Impact of Single-Time-Point Estimates of 177Lu-PRRT Absorbed Doses on Patient Management: Validation of a Trained Multiple-Linear-Regression Model in 159 Patients and 477 Therapy Cycles.

Dosimetry after 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) enables estimation of radiation doses absorbed by normal organs and target lesions. This process is time-consuming and requires multiple posttreatment studies on several subsequent days. In a previous study, we described a newly developed multiple-linear-regression model to predict absorbed doses (ADs) from a single-time-point (STP) posttreatment study acquired 168 h after the first infusion and 24 h after the following ones, with similar results to the standard multiple-time-point (MTP) protocol. The present study aimed to validate this model in a large patient cohort and to assess whether STP dosimetry affects patient management decisions compared with our MTP protocol. Methods: Quantitative 177Lu-DOTATATE SPECT/CT post-PRRT data from 159 consecutive patients (172 therapies, 477 therapy cycles) were retrospectively analyzed. ADs obtained from an STP model were compared with those obtained using an MTP model. We evaluated the impact of the STP model on the decision on whether PRRT should be stopped because of an expected kidney AD exceeding the safety threshold. We hypothesized that patient management based on the STP model does not differ from that based on the MTP model in at least 90% of the cases. Results: There was no difference in management decisions between the MTP and STP models in 170 of 172 therapies (98.8%). A Fisher χ2 test for combined probabilities produced a composite P value of 0.0003. Mean cumulative AD relative differences between the STP and MTP models were 0.8% ± 8.0%, -7.7% ± 4.8%, 0.0% ± 11.4%, -2.8% ± 6.3%, and -2.1% ± 18.4% for kidneys, bone marrow, liver, spleen, and tumors, respectively (Pearson r = 0.99 for all), for patients who underwent 4 therapy cycles. Similar results were obtained with fewer therapy cycles. Conclusion: Estimated radiation ADs and patient management decisions were similar with the STP and MTP models. The STP model can simplify the dosimetry process while also reducing scanner and staff time and improving patient comfort.

Simple model for estimation of absorbed dose by organs and tumors after PRRT from a single SPECT/CT study.

BACKGROUND: Following each cycle of peptide receptor radionuclide therapy (PRRT), absorbed doses by tumors and normal organs are typically calculated from three quantitative single-photon emission computed tomography (SPECT)/computed tomography (CT) studies acquired at t1 = 24 h, t2 = 96 h, t3 = 168 h after the first cycle of treatment and from a single study at t1 after the subsequent cycles. In the present study, we have assessed the feasibility of a single SPECT/CT study after each PRRT cycle using a trained multiple linear regression (MLR) model for absorbed dose calculation and have evaluated its impact on patient management. Quantitative [177Lu]-DOTA-TATE SPECT/CT data after PRRT of seventy-two consecutive metastatic neuroendocrine tumors patients were retrospectively evaluated. A set of 40 consecutive studies was used to train the MLR model. The two independent variables of the model included the time of imaging after administration of the treatment and the radiopharmaceutical activity concentration in a given  organ/tumor. The dependent variable was the dose absorbed by the organ/tumor obtained with the standard protocol. For bone marrow dosimetry, the independent variables included the time of imaging, and the blood and remainder of the body activity concentration. The model was evaluated in 32 consecutive patients. Absorbed doses were assessed for kidneys, bone marrow, liver, spleen and tumor sites. RESULTS: There was no difference in management decisions, whether PRRT can be safely continued or not because unsafe absorbed dose to risk organs between the standard and the MLR model-based protocol using a single SPECT/CT study performed at t3 = 168 h after the first cycle and at t1 = 24 h after the subsequent cycles. Cumulative absorbed doses were obtained with mean relative differences of - 0.5% ± 5.4%, 1.6% ± 15.1%, - 6.2% ± 7.3%, - 5.5% ± 5.8% and 2.9% ± 12.7% for kidneys, bone marrow, liver, spleen and tumors, respectively (Pearson's r correlation coefficient 0.99, 0.91, 0.99, 0.99 and 0.97, respectively). CONCLUSION: Dosimetry calculations using a MLR model with a single SPECT/CT study are in good agreement with the standard protocol, while avoiding the use of dosimetry software and enabling improved patient comfort and reduced scanner and staff time.

[RADIONUCLIDE THERAPY OF NEUROENDOCRINE TUMORS - IMPROVEMENTS IN THE PROTOCOL FOR MEASUREMENT OF PATIENT RADIATION EXPOSURE].

AIMS: The aim of this study was to evaluate the predictive power of the absorbed dose to kidneys after the first course of treatment with [177Lu]-DOTA-TATE on the cumulative kidney absorbed dose after 3 or 4 cycles of treatment. BACKGROUND: Peptide receptor radionuclide therapy (PRRT) with [177Lu]-DOTA-TATE is an effective treatment for somatostatin receptor positive neuroendocrine tumors (NETs). Post-treatment scans (PTS) are required after each cycle of treatment for personalized radiation dosimetry in order to calculate the dose to organs and tumors and to ensure a cumulative absorbed dose to kidneys under a safety threshold of 25 Gy. METHODS: A total of 187 patients who completed treatment and underwent PTS for dosimetry calculation were included in this retrospective study. The correlation between the cumulative absorbed dose to the kidneys after completion of treatment and the absorbed dose after the first cycle(s) was studied. Multilinear regression analysis was performed to predict the cumulative absorbed dose by the kidneys in the subsequent cycles. An algorithm for the follow-up of the kidney absorbed dose is proposed. RESULTS: When the absorbed dose to kidneys after the first cycle of treatment is below 5.6 Gy, four cycles of treatment can be safely administered with a cumulative dose less than 25 Gy (p < 0.1). For the remaining patients, the cumulative dose absorbed after 3 or 4 cycles of treatment can be predicted after the second cycle of treatment. This protocol enabled early decisions on the number of treatment cycles and reduced the number of post-treatment SPECT/CT studies for dosimetry in 34% of patients, as well as hospitalization time for 56% of the treatment cycles. CONCLUSIONS: Assessment of the kidney absorbed dose after PRRT can be simplified with the algorithm presented in this study. This approach enabled early decisions on the number of therapy cycles in 75% of patients. DISCUSSION: The validity of these results is limited to the protocol of dosimetry calculation used in our institution. Implementation in other centers may require standardization of the acquisition parameters and the dosimetry protocol.

Highly favourable outcomes with peptide receptor radionuclide therapy (PRRT) for metastatic rectal neuroendocrine neoplasia (NEN).

PURPOSE: Rectal neuroendocrine neoplasia (NEN) is more common than other NEN origins, but is less commonly metastatic. However, when present, distant disease carries a particularly poor prognosis. Evidence guiding optimal treatment of such patients is lacking. We assessed PRRT outcomes in patients with somatostatin receptor (SSTR) positive metastatic rectal NEN from two referral centres. METHODS: Patients treated with PRRT were retrospectively reviewed. Morphologic (RECIST 1.1), SSTR imaging responses and toxicity were assessed 3 months post-PRRT. Kaplan-Meier estimate was used to determine progression-free survival (PFS) and overall survival (OS) from start of PRRT. RESULTS: Twenty-seven consecutive patients (M = 20, age 31-81 years) were reviewed. The majority (70%) had ENETs grade 2 disease (19 patients), three had Grade 3, one Grade 1, and four not documented. Overall, 63% (10/16 patients with available FDG PET/CT) had FDG avid disease. Twenty-six patients were treated for disease progression. Most had 177Lu-DOTA-octreotate with median cumulative activity of 30 GBq, median four cycles. 14 patients had radiosensitising chemotherapy (5FU or capecitabine). At 3 months post-PRRT, CT disease control rate (DCR) was 96%: partial response was observed in 70% (19/27) and stable disease in 26%. All but one had partial SSTR imaging response. The median PFS was 29 months. Ten patients died, with median overall survival 81 months with a median follow-up of 67 months. Seventeen patients had further treatments after initial PRRT (10 had further cycles of PRRT). Three patients had grade 3 lymphopenia, without significant renal toxicity, MDS or leukaemia. CONCLUSION: Our results indicate high efficacy and morphologic responses with minimal toxicity and very encouraging survival from PRRT in patients with metastatic rectal NEN despite the adverse prognostic features of this cohort. Further prospective PRRT trials are warranted in this subgroup.

Predictive power of the post-treatment scans after the initial or first two courses of [177Lu]-DOTA-TATE.

BACKGROUND: The aim of this study was to evaluate the predictive power of the absorbed dose to kidneys after the first course of treatment with [177Lu]-DOTA-TATE for neuroendocrine tumors (NETs) on the cumulative kidney absorbed dose after 3 or 4 cycles of treatment. Post-treatment scans (PTS) are acquired after each cycle of peptide receptor radionuclide therapy (PRRT) with [177Lu]-DOTA-TATE for personalized radiation dosimetry in order to ensure a cumulative absorbed dose to kidneys under a safety threshold of 25 Gy. One hundred eighty-seven patients who completed treatment with [177Lu]-DOTA-TATE and underwent PTS for dosimetry calculation were included in this retrospective study. The correlation between the cumulative absorbed dose to kidneys after the completion of treatment and the absorbed dose after the first cycle(s) was studied. Multilinear regression analysis was done to predict the cumulative absorbed dose to the kidneys of the subsequent cycles, and an algorithm for the follow up of kidney absorbed dose is proposed. RESULTS: Patients whose absorbed dose to kidneys after the first cycle of treatment is below 5.6 Gy can receive four cycles of treatment with a cumulative dose less than 25 Gy (p < 0.1). For the other patients, the cumulative absorbed dose after 3 or 4 cycles of treatment can be predicted after the second cycle of treatment to allow for an early decision regarding the number of cycles that may be given. CONCLUSIONS: The follow up of kidney absorbed dose after PRRT can be simplified with the algorithm presented in this study, reducing by one-third the number of post-treatment scans and reducing hospitalization time for more than half of the treatment cycles.

Diagnostic Computed Tomography Coregistration With In-111-DTPA-Octreotide Single Photon Emission Tomography/Low-Dose Computed Tomography.

OBJECTIVES: In-111-DTPA-octreotide (OctreoScan) is still pivotal for neuroendocrine tumor imaging, despite the introduction of Ga-68-octreotide tracers. Low-dose computed tomography (LDCT) assists in the localization of SPECT findings but often results in uncertain interpretation. This retrospective study evaluates the impact of coregistration of In-111-DTPA-octreotide SPECT/LDCT with diagnostic CT on interpretation. METHODS: Thirty-five consecutive studies, in which coregistration was performed because of uncertain interpretation, were evaluated. Presence of somatostatin receptors was categorized retrospectively as definitely positive, probably positive, probably negative, or definitely negative with and without rigid registration with diagnostic CT, and possible added value of coregistration was evaluated. RESULTS: Coregistration was performed in 35 studies. However, on subsequent reading, 4 SPECT/CTs yielded definite results and were omitted. Coregistration was helpful in 30 of the remaining 31 cases, changing reading to definitely positive (7) or to definitely negative (23). In 13 of the 23 cases, diagnosis changed from probably positive to definitely negative. Coregistration contributed in 42 of 48 sites, with greatest benefit in the liver (13/14), pancreas (10/10), and lymph nodes (6/6). CONCLUSIONS: Coregistration is becoming increasingly easier and may be utilized when SPECT/LDCT is inconclusive.

Neuroendocrine tumor imaging with 68Ga-DOTA-NOC: physiologic and benign variants.

OBJECTIVE: Imaging with (68)Ga-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotide analogs has become an important modality in patients with neuroendocrine tumors (NETs). In addition to high uptake in NET lesions, prominent physiologic radiotracer activity has been reported in the pituitary gland, pancreas, adrenal glands, liver, and spleen, and faint activity has been reported in the thyroid and gastrointestinal tract. This article describes previously unknown sites of 68Ga-DOTA-1-NaI3-octreotide (NOC) uptake unrelated to NETs. MATERIALS AND METHODS: One hundred eighty-two patients (96 female and 86 male patients; age range, 4-89 years) with documented (n=156) or suspected (n=26) NETs underwent 207 68Ga-DOTA-NOC PET/CT studies. Studies were retrospectively reviewed for the presence, intensity, and localization of foci of increased uptake that were further correlated with findings on additional imaging studies and clinical follow-up for a period of 4-32 months. RESULTS: Uptake of 68Ga-DOTA-NOC not identified as NET or known physiologic activity was detected in 297 sites with confirmation in 149 of 207 studies (72%). The most common location of non-NET-related 68Ga-DOTA-NOC-avid sites was in small lymph nodes, followed by prostate, uterus, breasts, lungs, brown fat, musculoskeletal system, and other sites, including oropharynx, pineal body, thymus, aortic plaque, genitalia, surgical bed, and subcutaneous granuloma. Intensity of uptake in non-NET-related 68Ga-DOTA-NOC-avid sites ranged in maximum standardized uptake value from 0.8 to 10.5. CONCLUSION: Previously unreported benign sites of 68Ga-DOTA-NOC uptake were found in the majority of studies, suggesting the presence of somatostatin receptors in physiologic variants or processes with no evidence of tumor. Knowledge of increased tracer uptake in non-NET-related sites is important for accurate interpretation and for avoiding potential pitfalls of 68Ga-DOTA-NOC PET/CT.

Localization of parathyroid adenoma by ¹¹C-choline PET/CT: preliminary results.

PURPOSE: This prospective pilot study was aimed to evaluate ¹¹C-choline PET/CT (choline) as a tool for localization of parathyroid adenoma (PTA). METHODS: Forty patients with biochemical hyperparathyroidism underwent choline and 99mTc-MIBI imaging within a median interval of 56 days. Choline and MIBI images were analyzed and correlated with each other, with additional modalities such as ultrasound, CT, MRI, and with surgical findings, when available. RESULTS: Thirty-seven of forty cases were choline-positive, and 3 were choline-negative. Choline uptake on PET was identified with corresponding nodules on CT of the PET/CT, yielding precise localization. Twenty of thirty-seven foci were located in typical sites in the neck, and 17 were ectopic. Clear visualization of PTA was achieved in 33 of 37, whereas findings in 4 cases were suspicious for PTA. MIBI was positive in 33 of 40 cases (22 clearly positive, 11 suspicious). In 29 of 40 cases, choline and MIBI were concordant, but choline findings were clearer in 9 of these 29 studies.At the time of writing, 27 patients had undergone surgery. In 24 cases, there was complete matching of choline with surgical findings of PTA. Overall in 23 cases, both choline and MIBI matched surgical findings of PTA. In 1 case, PTA was correctly localized on choline but not on MIBI, and in 2 cases, neither choline nor MIBI corresponded to the surgical findings. CONCLUSIONS: These preliminary results indicate that the combined functional and anatomical modality of choline PET/CT is a promising tool for PTA localization, providing clearer images than MIBI, equal or better accuracy, and quicker and easier acquisition.

Ga-68 DOTA-NOC uptake in the pancreas: pathological and physiological patterns.

OBJECTIVE: Gallium-68 (Ga-68) DOTA-1-NaI3-octreotide (DOTA-NOC) positron emission tomography (PET)/computed tomography (CT) is increasingly used for neuroendocrine tumors (NETs), often found primarily in the pancreas. However, physiologic uptake of DOTA-NOC has been described in the uncinate process of the pancreas. We studied DOTA-NOC uptake in this organ. MATERIALS AND METHODS: Ninety-six patients underwent 103 DOTA-NOC scans, with pathology-proven pancreatic NET (n = 40) and nonpancreatic NET or biochemical suspicion of NET (n = 63). RESULTS: DOTA-NOC uptake was detected in 35 documented pancreatic tumor sites (SUV: 5.5-165; mean: 25.7 ± 28.8; median: 17.8). Among 63 cases without previous known pathology, uptake was suspicious for tumor in 24 sites (SUV: 4.7-35; mean 16.3 ± 8.0; median: 14.1), and in 38 sites, it was judged as physiological, generally lower relative to adjacent structures (SUV: 2.2-12.6; mean: 6.6 ± 2.2; median: 6.2). In 24 scans with suspected tumor and in 37 of 38 scans with physiological uptake, diagnostic computed tomography or magnetic resonance imaging or endoscopic ultrasonography failed to detect tumor. CONCLUSIONS: Pancreatic DOTA-NOC uptake must be interpreted with caution, and further studies are required.

68Ga-DOTA-NOC PET/CT imaging of neuroendocrine tumors: comparison with ¹¹¹In-DTPA-octreotide (OctreoScan®).

PURPOSE: Recent data have indicated that 68Ga-DOTA-NOC positron emission tomography/X-ray computed tomography (PET/CT) may yield improved images in a shorter acquisition protocol than ¹¹¹In-DTPA-octreotide (OctreoScan®, OCT). Therefore, we performed a prospective comparison of 68Ga-DOTA-NOC and OCT for the detection of neuroendocrine tumors (NETs). METHODS: Nineteen patients (eight carcinoid, nine pancreatic NETs, and two NE carcinoma of unknown origin) with previous positive OCT scans underwent 68Ga-DOTA-NOC PET/CT and OCT single-photon emission computed tomography imaging for staging or follow-up. Findings were compared by region and verified with conventional imaging. RESULTS: All images of both modalities demonstrated focal uptake, often at multiple sites. 68Ga-DOTA-NOC images were clearer than OCT images, facilitating interpretation. Similar foci were identified with both modalities in 41 regions, with additional foci on 68Ga-DOTA-NOC in 21 and on OCT in 15 regions. CT, magnetic resonance imaging, or ultrasound confirmed the concordant findings in 31 of 41 regions and findings seen with 68Ga-DOTA-NOC only in 15 of 21 regions. Findings seen with OCT only were less clear and were only confirmed in 4 of 15 regions. 68Ga-DOTA-NOC had impact on staging in four patients and on management in three patients. CONCLUSIONS: Although 68Ga-DOTA-NOC and OCT images were similar, in this study, 68Ga-DOTA-NOC demonstrated more true positive tumor foci and was better tolerated by patients. This direct comparison supports replacement of OCT with 68Ga-DOTA-NOC-PET/CT in the evaluation of NETs.

Cerebral perfusion after a 2-year remission in major depression.

Although patients suffering from major depression respond to antidepressant treatment within several weeks, full reinstatement of premorbid capabilities requires much longer. Nevertheless, most research in major depression seeking the pathophysiological correlates of remission has focused upon the acute post-treatment period. Brain imaging research offers no exception. We have recently shown that cerebral perfusion in depressed patients responding to 6-wk antidepressant medication increases in parieto/cerebellar regions and becomes similar to that of healthy control subjects. We now present technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography (99mTc-HMPAO SPECT) data collected from 11 of these patients 2 years in remission. Images were analysed using Statistical Parametric Mapping. After 2 years, perfusion normalization found immediately after treatment was maintained, with further increases in frontal and decreases in parieto/cerebellar regions. These findings suggest that perfusion increases in parieto/cerebellar regions may be involved in acute response to treatment whereas increases in frontal regions may be related to its consolidation.

Added value of SPECT/CT for correlation of MIBG scintigraphy and diagnostic CT in neuroblastoma and pheochromocytoma.

OBJECTIVE: In pheochromocytoma and neuroblastoma, pathologic findings on metaiodobenzylguanidine (MIBG) scintigraphy (planar and SPECT) and on diagnostic CT are sometimes difficult to correlate. Furthermore, CT reading may be impaired by anatomic distortion after surgery or irradiation and if contrast agent is not injected. The present study evaluates the impact of SPECT/CT fusion images on correlation and image analysis of both techniques. MATERIALS AND METHODS: Eleven patients, three adults (age range, 27-64 years) with pheochromocytoma and eight children (age range, 16-72 months) with neuroblastoma, underwent 15 (123)I-MIBG scintigraphy (whole body and SPECT/CT) and diagnostic CT during follow-up after treatment, with a time interval of 2 to 30 days (mean, 12 days) between MIBG scintigraphy and diagnostic CT. The diagnostic CT scans were read twice: blindly and with knowledge of the SPECT/CT findings. The scintigraphic and anatomic data were subsequently compared and were verified by clinical outcome. RESULTS: Of 15 imaging studies, there were nine cases of discordance between SPECT/CT and diagnostic CT, whereas concordant findings of planar MIBG and diagnostic CT were observed in six studies. Overall, SPECT/CT provided additional information in eight of the 15 cases (53%) and in eight of nine discordant studies (89%). In one case of pheochromocytoma in which anatomy was distorted by previous surgery and contrast agent was not injected, SPECT/CT findings guided the diagnostic CT that had initially misinterpreted the right adrenal gland as the inferior vena cava. In three of 11 studies performed for neuroblastoma, SPECT/CT facilitated the diagnostic CT reading: in one study, a small paravertebral thickening was overlooked at blind CT reading and in another case, SPECT/CT localized and characterized a soft-tissue mass medial to the iliac bone, which was missed on diagnostic CT in an area of difficult differential anatomy (bowel loops and eventual involved lymph nodes). In the third case, SPECT/CT directed the diagnostic CT to the MIBG abnormality after multiple surgical procedures. In these four cases, MIBG SPECT/CT allowed for localization of the pathologic site that was difficult to visualize on diagnostic CT. In four additional neuroblastoma studies in which a residual mass was present on diagnostic CT, planar MIBG scintigraphy was negative. SPECT/CT, focused on the area of the diagnostic CT abnormality, showed no focal MIBG uptake, thus increasing the diagnostic certainty of remission. CONCLUSION: In cases of equivocal diagnostic CT, SPECT/CT bridges the gap between MIBG scintigraphy and diagnostic CT, with guidance of the diagnostic CT and characterization of its findings. In this small series, MIBG SPECT/CT increased the diagnostic certainty in 89% of discordant studies.

99mTc-HMPAO SPECT study of cerebral perfusion after treatment with medication and electroconvulsive therapy in major depression.

UNLABELLED: Compromised regional cerebral blood flow (rCBF) in major depressive disorder may be partly reversed by successful antidepressant treatment. However, it is not known if the reversal of rCBF compromise is dependent on the mode of antidepressant treatment. The current study aimed to address this question. METHODS: Thirty-three patients (19 women and 14 men; mean age +/- SD, 53 +/- 16 y) with moderate major depressive disorder were studied before 6 wk of treatment with tricyclic antidepressants, selective serotonin reuptake inhibitors, or a course of electroconvulsive therapy, and 31 of these patients were also studied afterward. A comparison group of 25 healthy volunteers (13 women and 12 men; mean age, 49 +/- 15 y) were studied once. rCBF was assessed using 99mTc-hexamethylpropyleneamine oxime SPECT. Images were analyzed using globally normalized statistical parametric mapping localized to the Montreal Neurologic Institute brain atlas. RESULTS: Baseline rCBF was lower in depressed patients than in controls in the frontal cortex and subcortical nuclei bilaterally. A response to medication was associated with normalization of rCBF deficits, whereas a response to electroconvulsive therapy was associated with an additional rCBF decrease in the parietotemporal and cerebellar regions bilaterally. CONCLUSION: Hypoperfusion in major depressive disorder largely normalizes after a response to pharmacotherapy. Perfusion changes after a response to electroconvulsive therapy may follow a different course.

Brain SPECT study of common ground between hypothyroidism and depression.

Hypothyroidism and major depressive disorder (MDD) share neuropsychiatric features. Cerebral perfusion deficits are found in both disorders. We compared regional cerebral blood flow (rCBF) in hypothyroidism and MDD to determine if clinical similarities are mediated by common neurocircuitry. Ten hypothyroid and 10 depressed patients underwent 99mTc-HMPAO-SPECT and clinical evaluation before and after response to respective treatments. Ten healthy controls underwent a similar, single, evaluation. Before treatment, rCBF in hypothyroid and depressed patients was lower than in controls, in posterior and anterior aspects of the brain respectively. rCBF in hypothyroidism was lower than in MDD in right posterior cingulate and parieto/occipital regions, and higher in frontal, prefrontal and sub-genual regions. Reduced rCBF in pre- and post-central gyri was found in both groups. Following treatment, rCBF in depressed patients increased and normalized, but remained unchanged in hypothyroidism. Affective symptoms in hypothyroidism may be mediated by neurocircuitry different from that of major depression.

Single-photon emission computed tomography/computed tomography in endocrinology.

The introduction of fusion of functional and anatomical imaging modalities into the field of endocrinology led to a major breakthrough in diagnosis, staging, and follow-up of patients with endocrine tumors. The management of endocrine tumors is based on a wide variety of conventional techniques, including computed tomography, ultrasound, or magnetic resonance imaging, and on scintigraphic functional techniques, associated with unique uptake and transport mechanisms and with the presence of high density of membrane receptors on some of these tumors. Anatomical modalities provide accurate detection and localization of morphological abnormalities, whereas nuclear medicine studies reflect the pathophysiological status of the disease process. Lack of structural delineation and relatively low contrast hamper the precise anatomical localization of the abnormal functional findings in the presence of potential concurrent foci related to the physiological biodistribution of the radiotracer or to processes unrelated to the evaluated disease entity. The notion that anatomical high-resolution and functional imaging data act as complementary methods led to various combination techniques of these modalities. However, coregistration of the functional and anatomical data after the acquisition of the 2 imaging modalities on separate machines, in different sessions, fails to provide accurate alignment of data, and the mathematical modeling is too cumbersome to be used on a routine basis. In contrast, hybrid imaging devices of single-photon emission computed tomography/computed tomography in a single gantry enable the sequential acquisition of the two modalities, with subsequent merging of data into a composite image display. These hybrid studies have led to a revolution in the field of imaging, providing clinically relevant information that is not apparent on separate images. The present review evaluates the contribution of the integrated single-photon emission computed tomography/computed tomography technology to image analysis and management of patients with endocrine tumors.

Technetium-99m-MIBI SPECT/CT in primary hyperparathyroidism.

The novel trend toward focused parathyroidectomy requires precise preoperative localization of the parathyroid adenoma in patients with primary hyperparathyroidism (PHPT). The present study evaluated the impact of hybrid single photon emission computed tomography/computed tomography (SPECT/CT), using 99mTc-sestamibi (MIBI), on the surgical management of these patients. In a retrospective study of 36 patients with PHPT, SPECT/CT was undertaken when planar 99mTc-MIBI scintigraphy was negative or when an ill-defined focus in the neck or an ectopic site on planar views was visualized. Imaging data were compared with intraoperative findings, and the incremental value of SPECT/CT to lesion localization and surgical procedure was assessed. Three patients with both negative planar and SPECT/CT studies subsequently underwent bilateral neck exploration, with multiglandular hyperplasia diagnosed in two patients and a parathyroid adenoma in one. Of 33 patients with a positive MIBI study, parathyroid adenoma was confined to the neck in 23 patients and to the lower neck-mediastinum in 10. SPECT/CT facilitated the surgical exploration of all 10 ectopic parathyroid adenomas and 4 of 23 cervical parathyroid adenomas, the latter four either at reexploration or in patients with nonvisualization of the thyroid after thyroidectomy. SPECT/CT contributed to the localization of parathyroid adenomas in patients with PHPT and to planning the surgical exploration in 14 of 36 (39%) patients, predominantly those with ectopic parathyroid adenomas or who had distorted neck anatomy.

Short- and long-term outcome of lung volume reduction surgery. The predictive value of the preoperative clinical status and lung scintigraphy.

The NETT study assessed the benefits of lung volume reduction surgery (LVRS) versus medical treatment. However, data is available only on the early outcome of LVRS (24 months). We evaluate the factors affecting the outcome at one-year and up to 6 years after LVRS. Thirty-seven patients underwent LVRS. Thirty-five patients, who survived the operation for at least one-year, were followed up to 6 years. Patients' laboratory, clinical and scintigraphic data before surgery were reviewed retrospectively, and follow-up at one-year and at the end of data collection. Successful LVRS with improvement of FEV(1)30% at one-year was observed in 13 of 35 patients. Five of these patients had initial FEV(1) values of <20% of the predicted. The group of patients with improvement was younger as compared to the 22 patients without improvement (P<0.005). The younger age group used less supplemental oxygen and had a PDiff of >23%. Combinations of age under 60 years and PDiff >23% were a favorable factor (P<0.002) for successful LVRS. Thirty-four patients were followed up to 6 years. Fifteen of the 34 patients (44.1%) remained well. Use of supplemental oxygen before surgery, and FEV(1) improvement of 30% at one-year after surgery were good prognostic factors. We concluded that the long-term success of LVRS is affected by non-dependence on oxygen supplementation before surgery, and the one-year post-surgical improvement of FEV(1) (30%). Based on our findings, the subgroup of patients below 60 years old with severe disease (FEV(1)<20%) and heterogeneous upper lobe emphysema (Pdiff>23%) has improved outcome.

In vivo measurement of brain monoamine oxidase B occupancy by rasagiline, using (11)C-l-deprenyl and PET.

UNLABELLED: In recent years, monoamine oxidase B (MAO-B) inhibitors have become widely used in the treatment of early-stage Parkinson's disease. (11)C-l-deprenyl PET has been used by others to characterize MAO-B ligands in terms of their in vivo potency toward MAO-B and duration of action. In this study, we used (11)C-l-deprenyl PET to demonstrate the specific binding characteristics of the new irreversible selective MAO-B inhibitor rasagiline in 3 healthy volunteers. METHODS: The healthy volunteers received 1 mg of rasagiline daily for 10 d. Dynamic (11)C-l-deprenyl PET brain scans were acquired before the first treatment (scan 1) and immediately (scan 2), 2-3 wk (scan 3), and 4-6 wk (scan 4) after the final treatment. RESULTS: On scan 1, all subjects showed the highest l-deprenyl uptake in the thalamus and basal ganglia, with fairly high activity also in the cortex and cerebellum and much lower activity in the white matter. The areas of high uptake were absent from scan 2, on which activity throughout the brain was comparable to that in white matter, presumably because of blocking of MAO-B binding sites by rasagiline. Gradual recovery toward the baseline state was observed in the weeks after termination of treatment (scans 3 and 4). CONCLUSION: (11)C-l-deprenyl PET showed binding of rasagiline to MAO-B, confirming blocking of MAO-B sites after 10 d of treatment with 1 mg of rasagiline per day, with immediate post-rasagiline treatment tracer uptake and metabolism in the basal ganglia compatible only with nonspecific binding. Subsequent gradual recovery was also seen, with return to near-baseline uptake. This finding is compatible with the known rate of de novo synthesis of MAO-B, confirming the irreversible binding of rasagiline.