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Purpose 225Ac-PSMA-617 has demonstrated good anti-tumor effect as a treatment option for metastatic castration-resistant prostate cancer (mCRPC) patients. No study has previously assessed treatment outcome and survival following 225Ac-PSMA-617 treatment of de novo metastatic hormone-sensitive prostate carcinoma (mHSPC) patients. Based on the potential side effects that are known and explained to the patients by the oncologist, some of the patients refused the standard treatment and are seeking alternative therapies. Thus, we report our preliminary findings in a retrospective series of 21 mHSPC patients that refused standard treatment options and were treated with 225Ac-PSMA-617. Methods We retrospectively reviewed patients with histologically confirmed de novo treatment-naïve bone ± visceral mHSPC that were treated with 225Ac-PSMA-617 radioligand therapy (RLT). Inclusion criteria included an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, treatment-naive bone ± visceral mHSPC, and patients refusal for ADT ± docetaxel, abiraterone acetate, or enzalutamide. We evaluated the response to treatment using prostate-specific antigen (PSA) response and the progression-free survival (PFS) and overall survival (OS) as well as the toxicities. Results Twenty-one mHSPC patients were included in this preliminary work. Following treatment, twenty patients (95%) had any decline in PSA and eighteen patients (86%) presented with a PSA decline of ≥ 50% including 4 patients in whom PSA became undetectable. A lower percentage decrease in PSA following treatment was associated with increased mortality and shorter progression-free survival. Overall, administration of 225Ac-PSMA-617 was well tolerated. The commonest toxicity seen was grade I/II dry mouth observed in 94% of patients. Conclusions Given these favorable results, randomized prospective multicenter trials assessing the clinical value of 225Ac-PSMA-617 as a therapeutic agent for mHSPC administered either as monotherapy or administered concomitant with ADT are of interest.

The prostate bed is one of the common sites of early recurrence of prostate cancer. The currently used PSMA ligands (Forty-six Prostate cancer (mean age 66.7±7.5, range 48-87 years) presenting with biochemical recurrence (median PSA 1.6ng/ml, range 0.1-10.0) underwent non-contrast-enhancedTwenty-four of the 46 (52.2%) patients demonstrated a site of recurrence onZIEL: Das Prostatabett ist eine der häufigsten Stellen für das Auftreten eines frühen Rezidivs bei Prostatakarzinom. Die derzeit verwendeten PSMA-Liganden (68Ga-PSMA-11 und 99mTc-PSMA) werden frühzeitig mit dem Urin ausgeschieden, was zu einer Beeinträchtigung der physiologischen Aktivität in und um die Prostata führt. Dies kann dazu führen, dass Stellen, an denen der Krebs wieder auftritt, verborgen bleiben. 18F-PSMA-1007 hat den Vorteil einer verzögerten Urinausscheidung, sodass die Prostataregion ohne störende physiologische Aktivität untersucht wird. Ziel dieser Studie war es, die diagnostische Leistung von 18F-PSMA-1007-PET/CT bei Patienten mit frühem biochemischem Rezidiv nach definitiver Therapie zu bestimmen.46 Patienten mit Prostatakarzinom (Durchschnittsalter 66,7 ±7,5 Jahre, Bereich 48–87 Jahre) und biochemischem Rezidiv (medianes PSA 1,6ng/ml, Bereich 0,1–10,0) unterzogen sich einer nicht kontrastverstärkten 18F-PSMA-1007-PET/CT. Die PET/CT-Befunde wurden qualitativ und semiquantitativ (SUV24 der 46 Patienten (52,2%) wiesen im 18F-PSMA-1007-PET/CT ein Rezidiv auf. Bei 15 (32,6%) dieser Patienten wurde eine oligometastatische Erkrankung festgestellt. Von diesen wiesen 10 (37,5%) ein intraprostatisches Rezidiv auf, bei 11 (45,8%) wurde ein Lymphknotenbefall festgestellt, während 2 Patienten Knochenmetastasen aufwiesen. Die Detektionsraten betrugen 31,3% für PSA-Werte von 0–0,5, 33,3% für 0,5–1, 55, 6% für 1–2 und 72,2% für2. Sieben der positiven Patienten (29,2%) waren bei der konventionellen Bildgebung als negativ oder grenzwertig beschrieben worden. Für PSA wurde ein optimaler Cut-off-Wert von 1,3ng/ml ermittelt.18F-PSMA-1007 zeigte eine gute diagnostische Leistung bei der Lokalisation des Rezidivs. Diese Fähigkeit, das Rezidiv bei einem frühen biochemischen Rezidiv zu lokalisieren, wird sich erheblich auf das Patientenmanagement auswirken.

While FDG PET/CT bears a high sensitivity and specificity for the staging of stage III and IV melanoma as well as for the purpose of melanoma recurrence detection, overall results tend to vary from one part of the body to another as well as for melanoma from cutaneous or choroidal origin. In this paper, organ or site-related differences in sensitivity and specificity in melanoma patients, both from cutaneous and choroidal origin, as well as their impact on clinical decision making are discussed. Furthermore, with the advent of immunotherapy for the treatment of malignant melanoma, post-treatment related potential false positive findings have emerged, the knowledge of which is essential for accurate treatment response assessment. These post-treatment related potential false positive findings are summarized in this paper so as to help the nuclear medicine physician in avoiding erroneous interpretation of acquired FDG PET/CT images in melanoma patients receiving immuntherapy.

Hypoxia in cervical cancer has been associated with a poor prognosis. Over the years

Prostate adenocarcinoma (PCa) is a leading cause of mortality. Black males with high-risk PCa have a poorer prognosis compared to white males. Patients with International Society of Urological Pathology (ISUP) Grade Group (GG) 1 and 2 PCa have little potential for metastases post radical prostatectomy. 68Gallium prostate specific membrane antigen (68Ga-PSMA) PET/CT imaging for metastatic PCa is superior to conventional imaging in staging high-risk PCa. No strong evidence is available to support imaging low-risk patients. We aimed to evaluate the value of 68Ga-PSMA PET/CT in black and white South African (BSA and WSA) males with GG1 and 2 PCa at initial staging. We evaluated 25 WSA and 123 BSA males. The image findings were correlated with prostate specific antigen (PSA). PSA levels significantly correlated with both primary tumor and whole-body PSMA-tumor volume (PSMA-TV) and were higher in BSA males. No differences were noted in the occurrence of metastases; however, PSA, seminal vesicle invasion and black race predicted metastases. Our findings suggest higher PSMA expression and tumor burden in BSA with histologically low-risk PCa, and future research with immunohistochemistry evaluation will be essential to confirm these findings.

The use of prostate specific membrane antigen (PSMA) binding agents, labelled with diagnostic and therapeutic radio-isotopes is opening the potential for a new era of personalized management of prostate carcinoma. A wide variety of immunohistochemistry studies have shown PSMA also to be upregulated on the endothelial cells of the neovasculature of a wide variety of other solid tumors where it may facilitate endothelial cell sprouting and invasion through its regulation of lytic proteases that have the ability to cleave the extracellular matrix. Similar to the introduction of PSMA-targeting theranostics in prostate carcinoma, overexpression of PSMA on newly formed tumor vessels may serve as a target for imaging and subsequent treatment of cancer through the use of agents that are capable of blocking PSMA in its function or through PSMA-mediated delivery of chemotherapeutics or radiation agents. In this review, the available data on PSMA expression on tumor neovasculature in human solid tumors assessed by using immunohistochemistry are discussed.

Hypoxia in cervical cancer has been associated with a poor prognosis. Over the years 68Ga labelled nitroimidazoles have been studied and have shown improved kinetics. We present our initial experience of hypoxia Positron Emission Tomography (PET) imaging in cervical cancer with 68Ga-Nitroimidazole derivative and the correlation with 18F-FDG PET/CT and immunohistochemistry. Twenty women with cervical cancer underwent both 18F-FDG and 68Ga-Nitroimidazole PET/CT imaging. Dual-point imaging was performed for 68Ga-Nitroimidazole PET. Immunohistochemical analysis was performed with hypoxia inducible factor-1α (HIF-1α). We documented SUVmax, SUVmean of the primary lesions as well as tumor to muscle ratio (TMR), tumor to blood (TBR), metabolic tumor volume (MTV) and hypoxic tumor volume (HTV). There was no significant difference in the uptake of 68Ga-Nitroimidazole between early and delayed imaging. Twelve patients had uptake on 68Ga-Nitroimidazole PET. Ten patients demonstrated varying intensities of HIF-1α expression and six of these also had uptake on 68Ga-Nitroimidazole PET. We found a strong negative correlation between HTV and immunohistochemical staining (r = −0.660; p = 0.019). There was no correlation between uptake on PET imaging and immunohistochemical analysis with HIF-1α. Two-thirds of the patients demonstrated hypoxia on 68Ga-Nitroimidazole PET imaging.

Purpose 68Ga ligands targeting prostate-specific membrane antigen (PSMA) are rapidly emerging as a significant step forward in the management of prostate cancer. PSMA is a type II transmembrane protein with high expression in prostate carcinoma cells. We prospectively evaluated the use of 68Ga-PSMA positron emission tomography/computed tomography (PET/CT) in patients with prostate cancer and compared the results to those for technetium-99m (99mTc)-10-metacyloyloxydecyl dihydrogen phosphate (MDP) bone scintigraphy (BS). Patients and Methods A total 113 patients with biopsy-proven prostate cancer referred for standard-of-care BS were prospectively enrolled onto this study. 68Ga-PSMA PET/CT was performed after BS. Metastasis diagnosed on each technique was compared against a final diagnosis based on CT, magnetic resonance imaging, skeletal survey, clinical follow-up, and histologic correlation. Results Ninety-one bone lesions were interpreted as bone metastases in 25 men undergoing 68Ga-PSMA PET/CT compared to only 61 lesions in 19 men undergoing 99mTc-MDP BS. Of the 7 bone scans that missed skeletal metastases, 54% of these missed lesions were due to either marrow or lytic skeletal metastases. The median standardized uptake value in all malignant bone lesions was 13.84. 68Ga-PSMA PET/CT showed significantly higher sensitivity and accuracy than BS (96.2% vs. 73.1%, and 99.1% vs. 84.1%) for the detection of skeletal lesions. For extraskeletal lesions, 68Ga-PSMA PET/CT showed an additional 96 unexpected lesions with a median standardized uptake value of 17.6. Conclusion 68Ga-PSMA PET/CT is superior to and can potentially replace bone scan in the evaluation for skeletal metastases in the clinical and trial setting because of its ability to detect lytic and bone marrow metastases.

Grants from the Research Foundation FWO (Flanders) and NRF (South-Africa) (Grant No. G0G7617N) to Liesa Tack and from the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen) to Frederick Verbeke (Grant No. 131356).

Objective To compare the diagnostic accuracy of Ga-prostate-specific membrane antigen (PSMA)-HBED-CC PET/computed tomography (CT) imaging for the detection of androgen-dependent recurrent prostate carcinoma (ADPC) in Black South Africans (BSAs) versus White South Africans (WSAs) with increasing serum prostate-specific antigen (PSA) values below or equal to 10 ng/ml. Patients and methods A total of 61 patients with ADPC were prospectively included in the study (mean age: 66.7 years): 38 WSAs and 23 BSAs. Ga-PSMA-HBED-CC PET/CT imaging results obtained were related to serum PSA levels and to ethnicity. Results A total of 41 (67%) patients had a positive Ga-PSMA-HBED-CC scan result. Ga-PSMA-HBED-CC PET/CT positivity was significantly higher in patients with PSA values more than 2 ng/ml [32/38 (84%) patients] when compared with patients with PSA values less than 0.5 ng/ml [6/11 (55%) patients] or PSA values of 0.5-2 ng/ml [3/12 (25%) patients] (P=0.0001). Mean PSA values proved not significantly different in patients presenting with extrapelvic involvement when compared with those with intrapelvic involvement or between patients who presented with bone involvement versus those who did not on Ga-PSMA-HBED-CC PET/CT) (P≥0.147). Age, Gleason-scores, median PSA values, the frequency of a positive scan result, the frequency of bone involvement, and extrapelvic involvement proved similar in WSAs and BSAs (P≥0.417). Conclusion Ga-PSMA-HBED-CC PET/CT imaging identified a recurrence in 67% of the patients under study. Higher PSA levels were associated with Ga-PSMA-HBED-CC PET/CT positivity and the detection rate. Imaging results obtained proved similar in BSAs and WSAs, suggesting that the tumor burden and growth rate of ADPC are similar in both races.

Purpose The incidence of prostate cancer is 60% higher and the mortality rate is two- to three-times greater in black versus white men. We report on differences in 68Ga-PSMA-11 PET/CT imaging findings in 77 black South-African (BSAs) and 18 white South-African (WSAs) treatment-naïve primary prostate carcinoma (PPC) patients. Methods 68Ga-PSMA-11 PET/CT imaging findings were compared to histological, biochemical and morphological imaging data. Patients were grouped into three Gleason grade groups (GG), GG 1 (scores 3 + 3 and 3 + 4), GG2 (scores 4 + 3 and 4 + 4) and GG3 (scores 9 and 10), and the PSA difference among the groups was determined. Inter-racial difference in SUVmax of the primary tumor as well as its correlation with serum PSA were also determined. Results Ninety-three out of 95 PPC where readily identified on 68Ga-PSMA-11 PET/CT imaging. Median PPC SUVmax and serum PSA values proved significantly higher (p = 0.033 and p = 0.003) in GG3 patients (median 16.4 and 180 ng/ml) when compared to GG1 patients (median 9.6 and 25.1 ng/ml) or GG2 patients (median 8.8 and 46.2 ng/ml). SUVmax significantly correlated with serum PSA-values (r = 0.377 (p = 0.0001)). Age, frequency of lymph node involvement and distant metastases, and GGs (p ≥ 0.153) were similar in BSAs and WSAs, both median serum PSA-values as well as SUVmax values proved significantly higher in BSAs when compared to WSAs, respectively, 81.6 ng/ml versus 14.5 ng/ml (p = 0.0001) and 11.9 versus 4.38 (p = 0.004). Moreover, Gleason-score normalized median SUVmax values proved 2.5 times higher in BSAs when compared to WSAs (p = 0.005). Conclusion SUVmax values proved significantly related to GG and to be significantly higher in BSAs when compared to WSAs. Also, SUVmax significantly correlated with serum PSA values, which was significantly higher in BSAs when compared with WSAs.

Metastatic prostate carcinoma overexpresses prostate-specific membrane antigen (PSMA), making this antigen a suitable target for radioligand therapy of the disease. Here we report on our experience with a series of 73 castration-resistant prostate carcinoma patients treated with

BACKGROUND: Tuberculosis remains an important cause of morbidity and mortality worldwide, the diagnosis, staging and treatment response evaluation of which remains sub-optimal. We evaluated PET/CT imaging with a novel tracer, 68Ga-citrate, in this setting. METHODS: Thirteen patients with tuberculosis underwent PET/CT imaging with 68Ga-citrate. Tuberculosis was diagnosed with bacteriological or histopathology studies (N.=8) or based on a combination of clinical data, biochemistry and imaging (N.=5). PET images were analyzed qualitatively and semi-quantitatively and compared to CT findings. RESULTS: All 13 patients demonstrated abnormal tracer accumulation in the lungs or extra-pulmonary or both. 68Ga-citrate accumulated in every lung lesion noted on CT in six cases (46%). In seven cases (54%) some of the lung lesions noted on CT were not 68Ga-citrate avid, which is suggestive of non-active tuberculous lesions. Ten patients (77%) demonstrated extrapulmonary involvement, which included various lymph node groups, skeletal lesions, pleural-, splenic- and gastrointestinal tract involvement. Detection of extra-pulmonary involvement was higher on PET compared to CT (more lesions detected) in eight cases (80%). CONCLUSIONS: 68Ga-citrate PET accumulates in both pulmonary and extra-pulmonary tuberculous lesions and may provide a way of distinguishing active from inactive lesions for treatment response evaluation. 68Ga-citrate PET may be superior to CT in the detection of extrapulmonary involvement. ispartof: Quarterly Journal of Nuclear Medicine and Molecular Imaging vol:63 issue:1 pages:48-55 ispartof: location:Italy status: published

Background To report on imaging findings using 68Ga-PSMA-HBED-CC PET in a series of 19 breast carcinoma patients. Methods 68Ga-PSMA-HBED-CC PET imaging results obtained were compared to routinely performed staging examinations and analyzed as to lesion location and progesterone receptor status. Results Out of 81 tumor lesions identified, 84% were identified on 68Ga-PSMA-HBED-CC PET. 68Ga-PSMA-HBED-CC SUVmean values of distant metastases proved significantly higher (mean, 6.86, SD, 5.68) when compared to those of primary or local recurrences (mean, 2.45, SD, 2.55, p = 0.04) or involved lymph nodes (mean, 3.18, SD, 1.79, p = 0.011). SUVmean values of progesterone receptor-positive lesions proved not significantly different from progesterone receptor-negative lesions. SUV values derived from FDG PET/CT, available in seven patients, and 68Ga-PSMA-HBED-CC PET/CT imaging proved weakly correlated (r = 0.407, p = 0.015). Conclusions 68Ga-PSMA-HBED-CC PET/CT imaging in breast carcinoma confirms the reported considerable variation of PSMA expression on human solid tumors using immunohistochemistry.

The relationship between tumor metabolism and stage, subcutaneous and visceral fat thickness, and their glucose metabolism and overall survival in patients recently diagnosed with pancreatic carcinoma was assessed.Thirty-eight consecutive patients were studied. Subcutaneous fat thickness (SFT), visceral fat thickness (VFT), and their corresponding FDG SUVmean, as well as SUVmean and SUVmax values of the primary tumor (PT) were derived from FDG-PET CT imaging. Results obtained as well as clinical variables obtained, including gender and BMI, were related to patient outcome. Median follow-up was 382 days (range: 36-917 days).Median age was 66 years (13 women). Mean BMI was 24.6 (SD: 4.5). Lymph node (LN) involvement was diagnosed in 17 patients and 14 patients presented with distant metastases. Mean SUV max and SUVmean values of the PT were 9.0 (SD 5.9) and 4.2 (SD 2.1). Mean values of SFT and VFT were, respectively, 11.9 mm (range 1-31.7 mm) and 11.5 mm (range 0-49.8 mm). The corresponding SUVmean values were 0.4 (range 0-1.0) and 0.6 (range 0.0-1.6). SUVmean values of SFT proved significantly lower in LNpositive versus LNnegative patients (p = 0.021), in patients with and without metastatic disease (p = 0.017) and in stage III+IV patients versus stage I+II patients (p = 0.03). An inverse logarithmic relationship was found between SUVmean values of subcutaneous fat and SUVmean values of the PT (p = 0.02). Only disease stage dichotomized according to stage I+IIA versus stage IIB+III+IV was predictive of overall survival (p = 0.05).Glucose metabolism of subcutaneous fat in de novo diagnosed pancreas carcinoma patients presenting with lymph node involvement and metastatic disease is significantly reduced and inversely correlated to the primary tumor metabolism. Of the various fat-related variables studied, none proved significantly related to outcome.

The process of inflammation (with or without infection) forms part of essentially every major debilitating disease. Early detection and accurate distinction of inflammation from infection are important to optimize and individualize therapy. Nuclear medicine is ideally suited for the detection of pathologic changes early on and is able to target a magnitude of role players involved in the aforementioned processes. Hybrid modalities such as PET/CT and PET/MRI offer high spatial resolution that combines morphologic and pathophysiological changes and add various quantification possibilities that are preferable in these settings. It follows then that the development of PET radiopharmaceuticals is imperative to make use of these latest advances. Gallium-68 (Ga-68)-based tracers are exceptionally well suited to these indications, considering the year-round availability from a single generator, the relative cost-effectiveness, and relative ease of labeling. Over the past few years, the development of Ga-68-based tracers has understandably exploded with a recent growing interest in infection and inflammation imaging. This review aims to highlight some of the most important and interesting advances made with Ga-68-based PET/CT in the field of infection and inflammation imaging.

The purpose of this study was to determine patients' lean body mass (LBM) and lean tissue (LT) mass using a computed tomography (CT)-based method, and to compare standardized uptake value (SUV) normalized by these parameters to conventionally normalized SUVs. Head-to-toe positron emission tomography (PET)/CT examinations were retrospectively retrieved and semi-automatically segmented into tissue types based on thresholding of CT Hounsfield units (HU). The following HU ranges were used for determination of CT-estimated LBM and LT (LBMCT and LTCT): -180 to -7 for adipose tissue (AT), -6 to 142 for LT, and 143 to 3010 for bone tissue (BT). Formula-estimated LBMs were calculated using formulas of James (1976 Research on Obesity: a Report of the DHSS/MRC Group (London: HMSO)) and Janmahasatian et al (2005 Clin. Pharmacokinet. 44 1051-65), and body surface area (BSA) was calculated using the DuBois formula (Dubois and Dubois 1989 Nutrition 5 303-11). The CT segmentation method was validated by comparing total patient body weight (BW) to CT-estimated BW (BWCT). LBMCT was compared to formula-based estimates (LBMJames and LBMJanma). SUVs in two healthy reference tissues, liver and mediastinum, were normalized for the aforementioned parameters and compared to each other in terms of variability and dependence on normalization factors and BW. Comparison of actual BW to BWCT shows a non-significant difference of 0.8 kg. LBMJames estimates are significantly higher than LBMJanma with differences of 4.7 kg for female and 1.0 kg for male patients. Formula-based LBM estimates do not significantly differ from LBMCT, neither for men nor for women. The coefficient of variation (CV) of SUV normalized for LBMJames (SUVLBM-James) (12.3%) was significantly reduced in liver compared to SUVBW (15.4%). All SUV variances in mediastinum were significantly reduced (CVs were 11.1-12.2%) compared to SUVBW (15.5%), except SUVBSA (15.2%). Only SUVBW and SUVLBM-James show independence from normalization factors. LBMJames seems to be the only advantageous SUV normalization. No advantage of other SUV normalizations over BW could be demonstrated.

In PET/CT, quantitative evaluation of tumour metabolic activity is possible through standardized uptake values, usually normalized for body weight (BW) or lean body mass (LBM). Patient-specific LBM can be estimated from whole-body (WB) CT images. As most clinical indications only warrant PET/CT examinations covering head to midthigh, the aim of this study was to develop a simple and reliable method to estimate LBM from limited-coverage (LC) CT images and test its validity.Head-to-toe PET/CT examinations were retrospectively retrieved and semiautomatically segmented into tissue types based on thresholding of CT Hounsfield units. LC was obtained by omitting image slices. Image segmentation was validated on the WB CT examinations by comparing CT-estimated BW with actual BW, and LBM estimated from LC images were compared with LBM estimated from WB images. A direct method and an indirect method were developed and validated on an independent data set.Comparing LBM estimated from LC examinations with estimates from WB examinations (LBMWB) showed a significant but limited bias of 1.2 kg (direct method) and nonsignificant bias of 0.05 kg (indirect method).This study demonstrates that LBM can be estimated from LC CT images with no significant difference from LBMWB.

Tuberculosis (TB) is currently the world's leading cause of infectious mortality. Imaging plays an important role in the management of this disease. The complex immune response of the human body to Mycobacterium tuberculosis results in a wide array of clinical manifestations, making clinical and radiological diagnosis challenging. F-18-FDG-PET/CT is very sensitive in the early detection of TB in most parts of the body; however, the lack of specificity is a major limitation. F-18-FDG-PET/CT images the whole body and provides a pre-therapeutic metabolic map of the infection, enabling clinicians to accurately assess the burden of disease. It enables the most appropriate site of biopsy to be selected, stages the infection, and detects disease in previously unknown sites.F-18-FDG-PET/CT has recently been shown to be able to identify a subset of patients with latent TB infection who have subclinical disease. Lung inflammation as detected by F-18-FDG-PET/CT has shown promising signs that it may be a useful predictor of progression from latent to active infection. A number of studies have identified imaging features that might improve the specificity of F-18-FDG-PET/CT at some sites of extrapulmonary TB. Other PET tracers have also been investigated for their use in TB, with some promising results. The potential role and future perspectives of PET/CT in imaging TB is considered. Literature abounds on the very important role of F-18-FDG-PET/CT in assessing therapy response in TB. The use of F-18-FDG for monitoring response to treatment is addressed in a separate review. (C) 2017 Elsevier Inc. All rights reserved.

The aim of this retrospective study was to evaluate the accuracy of bone SPECT (single photon emission computed tomography)/CT (computed tomography) in diagnosing loosening of fixation material in patients with recurrent or persistent back pain that underwent lumbar arthrodesis with pedicle screws using surgery and clinical follow-up as gold standardA total of 48 patients (median age 49 years, range 21-81 years; 17 men) who had undergone lumbar spinal arthrodesis were included in this retrospective analysis. SPECT/CT results were compared to the gold standard of surgical evaluation or clinical follow-up. Positive SPECT/CT results were considered true positives if findings were confirmed by surgery or if clinical and other examinations were completely consistent with the positive SPECT/CT finding. They were considered false positives if surgical evaluation did not find any loose pedicle screws or if symptoms subsided with non-surgical therapy. Negative SPECT/CT scans were considered true negatives if symptoms either improved without surgical intervention or remained stable over a minimum follow-up period of 6 months. Negative SPECT/CT scans were determined to be false negatives if surgery was still required and loosening of material was found.The median length of time from primary surgery to bone SPECT/CT referral was 29.5 months (range 12-192 months). Median follow-up was 18 months (range 6-57) for subjects who did not undergo surgery. Thirteen of the 48 patients were found to be positive for loosening on bone SPECT/CT. Surgical evaluation (8 patients) and clinical follow-up (5 patients) showed that bone SPECT/CT correctly predicted loosening in 9 of 13 patients, while it falsely diagnosed loosening in 4 patients. Of 35 negative bone SPECT/CT scans, 12 were surgically confirmed. In 18 patients, bone SPECT/CT revealed lesions that could provide an alternative explanation for the symptoms of pain (active facet degeneration in 14 patients, and disc and sacroiliac osteodegeneration in 7 patients and 1 patient, respectively). Overall sensitivity and specificity for the detection of loosening were 100 % and 89.7 %, respectively. The positive and negative predictive values were 69 % and 100 %, respectively.This retrospective analysis suggests that bone SPECT/CT bone is a highly sensitive and specific tool for the exclusion of screw loosening in patients who present with recurrent low back pain after having undergone lumbar arthrodesis. In addition, it can identify other potential causes of recurrent low back pain in this patient population.

The case of a 49-year-old transgender individual with a history of bilateral silicone breast implants and a right lung mass proven by biopsy to be a non-small cell lung cancer is presented. In addition to the primary malignancy, a positron emission tomography/computed tomography scan showed contralateral hypermetabolic adenopathy in the left axilla that was suggestive of nodal metastatic disease. Additional imaging and histological examination of the lymph nodes indicated silicone breast implant leakage and silicone adenitis as the underlying cause of the hypermetabolic axillary lymph node.

Chemical modifications on protein biopharmaceuticals introduce extra variability in addition to their inherent complexity, hence require more comprehensive analytical and functional characterization during their discovery, development, and manufacturing. Somatropin (i.e., recombinant human growth hormone, rhGH) modified with the chelating agent S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) allows the incorporation of radiometals for research and possible theranostic purposes. We previously demonstrated that this conjugation leads to multiple substitution degrees and positional isomers within the product. In vitro techniques at the molecular and cellular levels were now applied to assess their functional quality: (i) size exclusion chromatography (SEC) demonstrated functional complexation with human growth hormone binding protein (hGHBp) to the different NOTA-modified somatropins as well as to gallium chelated NOTA-functionalities (Ga-10:1 NOTA-somatropin); (ii) native mass spectrometry (MS) offered in-depth information, a substitution degree up to four NOTAs was still functional; (iii) circular dichroism (CD) analysis confirmed the complexation of unmodified and NOTA-modified somatropin to hGHBp; and (iv) a hGHR bioassay demonstrated initiation of the signal transduction cascade, after binding of all investigated products to the receptor presented on cells with a similar potency (pEC

In approximately 10-30% of patients presenting with angina complaints, normal or non-obstructive coronary arteries are found on angiography. In this review paper, available literature on the underlying pathophysiological substrate explaining these discrepancies is reviewed. Both histological studies as well as studies using intravascular ultrasound e.g. the PROSPECT trial, show that epicardial coronary vessel significant lumen stenosis may be delayed until a plaque occupies 40% of the internal elastic lamina area. Limited available data suggest that these angiographically undetectable plaques are associated with an abnormal vasodilation capacity of the coronary circulation and may results in reversible perfusion defects on myocardial perfusion imaging (MPI). Organic non-atherosclerotic causes of epicardial coronary artery disease such as anomalous coronary arteries that course between the aorta and pulmonary artery, myocardial bridging and coronary vasospasm may also contribute to MPI results suggesting the presence of ischemia in the presence of normal coronary arteries on coronary angiography. Additional causes of reversible perfusion defects on MPI in the presence of a normal coronary angiogram are intraventricular conduction disturbances. The existence of reversible perfusion defects in the anteroseptal region in most of the patients suffering from left bundle branch block (LBBB) on MPI following physical exercise as stressor is well documented. As the observed reduced septal uptake of both 201Tl and 99mTc-sestamibi/tetrofosmin in LBBB reflects coronary autoregulation in response to lower oxygen demands, not surprisingly, dipyridamole which uniformly exploits flow reserve, has proven more accurate for the diagnosis of coronary artery disease (CAD) in patients suffering from LBBB. Although patients with a permanent ventricular pacemaker have a similar conduction abnormality as patients presenting with a LBBB, most of the defects found on MPI imaging in this patient population (in up to 78% of patients with a normal coronary angiogram that area continuously paced) are localized in the inferoposterior (71%), apical (50%) and inferoseptal (28%) wall; coronary flow velocities in the left anterior descending (LAD) and dominant coronary artery and coronary flow reserve are also significantly lower when compared to a control group. Contrary to what is seen in LBBB patients, dipyridamole stress does not significantly reduce the incidence of abnormalities found but limits the defects to the inferior wall. Furthermore, the frequency of abnormalities found on MPI increases over time with right ventricular outflow tract pacing. Previous histologic studies have shown that microvessel disease is often accompanied by a slow-flow phenomenon reflecting decreased resting flow velocity. Thus, not surprisingly, MPI reversible abnormalities in the presence of a normal coronary angiogram have been reported in a wide variety of diseases characterized by microvessel disease such as diabetes, systemic lupus erythematosus, Behcet's disease and metabolic syndrome. In these patients, low adiponectin and high lipoprotein(a) levels are found which are known to be associated with endothelial dysfunction, atherosclerosis and coronary artery disease. Furthermore, in these patients, limited available data suggest that reversible perfusion defects on MPI confer a significantly poorer prognosis both in terms of hard event rate (MI and cardiac death) and total event rate (MI, cardiac death or late revascularization). It is thus suggested that MPI could discriminate patients with a more severe prognosis. Finally, physical training in patients with primary microvascular angina appears to be associated with reduction of myocardial perfusion abnormalities.

In this paper, data available on nuclear medicine imaging using commercially available radiopharmaceuticals for the differentiation, staging, and prediction or assessment of the response to treatment in tuberculosis (TB) are reviewed. Limited available studies suggest that single photon emission computed tomography (SPECT) using either 201Tl, 99mTc-sestamibi, or 99mTc-tetrofosmin is accurate (≥85%) and has a high negative predictive value (≥90%) for the differentiation of TB from carcinoma in patients presenting with a solitary pulmonary nodule (SPN). The criteria for detection of TB on 201Tl SPECT are nondepiction of the suspicious lesion in the delayed image or a negative retention index [washout on the delayed images (3–4 h postinjection) vs. the early image (5–15 min postinjection)] and a comparable-to-background uptake on 99mTc-sestamibi or 99mTc-tetrofosmin SPECT. Another SPECT tracer of potential interest for the differentiation of TB from malignant SPN that warrants further exploration, is N-isopropyl-p-[123I]iodoamphetamine (123I-IMP). In contrast, 18F-fluorodeoxyglucose (18F-FDG) PET is unable to differentiate malignancy from TB and thus cannot be used as a tool to reduce futile biopsy/thoracotomy in these patients. A limited number of studies have reported on the potential of nuclear medicine imaging in assessment of the extent of disease in patients with extrapulmonary TB using 67Ga-citrate SPECT and 18F-FDG PET, respectively. 67Ga-citrate SPECT was shown to be as sensitive as bone scintigraphy for the detection of bone infection and was found to be complementary to computed tomography (CT) imaging. 18F-FDG PET was found to be significantly more efficient when compared with CT, respectively, in over half of patients for the identification of sites of lymph node involvement that were missed by CT and often the only sites of extrapulmonary TB identified. Unfortunately, 18F-FDG PET findings did not lead to alterations in treatment planning in any of the patients under study. Additional studies confirming these findings are urgently required. Similar to the setting of SPN, 18F-FDG PET cannot differentiate malignant lymph node involvement from lymph node involvement by TB. These results and the recent findings of Demura and colleagues using 18F-FDG PET further suggest that nuclear medicine imaging techniques could be used for the evaluation of therapeutic response. Prospective studies, focusing on specific subgroups of patients in whom such an imaging approach might be clinically relevant, for example in multidrug-resistant TB patients, are warranted. In acquired immunodeficiency syndrome patients, 67Ga scintigraphy proved to be a reliable and sensitive method for the primary detection and follow-up of opportunistic pneumonias, including TB. Combining 201Tl scintigraphy with 67Ga scintigraphy was shown to increase the specificity for both pulmonary and extrapulmonary TB, which is a 67Ga(+) and 201Tl(-) mismatch pattern in acquired immunodeficiency syndrome patients that is specific for mycobacterial infections. Finally, the results obtained using both SPECT and PET indicate that nuclear medicine could be an important noninvasive method for the determination of disease activity, detection of extrapulmonary TB, and determination of response to therapy.

No data is available on the different FDG PET and CT findings in the lymph nodes (LN) of patients with HIV and tuberculosis (TB) who respond compared with those who do not respond to anti-TB treatment by 4 months after initiation of TB treatment. These findings were the focus of our study. PET/CT scans performed at 4 months after initiation of TB treatment in 20 consecutive HIV patients were analysed. SUVmax values were obtained for all regions of LN involvement. The diameter of the LNs was measured and the CT enhancement (LNs showing peripheral rim enhancement with central low attenuation, PRECLO, in comparison with homogeneously involved LNs) and the calcification patterns of involved LNs assessed. The relationship between the PET and CT findings and the clinical outcome, response or nonresponse, was evaluated. FDG PET identified 91 sites of LN involvement, 20 of which were not identified by CT. SUVmax values were significantly higher in nonresponders (8 patients, SUVmax 11.2 ± 4.0, mean ± SD) when compared to responders (12 patients, SUVmax 2.6 ± 2.3; p = 0.0001). In ROC analysis (AUC 0.952) a cut-off value of 4.5 for SUVmax yielded a sensitivity and specificity of 95 % and 85 % for discriminating nonresponding from responding LNs. LNs were significantly larger in nonresponders (1.9 ± 0.4 cm) than in responders (1.4 ± 0.4 cm; p = 0.0001); the AUC in the ROC analysis was 0.76. PRECLO LNs were significantly larger (2.2 ± 0.3 cm) than homogeneous involved LN basins (1.5 ± 0.4 cm) and LN basins with calcification (1.4 ± 0.5 cm; p = 0.001). Using the presence of at least one LN basin with PRECLO as a criterion for nonresponse, responders could be separated from nonresponders with a sensitivity of 88 % and a specificity of 66 %. LNs responding to TB treatment could be differentiated from nonresponding LNs with a sensitivity and specificity of 95 % and 85 % using a SUVmax cut-off value of 4.5 and a sensitivity and specificity of 88 % and 66 % using the presence of at least one LN basin with PRECLO.

Objective To evaluate differences in glucose uptake by skeletal muscle tissue and subcutaneous fat in HIV patients on highly active antiretroviral therapy (HAART) presenting with and without lipodystrophy as well as in drug-naive HIV patients using F-fluorodeoxyglucose (FDG) positron emission tomography. Patients and methods Thirty-nine consecutive patients suffering from HIV: seven drug-naive patients, 21 nonlipodystrophic patients on HAART and 11 patients on HAART, respectively, suffering from lipodystrophy were prospectively included. All patients underwent a whole-body FDG positron emission tomography examination. Standardized uptake values (SUV values) of muscle and subcutaneous fat were compared and related to demographic and biochemical variables. Results SUV mean values of subcutaneous fat were significantly higher in patients under HAART presenting with lipodystrophy when compared with untreated and treated, nonlipodystrophic patients (P=0.000). SUV mean values of subcutaneous fat significantly correlated with treatment duration (r=0.56, P=0.000) and CD4 count (r=0.51, P=0.001) and inversely correlated with viral load (r=-0.61, P=0.000). Finally, SUV mean values of thigh muscles were not significantly different between the three different patient groups under study. Conclusion Quantitative FDG uptake by subcutaneous fat proved significantly higher in HIV patients under HAART presenting with lipodystrophy. HAART did not influence FDG uptake by human skeletal muscle tissue under basal conditions.

Background Locoregional lymph node metastasis is an important prognostic factor in patients with bladder cancer. Multimodal treatment, depending on preoperative stage, may improve survival. The standard imaging modalities for staging (computed tomography [CT] or magnetic resonance imaging [MRI]) have an accuracy range of 70–90% for lymph node staging. A more accurate preoperative diagnostic test could improve survival rates even more. Objective To determine whether the use of 2-deoxy-2 [F] fluoro-D-glucose (FDG) positron emission tomography (PET) in combination with CT (FDG-PET/CT) can increase the reliability of preoperative lymph node staging in patients with nonmetastatic invasive bladder cancer (T2 or higher, M0) or recurrent high-risk superficial disease (T1G3 with or without Tis, M0). Design, setting, and participants Fifty-one patients underwent a preoperative FDG-PET/CT between April 2004 and December 2007. Independent of the result for lymph node status, all patients underwent a radical cystectomy and an extended lymphadenectomy. The FDG-PET/CT and CT results were compared with the definitive pathologic results. Measurements Among the 51 patients, 13 patients had metastatically involved locoregional lymph nodes, diagnosed on histopathology. In six patients, these nodes demonstrated increased FDG uptake on PET. In seven patients, PET/CT did not diagnose the positive lymph nodes. PET/CT was false positive in one patient. Results and limitations For the diagnosis of node-positive disease, the accuracy, the sensitivity, and the specificity of FDG-PET/CT were 84%, 46%, and 97%, respectively. When analysing the results of CT alone, there was accuracy of 80%, sensitivity of 46%, and specificity of 92%. The use of FDG-PET/CT is hampered by technical limitations. Conclusions We found no advantage for combined FDG-PET/CT over CT alone for lymph node staging of invasive bladder cancer or recurrent high-risk superficial disease.

To assess prospectively the relationship between fluorodeoxyglucose uptake by lymph nodes, the number of sites of lymph node involvement and cluster of differentiation 4 (CD4) cell count. An inverse relationship, if existing, between these variables would provide indirect support for the concept of homing induced apoptosis.We evaluated the intensity and extent of fluorodeoxyglucose uptake in lymph nodes of HIV patients under antiviral treatment by means of PET imaging. Quantitative results obtained were related to CD4 cell count and viral loads. Correlation analysis was performed using a nonparametric test and correction for multiple comparisons.Predominant sites of lymph node involvement were the cervical and axillary regions, followed by the inguinal region. CD4 cell count was inversely correlated to the average of the averaged standardized uptake values (SUV) of involved lymph nodes and to the number of sites of lymph node involvement. Viral load was positively correlated to the average of the averaged SUV-mean values of involved lymph nodes and also to the number of sites of lymph nodes involved. An inverse correlation between CD4 cell count and viral load was identified.The inverse relationship between CD4 cell count and the average of the averaged SUV-mean values of involved lymph nodes and between CD4 cell count and the number of sites of lymph node involvement observed, indirectly supports the theory of CD4 cell depletion through forced lymph node homing.

This paper reviews currently available PET studies performed either to improve our understanding of the pathogenesis of HIV-1 infection or to assess the value of PET imaging in the clinical decision making of patients infected with HIV-1 presenting with AIDS-related opportunistic infections and malignancies. FDG PET has shown that HIV-1 infection progresses by distinct anatomical steps, with involvement of the upper torso preceding involvement of the lower part of the torso, and that the degree of FDG uptake relates to viral load. The former finding suggests that lymphoid tissues are engaged in a predictable sequence and that diffusible mediators of activation might be important targets for vaccine or therapeutic intervention strategies. In lipodystrophic HIV-infected patients, limited available data support the hypothesis that stavudine-related lipodystrophy is associated with increased glucose uptake by adipose tissue as a result of the metabolic stress of adipose tissue in response to highly active antiretroviral treatment (HAART). Finally, in early AIDS-related dementia complex (ADC), striatal hypermetabolism is observed, whereas progressive ADC is characterized by a decrease in subcortical and cortical metabolism. In the clinical setting, PET has been shown to allow the differentiation of AIDS-related opportunistic infections and malignancies, and to allow monitoring of side effects of HAART. However, in patients suffering from HIV infection and presenting with extracerebral lymphoma or other human malignancies, knowledge of viraemia is essential when interpreting FDG PET imaging.

To investigate dynamic ictal perfusion changes during temporal lobe epilepsy (TLE).We investigated 37 patients with TLE by ictal and interictal SPECT. All ictal injections were performed within 60 s of seizure onset. Statistical parametric mapping was used to analyse brain perfusion changes and temporal relationships with injection time and seizure duration as covariates.The analysis revealed significant ictal hyperperfusion in the ipsilateral temporal lobe extending to subcortical regions. Hypoperfusion was observed in large extratemporal areas. There were also significant dynamic changes in several extratemporal regions: ipsilateral orbitofrontal and bilateral superior frontal gyri and the contralateral cerebellum and ipsilateral striatum.The study demonstrated early dynamic perfusion changes in extratemporal regions probably involved in both propagation of epileptic activity and initiation of inhibitory mechanisms.

The aim of this study was to report on the feasibility and accuracy of spleen volume determination on FDG PET/CT imaging using region growing and the CT part of the PET/CT examination as anatomical landmark (PET-CT based spleen volume method PBM) and volume summation of axial CT sections of the spleen as gold standard (true spleen volume (TSV). We also aimed to compare results obtained to the estimative methods (ESV).Thirty-nine FDG PET/CT images taken from 32 patients (15 women, age range: 16-83 years) suffering from lymphoma, covering a wide range of spleen volumes based on visual CT assessment, in whom CT as well as FDG PET images revealed no focal spleen abnormalities were included for analysis. ESV1, ESV2 and PBM were determined on all examinations and compared to TSV.ESV1 volumes were significantly larger (median 668 cm3 [range: 121-4303 cm3] [P=0.0001]) and ESV2 volumes significantly smaller (median 424 cm3 [range: 84-2679 cm3] [P=0.0001]) when compared to TSV volumes (median 582 cm3 [range: 105-4847 cm3] which was not so for PBS volumes (median 540cm3 [range: 120-4560 cm3]). Time needed for TSV assessment (median: 17 min. [range: 6-65 min.]) was related to spleen volume (r=0.691 [P=0.0001]). The mean and standard deviation of the percentage spread (ESV1, ESV2, PBM-TSV/100%) around the mean (ESV1, ESV2, PBM+TSV/2) were respectively 18%±15.6% (ESV1 vs. TSV), -25%±15.6% (ESV2 vs. TSV) and -2.8%±12.3% (PBM vs. TSV). Mean SUVmax of the spleen was 4.8 SUV (SD: 2.6 SUV), mean percentage cut-off for region growing was 7.3% (sd: 5.8%). Spleen volumes defined by PBM correlated with their corresponding SUVmax value (r=0.469 [P=0.03]). Time needed for PBM measurements was between 2-3 min in all patients.Spleen volumes may be rapidly and accurately derived from the FDG PET part of the PET/CT examination through region growing and by using the CT part of the PET/CT examination as anatomical landmark for contour delineation. As opposed to ESV1 and ESV2, the PBM method does not suffer from a systematic bias and shows a smaller variation against the mean percentage difference. Combining functional and morphological data for spleen volume assessment is time-saving.

The aim of this study was to determine and validate a set of Hounsfield unit (HU) ranges to segment computed tomography (CT) images into tissue types and to test the validity of dual-energy X-ray absorptiometry (DXA) tissue segmentation on pure, unmixed porcine tissues.This preclinical prospective study was approved by the local ethical committee. Different quantities of porcine bone tissue (BT), lean tissue (LT) and adipose tissue (AT) were scanned using DXA and CT. Tissue type segmentation in DXA was performed via the standard clinical protocol and in CT through different sets of HU ranges. Percent coefficients of variation (%CV) were used to assess precision while % differences of observed masses were tested against zero using the Wilcoxon signed-rank Test.Total mass DXA measurements differ little but significantly (P=0.016) from true mass, while total mass CT measurements based on literature values show non-significant (P=0.69) differences of 1.7% and 2.0%. BT mass estimates with DXA differed more from true mass (median -78.2 to -75.8%) than other tissue types (median -11.3 to -8.1%). Tissue mass estimates with CT and literature HU ranges showed small differences from true mass for every tissue type (median -10.4 to 8.8%).The most suited method for automated tissue segmentation is CT and can become a valuable tool in quantitative nuclear medicine.

With the routine use of 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) scans, metabolic activity of tumors can be quantitatively assessed through calculation of SUVs. One possible normalization parameter for the standardized uptake value (SUV) is lean body mass (LBM), which is generally calculated through predictive equations based on height and body weight. (Semi-)direct measurements of LBM could provide more accurate results in cancer populations than predictive equations based on healthy populations. In this context, four methods to determine LBM are reviewed: bioelectrical impedance analysis, dual-energy X-ray absorptiometry. CT, and magnetic resonance imaging. These methods were selected based on clinical accessibility and are compared in terms of methodology, precision and accuracy. By assessing each method's specific advantages and limitations, a well-considered choice of method can hopefully lead to more accurate SUVLBM values, hence more accurate quantitative assessment of 18F-FDG PET images.

OBJECTIVE:. Because of the irreversibility of lesioning procedures and their possible side effects, we studied the efficacy of replacing bilateral anterior capsulotomy with chronic electrical capsular stimulation in patients with severe, long-standing treatment-resistant obsessive-compulsive disorder. METHODS: We-stereotactically implanted quadripolar electrodes in both anterior limbs of the internal capsules into six patients with severe obsessive-compulsive disorder. Psychiatrists and psychologists performed a double-blind clinical assessment. A blinded random crossover design was used to assess four of those patients, who underwent continuous stimulation thereafter. RESULTS: The psychiatrist-rated Yale-Brown Obsessive Compulsive Scale score was lower in the stimulation-on condition (mean, 19.8 +/- 8.0) than in the postoperative stimulator-off condition (mean, 32.3 +/- 3.9), and, this stimulation-induced effect was maintained for at least 21 months' after surgery. The Clinical Global Severity. score decreased from 5 (severe; standard deviation, 0) in the stimulation-off condition (moderate to moderate-severe; standard deviation, 0.96) in the stimulation-on condition. The Clinical Global Improvement scores were unchanged in one patient and much improved in the other three during Stimulation. During the stimulation-off period, symptom severity approached baseline levels in the four patients. Bilateral stimulation led to increased signal on functional magnetic resonance imaging studies,, especially in the pons. Digital subtraction analysis of preoperative [F-18]2-fluoro-2-deoxy-D-glucose positron emission tomographic scans and positron emission tomographic scans obtained after 3 months of stimulation showed decreased frontal metabolism during stimulation. CONCLUSION: These observations indicate that capsular stimulation reduces,core symptoms 21 months after surgery in patients severe, long-standing, treatment in patients wit refractory obsessive-compulsive disorder. The stimulation elicited changes in regional brain activity as measured by functional magnetic resonance imaging and positron emission tomography.

PURPOSE: We describe a method for analysis of [ 11 C]flumazenil data using an input curve directly derived from the positron emission tomography (PET) images. PROCEDURE: The shape of the tracer plasma curve was obtained from the product of the intact flumazenil fraction in plasma in six arterial samples and the internal carotid artery time-activity curve (TAC). The resulting curve was calibrated using the [ 11 C]flumazenil concentration in three of the six samples. The curve peak was recovered by adding an exponential function to the scaled curve whose parameters were estimated from simultaneous fittings of several tissue TACs assuming that all regions share the same input. RESULTS: Good agreement was found between the image-derived and the experimental plasma curves in six subjects. Distribution volumes were highly correlated with linear regression slope and intercept values between [0.94, 1.03] and [−0.10, 0.16], respectively. CONCLUSION: The proposed method is suitable for benzodiazepine receptor quantification requiring only a few blood samples.

We compared the accuracy of fluorine-18 labelled 2-fluoro-2-deoxy- d-glucose positron emission tomography ((18)FDG PET) with that of technetium-99m hexamethylpropylene amine oxime leucocyte scintigraphy (LS) in the detection of infected hip prosthesis. Seventeen patients with a hip prosthesis suspected for infection were prospectively included and underwent (99m)Tc-methylene diphosphonate bone scintigraphy (BS), LS and an (18)FDG-PET scan within a 2-week period. Seven volunteers with ten asymptomatic hip prostheses were used as a control group and underwent BS and an (18)FDG-PET scan. Bacteriology of samples obtained by surgery or by needle aspiration and/or clinical follow-up for up to 6 months were used as the gold standard. Planar images of BS and LS (4 and 24 h p.i.) were acquired, followed by single-photon emission tomography (SPET) LS images (after 4 h). These images were scored as positive or negative by two experienced readers. The (18)FDG-PET scans of the patients were compared with the tracer distribution pattern in the asymptomatic control group and with BS. A phantom study was performed in order to identify artefacts. For this purpose, three different attenuation correction methods were tested. The combined analysis of the planar BS and LS resulted in a 75% sensitivity and a 78% specificity. The SPET LS images showed a better lesion contrast, resulting in an 88% sensitivity and a 100% specificity, while 24-h planar images were of no additional value. The analysis of PET images alone resulted in an 88% sensitivity and a 78% specificity. The combination of (18)FDG-PET and BS images resulted in an 88% sensitivity and a 67% specificity. Given the presence of small errors near the edge of the metal, which can induce significant artefacts in the corrected emission image, we decided to use the data without attenuation correction. In this preliminary study, (18)FDG-PET scans alone showed the same sensitivity as combined BS and LS, although the specificity was slightly lower.

In a non-surgical porcine coronary stenosis model resulting in chronic left ventricle dysfunction, we aimed in this study to evaluate the potential of magnetic resonance imaging (MRI) to distinguish dysfunctional but viable from necrotic myocardium by using multiple levels of dobutamine inotropic stimulation during a cine MRI protocol (F.P. van Rugge et al. Circulation 1994; 90: 127-138). We compared our results with histopathology. We were able to demonstrate a biphasic effect at increasing doses of dobutamine in a subgroup of animals with a high-grade coronary stenosis, while in another subgroup the coronary stenosis produced a chronic myocardial infarction, in which no functional recovery could be obtained. In this experimental protocol, dual dose dobutamine MRI proved to be an accurate and reproducible technique to perform viability studies in chronic obstructive coronary artery disease. It permits distinguishing chronic ischemic, but viable myocardium from infarcted tissue. The detection of chronically underperfused but potentially salvageable myocardium is of significant clinical importance since it may aid in determining which patients are eligible for revascularization.

In an ongoing international multi-centre trial, positron emission tomography (PET) is being used to evaluate the effect of a new P-selectin antagonist on the infarct size in patients with acute myocardial infarction, treated with thrombolysis. Although it is possible to correct for site-dependent factors, it is desirable to reduce these factors to a minimum. Therefore, acquisition and reconstruction protocols have been defined that can be closely followed by all participating centres. The resulting reconstructed images are transferred to the core centre for central processing with semi-automatic software. This paper reports on the multi-centre phantom experiment that was carried out to assess the inter-centre reproducibility of defect size determination with this protocol. Also, the spatial resolution of the short axis slices was examined. In addition, the analysis procedure was applied to normal PET studies to evaluate the specificity of perfusion defect detection. The transmural cold defect in the phantom occupied 14.8% of the left ventricular area. The automated analysis was applied to the phantom measurements from the 14 participating PET cameras. It yielded an accurate estimate of 15.1% with a standard deviation of 0.6%, indicating excellent reproducibility. The spatial resolution in the short axis slices was similar for all PET systems: 9.6+/-0.8 mm. The same procedure produced a defect size of zero in the studies of normal volunteers. This study indicates that cardiac studies from multiple PET systems can be pooled for statistical analysis.

Fluorodeoxyglucose (FDG) whole body positron emission tomography (PET) scan is increasingly used in the diagnostic work-up or follow-up of patients. In these conditions, positive PET scans with unexpected hot spots within the thyroid region could be defined as thyroid FDG-PET incidentaloma (in analogy with unexpected sonographic thyroid nodules). We describe eight consecutive patients referred to the endocrine department because of thyroid "hot spots," incidentally detected by whole body FDG-PET scan (September 1999 to March 2001). Using ultrasound, fine needle aspiration cytology (FNAC), and histology reports, we tried to identify the pathology underlying thyroid FDG-PET incidentaloma. FNAC showed an indication for surgery in all patients. Surgery has been performed in 7 patients. Malignancy was correctly identified in five patients: two medullary thyroid carcinomas, one with lymph node invasion, and three papillary thyroid carcinomas with invasion through the thyroid capsule in two of the PTC cases. In two patients with a positive FDG-PET scan, FNAC pointed to follicular neoplasms, and final histology reports showed follicular adenoma. In the remaining patient, FNAC revealed a follicular lesion, but surgery has not yet been performed. In conclusion, a small series of consecutive thyroid FDG-PET incidentaloma cases is presented and suggests a high rate of clinically relevant malignancies.

Worldwide, women account for a growing percentage of human immunodeficiency virus (HIV)–infected patients and more than half of all HIV infections. For many years, morphologic imaging methods were the main approaches employed to investigate HIV and its complications. However, during the past decade, advancements in PET and SPECT imaging technologies opened new possibilities for improved understanding of the pathophysiological processes in HIV. Diagnosis of early HIV-associated neurocognitive disorders (HAND) is important, as many of its symptoms can be caused by other conditions common to people with HIV/AIDS. Presently, there are no PET and SPECT tracers or combination of markers for HAND, hence novel HAND-specific tracers are needed if nuclear medicine is to play a role in solving the problem of the HAND "epidemic." As both highly active antiretroviral therapy (HAART)–induced lipoatrophy and cardiovascular diseases are characterized by ongoing inflammation, FDG-PET/CT imaging may represent an important imaging technique for better understanding the metabolic risk in HIV-infected women on HAART. HIV-infected women are at increased risk for the development of human papilloma virus–associated neoplasms such as cervical and anal carcinomas; these aggressive tumors could be treated better with integration of FDG-PET as part of the standard pretreatment workup. A similar value of FDG-PET may be realized in women with HIV-associated Kaposi sarcoma, as they have more extensive cutaneous disease than men do. In the era of HAART, the incidence and local invasiveness of breast cancer may change, thus creating a need to redefine the pathophysiology of breast cancer in HIV-positive women. Finally, mammary tuberculosis, occasionally the presenting symptom in HIV-infected women, may present with nonspecific clinical, radiological, and histologic findings. In these women, FDG-PET can be of value to detect the lesion for a representative biopsy, staging to exclude pulmonary and other extrapulmonary lesions, and also for therapy monitoring.

Background The aim of this study was to assess whether outcome in advanced breast cancer patients is related to metabolic response to endocrine therapy determined by fluorodeoxyglucose positron-emission tomography (FDG-PET). Methods We retrospectively identified 21 consecutive breast cancer patients receiving endocrine therapy for metastatic disease (mean number of previous therapies 3.6±3.5). All patients had been evaluated with at least 2 FDG-PETs. The first scan was performed by initiation of endocrine therapy. The second scan was performed after a mean of 3.8±1.14 months. Seventy-two FDG-avid lesions were identified and followed. The mean change in SUVmax (ΔSUVmax) was calculated per patient. Results ΔSUVmax dichotomized using the group median as cut-off (8.6%) was predictive of progression-free survival (PFS). The median PFS for the response-group (N.=10, median ΔSUVmax -20.9%) was 10.1 months. The median PFS for the progressive disease-group (N.=11, median ΔSUVmax 40.6%) was 6.7 months (log-rank testing P=0.033). Conclusions Our data suggest that breast cancer patients under hormonal therapy with stable disease on FDG-PET have a longer PFS when compared to non-responders. This finding is new, supporting the value of endocrine therapy among patients with advanced breast cancer.

We sought to determine whether PET/CT imaging with (68)Ga-citrate could be of value in distinguishing benign from malignant lung pathology in a setting with a high prevalence of granulomatous diseases.Thirty-six consecutive patients with indeterminate lung lesions prospectively underwent dual time point (60 and 120 min) (68)Ga-citrate PET/CT study prior to lung biopsy. Qualitative and semi-quantitative measures of tracer uptake in the lung lesions (SUVmax) were compared to the histopathology in order to establish an imaging pattern to distinguish benign from malignant lesions.Fourteen patients (38.9 %) were diagnosed with a malignant lesion, 12 (33.3 %) with tuberculosis (TB), and 10 participants (27.8 %) with other benign lung lesions. At 60-min post-injection, patients who were diagnosed with a malignant lesion (n = 14) demonstrated a mean SUVmax of 3.36 ± 1.14, with a median value of 3.04 (min = 1.56, max = 4.65).Those with TB (n = 12) demonstrated a SUVmax of 3.99 ± 2.28, and a median value of 3.71 (pct25 = 2.19, pct75 = 4.95). In patients with other benign lesions (n = 10), the following values were observed: a SUVmax of 2.70 ± 1.31, a median value of 2.50 (pct25 = 1.76, pct75 = 3.59). The mean values of these three types of pathology were not statistically significant (p = 0.1919), and therefore the SUVmax could not be used to accurately distinguish between these lesions using both early and delayed imaging.This study, as the first (68)Ga-citrate PET/CT in humans for the in vivo imaging of lung pathology, demonstrated its potential for the detection of both malignancy and TB. However, (68)Ga-citrate seemed incapable of providing a clear distinction between malignant and benign lung lesions in a setting with a high prevalence of granulomatous diseases such as TB.

Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET), technetium-99m hexamethylpropylene amine oxime (HMPAO)-labelled white blood cell (WBC) scintigraphy and bone scintigraphy were used in the evaluation of total knee arthroplasties (TKAs). We prospectively included 21 patients who had a three-phase bone scan for exclusion of infection of TKAs. Four hours after injection of 185 MBq 99mTc-HMPAO-labelled WBCs, planar and single-photon emission tomographic (SPET) imaging was performed. Planar imaging was repeated at 24 h p.i. Consecutively images of the knees were obtained with a dedicated PET system 60 min following the injection of 370 MBq of FDG. Focal tracer uptake was scored on SPET and PET visually (0=no uptake, 4=intense uptake). In addition, SUV (standardised uptake value) per voxel was calculated from attenuation-corrected PET images using the MLAA algorithm. Focal uptake at the bone-prosthesis interface was used as the criterion for infection before and after correlation with the third phase of the bone scan. Final diagnosis was based on operative findings, culture and clinical outcome. In the infected TKAs, the WBC scan showed focal activity of grade 2 (n=2), 3 (n=l) or 4 (n=2). PET scan revealed focal activity of grade 4 (n=5) or 3 (n=1). WBC scan alone had a specificity for infection of 53% [positive predictive value (PPV) 42%, sensitivity 100%], compared with 73% for PET scan (PPV 60%, sensitivity 100%). Considering only lesions at the bone-prosthesis interface that were also present on the third phase of the bone scan, we found a specificity of 93% (PPV 83%) for WBC scan. Using these criteria, a specificity of 80% (PPV 67%) was obtained for PET scan. Two out of three false-positive PET scans were due to loosening of the TKA. It is concluded that WBC scintigraphy in combination with bone scintigraphy has a high specificity in the detection of infected TKAs. FDG-PET seems to offer no additional benefit.