225Ac-PSMA-617 radioligand therapy of de novo metastatic hormone-sensitive prostate carcinoma (mHSPC): preliminary clinical findings.

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.

18F-FDG-PET/CT imaging of uterine cervical cancer recurrence in women with and without HIV infection.

BACKGROUND: To compare the rate, time and, pattern of recurrence of cervical cancer between patients with and without HIV infection and to determine factors predicting cervical cancer recurrence in patients evaluated by 18F-FDG-PET/CT. METHODS: We reviewed the 18F-FDG-PET/CT images of patients with histologically proven cervical carcinoma who were presenting with suspected recurrence. We extracted epidemiologic data, previous treatment, histologic subtype, HIV status, viral load and CD4 counts from the electronic laboratory database and the referral form for the 18F-FDG-PET/CT study. RESULTS: We studied 303 women including 112 HIV-infected patients. FIGO stage III disease was present in 131 patients. Of 198 patients with recurrence, 74 were HIV-infected while 124 were not (P=0.849). HIV infected patients were younger (41.99±9.30 years) compared to HIV-uninfected (50.19±11.09), P<0.001. Local recurrence was present in 125 patients while 100 patients had a distant recurrence. Recurrence occurred at a single site in 88 patients and two or more sites in 110 patients. No significant difference in the recurrent patterns between HIV-infected and uninfected patients. Median time to recurrence was 10.50 months (range: 6.00-156.00) among HIV-infected versus 12.00 months (IQR:7.00-312.00) among the uninfected, P=0.065. FIGO stage III (P=0.042) and the presence of histological sub-types other than SCC (P=0.005) were significant predictors of recurrence. HIV infection by itself was not significant in predicting recurrence (P=0.843). CONCLUSIONS: HIV infection has no significant impact on the rate, time or pattern of recurrence in women with suspected cervical carcinoma recurrence. Advanced disease and histological variant other than SCC are predictive of recurrence.

Quantification of 18F-fluorodeoxyglucose uptake to detect residual nodal disease in locally advanced head and neck squamous cell carcinoma after chemoradiotherapy: results from the ECLYPS study.

BACKGROUND: The Hopkins criteria were introduced for nodal response evaluation after therapy in head and neck cancer, but its superiority over quantification is not yet confirmed. METHODS: SUVbody weight thresholds and lesion-to-background ratios were explored in a prospective multicenter study of standardized FDG-PET/CT 12 weeks after CRT in newly diagnosed locally advanced head and neck squamous cell carcinoma (LAHNSCC) patients (ECLYPS). Reference standard was histology, negative FDG-PET/CT at 12 months after treatment or ≥ 2 years of negative follow-up. Area under the receiver operator characteristics curves (AUROC) were estimated and obtained thresholds were validated in an independent cohort of HNSCC patients (n = 127). RESULTS: In ECLYPS, 124 patients were available for quantification. With a median follow-up of 20.4 months, 23 (18.5%) nodal neck recurrences were observed. A SUV70 threshold of 2.2 (AUROC = 0.89; sensitivity = 79.7%; specificity = 80.8%) was identified as optimal metric to identify nodal recurrence within 1 year after therapy. For lesion-to-background ratios, an SUV50/SUVliver threshold of 0.96 (AUROC = 0.89; sensitivity = 79.7%; specificity = 82.8%) had the best performance. Compared with Hopkins criteria (AUROC = 0.81), SUV70 and SUV50/SUVliver provided a borderline significant (p = 0.040 and p = 0.094, respectively) improvement. Validation of thresholds yielded similar AUROC values (SUV70 = 0.93, SUV50/SUVliver = 0.95), and were comparable to the Hopkins score (AUROC = 0.91; not statistically significant). CONCLUSION: FDG quantification detects nodal relapse in LAHNSCC patients. When using EARL standardized PET acquisitions and reconstruction, absolute SUV metrics (SUV70 threshold 2.2) prove robust, yet ratios (SUV50/SUVliver, threshold 0.96) may be more useful in routine clinical care. In this setting, the diagnostic value of quantification is comparable to the Hopkins criteria. TRIAL REGISTRATION: US National Library for Medicine, NCT01179360. Registered 11 August 2010, https://clinicaltrials.gov/ct2/show/NCT01179360.

Blood-brain barrier transport kinetics of NOTA-modified proteins: the somatropin case.

BACKGROUND: Chemical modifications such as PEG, polyamine and radiolabeling on proteins can alter their pharmacokinetic behavior and their blood-brain barrier (BBB) transport characteristics. NOTA, i.e. 1,4,7-triazacyclononane-1,4,7-triacetic acid, is a bifunctional chelating agent that has attracted the interest of the scientific community for its high complexation constant with metals like gallium. Until now, the comparative BBB transport characteristics of NOTA-modified proteins versus unmodified proteins are not yet described. METHODS: Somatropin (i.e. recombinant human growth hormone), NOTA-conjugated somatropin and gallium-labelled NOTA-conjugated somatropin were investigated for their brain penetration characteristics (multiple time regression and capillary depletion [CD]) in an in vivo mice model to determine the blood-brain transfer properties. RESULTS: The three compounds showed comparable initial brain influx, with Kin=0.38±0.14 µL/(g×min), 0.36±0.16 µL/(g×min) and 0.28±0.18 µL/(g×min), respectively. CD indicated that more than 80% of the influxed compounds reached the brain parenchyma. All three compounds were in vivo stable in serum and brain during the time frame of the experiments. CONCLUSIONS: Our results show that modification of NOTA as well as gallium chelation onto proteins, in casu somatropin, does not lead to a significantly changed pharmacokinetic profile at the blood-brain barrier.

68Ga-citrate PET/CT in tuberculosis: a pilot study.

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.

PSMA-Targeting Positron Emission Agents for Imaging Solid Tumors Other Than Non-Prostate Carcinoma: A Systematic Review.

Despite its name, prostate-specific membrane antigen (PSMA) has been shown using immunohistochemistry (IHC) to also be over-expressed in the tumor neovasculature of a wide variety of solid tumors other than prostate carcinoma. Accordingly, positron-emitting radiolabeled small molecules targeting PSMA, initially developed for positron emission tomography in prostate carcinomas, are currently being explored for their staging and restaging potential as an alternative imaging modality in other solid tumor types where 18-F-fluorodeoxyglucose (FDG)-PET imaging has low diagnostic accuracy. In this paper, the currently available literature in this field is reviewed. Preliminary, mainly retrospective studies are encouraging, with evidence of improved diagnostic sensitivity and specificity in clear cell renal carcinoma, glioma, and hepatocellular carcinoma, leading to a change in patient management in several patients. However, the results published thus far warrant confirmation by larger prospective studies additionally assessing the longitudinal impact on patient outcomes.

68Ga-PSMA-11 PET/CT in primary staging of prostate carcinoma: preliminary results on differences between black and white South-Africans.

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.

Reversible myocardial perfusion defects in patients not suffering from obstructive epicardial coronary artery disease as assessed by coronary angiography.

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, Behçet'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.

Diagnostic sensitivity of Tc-99m HYNIC PSMA SPECT/CT in prostate carcinoma: A comparative analysis with Ga-68 PSMA PET/CT.

BACKGROUND: Emerging data from published studies are demonstrating the superiority of Ga-68 PSMA PET/CT imaging in prostate cancer. However, the low yield of the Ge-68/Ga-68 from which Gallium-68 is obtained and fewer installed PET/CT systems compared to the SPECT imaging systems may limit its availability. We, therefore, evaluated in a head-to-head comparison, the diagnostic sensitivity of Ga-68 PSMA PET/CT and Tc-99m PSMA SPECT/CT in patients with prostate cancer. METHODS: A total of 14 patients with histologically confirmed prostate cancer were prospectively recruited to undergo Ga-68 PSMA PET/CT and Tc-99m HYNIC PSMA SPECT/CT. The mean age of patients was 67.21 ± 8.15 years and the median PSA level was 45.18 ng/mL (range = 1.51-687 ng/mL). SUVmax of all lesions and the size of lymph nodes with PSMA avidity on Ga-68 PSMA PET/CT were determined. Proportions of these lesions detected on Tc-99m HYNIC PSMA SPECT/CT read independent of PET/CT findings were determined. RESULTS: A total of 46 lesions were seen on Ga-68 PSMA PET/CT localized to the prostate (n = 10), lymph nodes (n = 24), and bones (n = 12). Of these, Tc-99m HYNIC PSMA SPECT/CT detected 36 lesions: Prostate = 10/10 (100%), lymph nodes = 15/24 (62.5%), and bones = 11/12 (91.7%) with an overall sensitivity of 78.3%. Lesions detected on Tc-99m HYNIC PSMA SPECT/CT were bigger in size (P < 0.001) and had higher SUVmax (P < 0.001) as measured on Ga-68 PSMA PET/CT compared to those lesions that were not detected. All lymph nodes greater than 10 mm in size were detected while only 28% of nodes less than 10 mm were detected by Tc-99m HYNIC PSMA SPECT/CT. In a univariate analysis, Lymph node size (P = 0.033) and the SUVmax of all lesions (P = 0.007) were significant predictors of lesion detection on Tc-99m HYNIC PSMA SPECT/CT. CONCLUSION: Tc-99m HYNIC PSMA may be a useful in imaging of prostate cancer although with a lower sensitivity for lesion detection compared to Ga-68 PSMA PET/CT. Its use is recommended when Ga-68 PSMA is not readily available, in planning radio-guided surgery or the patient is being considered for radio-ligand therapy with Lu-177 PSMA. It performs poorly in detecting small-sized lesions hence its use is not recommended in patients with small volume disease.

In Vitro Functional Quality Characterization of NOTA-Modified Somatropins.

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 (pEC50 values between 9.53 and 9.78) and efficacy (Emax values between 130 and 160%). We conclude that the NOTA-modified somatropins do not possess a significantly different in vitro functionality profile compared to unmodified somatropin. Techniques such as SEC, MS, and CD, traditionally used in the physicochemical characterization of proteins have a demonstrated potential use in the functionality evaluation not only in drug discovery and development but also in quality control settings.

Metabolic and morphological measurements of subcutaneous and visceral fat and their relationship with disease stage and overall survival in newly diagnosed pancreatic adenocarcinoma : Metabolic and morphological fat measurements in pancreatic adenocarcinoma.

PURPOSE: 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. METHODS: 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). RESULTS: 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). CONCLUSION: 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.

68Ga-PSMA-HBED-CC PET imaging in breast carcinoma patients.

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.

Stable metabolic disease on FDG-PET provides information on response to endocrine therapy for breast cancer.

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.

Negative 18F-FDG PET and positive CT and MRI findings in multifocal splenic hamartoma.

We report our fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18FFDG PET/CT) findings in a 51 years old female presenting with B symptoms, respectively fever, night sweats and malaise, that underwent an 18F-FDG PET/CT examination to exclude underlying lymphomatous disease. Whereas 18F-FDG PET scan findings were negative, CT put to evidence the presence of multiple small lesions suggestive for multifocal hamartoma. On a subsequently performed magnetic resonance imaging (MRI) of the spleen, multiple infracentimetric foci were visualized displaying characteristic findings for hamartoma. During a follow-up period of two years no change in size or characteristics of these lesions occurred. CONCLUSION: The normal :F-FDG PET/CT findings suggested that, at least in this patient, splenic hamartoma may display a similar :F-FDG avidity when compared to normal splenic tissue. Alternatively, due to the infra-centrimeric size of the hamartoma and spill-over from :F-FDG activity from neighbouring normal tissue, the true 18F-FDG avidity of the hamartomas present might also be overestimated.

Accuracy of bone SPECT/CT for identifying hardware loosening in patients who underwent lumbar fusion with pedicle screws.

BACKGROUND: 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 standard METHODS: A 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. RESULTS: 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. CONCLUSIONS: 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.

Review of clinically accessible methods to determine lean body mass for normalization of standardized uptake values.

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.

Preclinical validation of automated dual-energy X-ray absorptiometry and computed tomography-based body composition measurements.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%). CONCLUSION: The most suited method for automated tissue segmentation is CT and can become a valuable tool in quantitative nuclear medicine.

[18F]FDG PET/CT for the assessment of the volume of the spleen.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Echium oil is not protective against weight loss in head and neck cancer patients undergoing curative radio(chemo)therapy: a randomised-controlled trial.

BACKGROUND: Therapy-induced mucositis and dysphagia puts head and neck (H&N) cancer patients at increased risk for developing cachexia. Omega-3 fatty acids (n-3 FA) have been suggested to protect against cachexia. We aimed to examine if echium oil, a plant source of n-3 FA, could reduce weight loss in H&N cancer patients undergoing radio(chemo)therapy with curative intent. METHODS: In a double-blind trial, patients were randomly assigned to echium oil (intervention (I) group; 7.5 ml bis in die (b.i.d.), 235 mg/ml α-linolenic acid (ALA) + 95 mg/ml stearidonic acid (SDA) + 79 mg/ml γ-linolenic acid (GLA)) or n-3 FA deficient sunflower oil high oleic (control (C) group; 7.5 ml b.i.d.) additional to standard nutritional support during treatment. Differences in percentage weight loss between both groups were analysed according to the intention-to-treat principle. Erythrocyte FA profile, body composition, nutritional status and quality of life were collected. RESULTS: Ninety-one eligible patients were randomised, of whom 83 were evaluable. Dietary supplement adherence was comparable in both groups (median, I: 87%, C: 81%). At week 4, the I group showed significantly increased values of erythrocyte n-3 eicosapentanoic acid (EPA, 14% vs -5%) and n-6 GLA (42% vs -20%) compared to the C group, without a significant change in n-6 arachidonic acid (AA, 2% vs -1%). Intention-to-treat analysis could not reveal a significant reduction in weight loss related to echium oil consumption (median weight loss, I: 8.9%, C: 7.6%). Also, no significant improvement was observed in the other evaluated anthropometric parameters. CONCLUSIONS: Echium oil effectively increased erythrocyte EPA and GLA FAs in H&N cancer patients. It failed however to protect against weight loss, or improve nutritional parameters. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01596933.