Detection rate of PET/CT in patients with biochemical relapse of prostate cancer using [<Superscript>68</Superscript>Ga]PSMA I&amp;T and comparison with published data of [<Superscript>68</Superscript>Ga]PSMA HBED-CC

Purpose

To determine the detection rate of PET/CT in biochemical relapse of prostate cancer using [⁶⁸Ga]PSMA I&T and to compare it with published detection rates of [⁶⁸Ga]PSMA HBED-CC.

Methods

We performed a retrospective analysis in 83 consecutive patients with documented biochemical relapse after prostatectomy. All patients underwent whole body [⁶⁸Ga]PSMA I&T PET/CT. PET/CT images were evaluated for presence of local recurrence, lymph node metastases, and distant metastases. Proportions of positive PET/CT results were calculated for six subgroups with increasing prostate specific antigen (PSA) levels (<0.5 ng/mL, 0.5 to <1.0 ng/mL, 1.0 to <2.0 ng/mL, 2.0 to <5.0 ng/mL, 5.0 to <10.0, ≥10.0 ng/mL). Detection rates of [⁶⁸Ga]PSMA I&T were statistically compared with published detection rates of [⁶⁸Ga]PSMA HBED-CC using exact Fisher’s test.

Results

Median PSA was 0.81 (range: 0.01 – 128) ng/mL. In 58/83 patients (70 %) at least one [⁶⁸Ga]PSMA I&T positive lesion was detected. Local recurrent cancer was present in 18 patients (22 %), lymph node metastases in 29 patients (35 %), and distant metastases in 15 patients (18 %). The tumor detection rate was positively correlated with PSA levels, resulting in detection rates of 52 % (<0.5 ng/mL), 55 % (0.5 to <1.0 ng/mL), 70 % (1.0 to <2.0 ng/mL), 93 % (2.0 to <5.0 ng/mL), 100 % (5.0 to <10.0 ng/mL), and 100 % (≥10.0 ng/mL). There was no significant difference between the detection rate of [⁶⁸Ga]PSMA I&T and published detection rates of [⁶⁸Ga]PSMA HBED-CC (all

Conclusions

[⁶⁸Ga]PSMA I&T PET/CT has high detection rates of recurrent prostate cancer that are comparable to [⁶⁸Ga]PSMA HBED-CC.

     

The impact of [<Superscript>68</Superscript>Ga]PSMA I&amp;T PET/CT on radiotherapy planning in patients with prostate cancer

Purpose

To determine the impact of Gallium-68-labled prostate-specific membrane antigen positron-emission tomography/computed tomography ([⁶⁸Ga]PSMA PET/CT) on radiotherapy planning for primary disease, biochemical cancer relapse, and advanced disease of prostate cancer.

Methods

A total of 106 patients with prostate cancer scheduled for radiation therapy underwent 120 [⁶⁸Ga]PSMA PET/CT scans prior to radiotherapy treatment. In 20 cases, patients underwent [⁶⁸Ga]PSMA PET/CT for primary therapy (PT), 75 cases were referred for biochemical relapse after surgery (RL), and 25 cases were intended for palliative treatment of localized metastases (MD). We retrospectively compared the impact of [⁶⁸Ga]PSMA PET/CT on lesion detection and treatment decision to CT alone.

Results

[⁶⁸Ga]PSMA PET/CT revealed a total of 271 positive lesions, whereas CT detected 86 lesions (32%). Overall, the radiotherapy regime was changed in 55 of 120 cases (46%) based on the higher detection rate of [⁶⁸Ga]PSMA PET/CT: in 15% of cases with PT, in 43% of cases with RL, and in 44% of cases with MD.

Conclusion

[⁶⁸Ga]PSMA PET/CT is superior to CT alone for lesion detection in prostate cancer, thereby significantly impacting on radiotherapy planning for primary disease, biochemical cancer relapse, and advanced disease of prostate cancer.

     

The diagnostic value of [<Superscript>18</Superscript>F]FDG PET for the detection of chronic osteomyelitis and implant-associated infection

Purpose

The diagnosis of osteomyelitis and implant-associated infections in patients with nonspecific laboratory or radiological findings is often unsatisfactory. We retrospectively evaluated the contributions of [¹⁸F]FDG PET and [¹⁸F]FDG PET/CT to the diagnosis of osteomyelitis and implant-associated infections, enabling timely and appropriate decision-making for further therapy options.

Methods

[¹⁸F]FDG PET or PET/CT was performed in 215 patients with suspected osteomyelitis or implant-associated infections between 2000 and 2013. We assessed the diagnostic accuracy of both modalities together and separately with reference to intraoperative microbial findings, with a mean clinical follow-up of 69?±?49 months.

Results

Infections were diagnosed clinically in 101 of the 215 patients. PET and PET/CT scans revealed 87 true-positive, 76 true-negative, 38 false-positive, and 14 false-negative results, indicating a sensitivity of 86 %, a specificity of 67 %, a positive predictive value (PPV) of 70 %, a negative predictive value (NPV) of 84 % and an accuracy of 76 %. The sensitivity of PET/CT was 88 %, but specificity, PPV, NPV and accuracy (76 %, 76 %, 89 % and 82 %, respectively) were higher than those of stand-alone PET.

Conclusion

[¹⁸F]FDG PET is able to identify with high sensitivity the presence of osteomyelitis in orthopaedic surgery patients with nonspecific clinical symptoms of infection.

     

Repeatability of tumour hypoxia imaging using [<Superscript>18</Superscript>F]EF5 PET/CT in head and neck cancer

Purpose

Hypoxia contributes to radiotherapy resistance and more aggressive behaviour of several types of cancer. This study was designed to evaluate the repeatability of intratumour uptake of the hypoxia tracer [¹⁸F]EF5 in paired PET/CT scans.

Methods

Ten patients with newly diagnosed head and neck cancer (HNC) received three static PET/CT scans before chemoradiotherapy: two with [¹⁸F]EF5 a median of 7 days apart and one with [¹⁸F]FDG. Metabolically active primary tumour volumes were defined in [¹⁸F]FDG images and transferred to co-registered [¹⁸F]EF5 images for repeatability analysis. A tumour-to-muscle uptake ratio (TMR) of 1.5 at 3 h from injection of [¹⁸F]EF5 was used as a threshold representing hypoxic tissue.

Results

In 10 paired [¹⁸F]EF5 PET/CT image sets, SUVmean, SUVmax, and TMR showed a good correlation with the intraclass correlation coefficients of 0.81, 0.85, and 0.87, respectively. The relative coefficients of repeatability for these parameters were 15%, 17%, and 10%, respectively. Fractional hypoxic volumes of the tumours in the repeated scans had a high correlation using the Spearman rank correlation test (r = 0.94). In a voxel-by-voxel TMR analysis between the repeated scans, the mean of Pearson correlation coefficients of individual patients was 0.65. The mean (± SD) difference of TMR in the pooled data set was 0.03 ± 0.20.

Conclusion

Pretreatment [¹⁸F]EF5 PET/CT within one week shows high repeatability and is feasible for the guiding of hypoxia-targeted treatment interventions in HNC.

     

[<Superscript>18</Superscript>F]FDG PET accurately differentiates infected and non-infected non-unions after fracture fixation

Purpose

Complete fracture healing is crucial for good patient outcomes. A major complication in the treatment of fractures is non-union. The pathogenesis of non-unions is not always clear, although implant-associated infections play a significant role, especially after surgical treatment of open fractures. We aimed to evaluate the value of [¹⁸F]FDG PET in suspected infections of non-union fractures.

Methods

We retrospectively evaluated 35 consecutive patients seen between 2000 and 2015 with suspected infection of non-union fractures, treated at a level I trauma center. The patients underwent either [¹⁸F]FDG PET/CT (N?=?24), [¹⁸F]FDG PET (N?=?11) plus additional CT (N?=?8), or conventional X-ray (N?=?3). Imaging findings were correlated with final diagnosis based on intraoperative culture or follow-up.

Results

In 13 of 35 patients (37 %), infection was proven by either positive intraoperative tissue culture (N?=?12) or positive follow-up (N?=?1). [¹⁸F]FDG PET revealed 11 true-positive, 19 true-negative, three false-positive, and two false-negative results, indicating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 85 %, 86 %, 79 %, 90 %, and 86 %, respectively. The SUV_max was 6.4?±?2.7 in the clinically infected group and 3.0?±?1.7 in the clinically non-infected group (p <0.01). The SUV_ratio was 5.3?±?3.3 in the clinically infected group and 2.6?±?1.5 in the clinically non-infected group (p <0.01).

Conclusion

[¹⁸F]FDG PET differentiates infected from non-infected non-unions with high accuracy in patients with suspected infections of non-union fractures, for whom other clinical findings were inconclusive for a local infection. [¹⁸F]FDG PET should be considered for therapeutic management of non-unions.

     

The value of [<Superscript>11</Superscript>C]-acetate PET and [<Superscript>18</Superscript>F]-FDG PET in hepatocellular carcinoma before and after treatment with transarterial chemoembolization and bevacizumab

Purpose

This prospective study was to investigate the value of [¹¹C]-acetate PET and [¹⁸F]-FDG PET in the evaluation of hepatocellular carcinoma (HCC) before and after treatment with transarterial chemoembolization (TACE) and vascular endothelial growth factor (VEGF) antibody (bevacizumab).

Methods

Twenty-two patients (three women, 19 men; 62 ± 8 years) with HCC verified by histopathology were treated with TACE and bevacizumab (n = 11) or placebo (n = 11). [¹¹C]-acetate PET and [¹⁸F]-FDG PET were performed before and after TACE with bevacizumab or placebo. Comparisons between groups were performed with t-tests and Chi-squared tests, where appropriate. Overall survival (OS) was defined as the time from start of bevacizumab or placebo until the date of death/last follow-up, respectively.

Results

The patient-related sensitivity of [¹¹C]-acetate PET, [¹⁸F]-FDG PET, and combined [¹¹C]-acetate and [¹⁸F]-FDG PET was 68%, 45%, and 73%, respectively. There was a significantly higher rate of conversion from [¹¹C]-acetate positive lesions to negative lesions in patients treated with TACE and bevacizumab as compared with that in patients with TACE and placebo (p < 0.05). In patients with negative acetate PET, the mean OS in patients treated with TACE and bevacizumab was 259 ± 118 days and was markedly shorter as compared with that (668 ± 217 days) in patients treated with TACE and placebo (p < 0.05). In patients treated with TACE and placebo, there was significant difference in mean OS in patients with positive FDG PET as compared with that in patients with negative FDG PET (p < 0.05). The HCC lesions had different tracer avidities showing the heterogeneity of HCC.

Conclusions

Our study suggests that combining [¹⁸F]-FDG with [¹¹C]-acetate PET could be useful for the management of HCC patients and might also provide relevant prognostic and molecular heterogeneity information.

     

Phase IIa clinical study of [<Superscript>18</Superscript>F]fluciclovine: efficacy and safety of a new PET tracer for brain tumors

Objective

[¹⁸F]Fluciclovine (anti-[¹⁸F]FACBC) has demonstrated diagnostic efficacy for cancers of the brain where [¹⁸F]fludeoxyglucose has limitations. We conducted a phase IIa study of anti-[¹⁸F]FACBC to assess its accumulation pattern and safety in patients with malignant glioma.

Methods

Five patients with glioma scheduled for brain tumor resection received anti-[¹⁸F]FACBC. Brain positron emission tomography (PET) was performed following intravenous administration of anti-[¹⁸F]FACBC, and subsequently, preoperative gadolinium contrast-enhanced T1-weighted (CE-T1W) magnetic resonance imaging (MRI) was performed for surgery. Specimens for histopathological evaluation were collected during surgery, and their location was precisely determined on CE-T1W MRI and anti-[¹⁸F]FACBC PET/CT images. In addition, tumor extent defined on the MRI and PET/CT images was compared. To determine time–activity curves for anti-[¹⁸F]FACBC uptake in brain tumor and normal tissues, regions of interest were set in the brain tumor, contralateral normal tissue and the cerebellum, and their standardized uptake values (SUV) were calculated. The safety of anti-[¹⁸F]FACBC was assessed based on subjective symptoms and objective findings, electrocardiograms, vital signs, laboratory results, and the incidence of adverse events.

Results

Anti-[¹⁸F]FACBC accumulated in the malignant gliomas of all patients. CE-T1W MRI detected gliomas in all patients, but anti-[¹⁸F]FACBC PET/CT generally delineated wider regions of tumor extent than CE-T1W MRI. Two of the histopathologically confirmed tumors were located in regions that were defined using anti-[¹⁸F]FACBC PET/CT, but not using CE-T1W MRI. Two patients experienced three mild adverse events: one complained of a dull headache and later a mild headache, and the other showed general malaise. These symptoms resolved spontaneously without treatment. Only the mild headache could not be ruled out from having a causal relationship with anti-[¹⁸F]FACBC. Favorable T/N ratios regarding anti-[¹⁸F]FACBC uptake between tumors and normal control tissues were demonstrated in this trial.

Conclusions

It is suggested that anti-[¹⁸F]FACBC PET/CT has the ability to delineate glioma spread that is undetectable using CE-T1W MRI. Anti-[¹⁸F]FACBC is safe in patients with malignant glioma.This study was registered in the Japan Pharmaceutical Information Center Clinical Trials Information, which is one of the World Health Organization registries (registration number: JapicCTI-111387).

     

Comparison of [<Superscript>68</Superscript>Ga]Ga-PSMA-11 PET/CT with [<Superscript>18</Superscript>F]NaF PET/CT in the evaluation of bone metastases in metastatic prostate cancer patients prior to radionuclide therapy

Aim

The purpose of this study was to investigate the diagnostic performance of ⁶⁸Ga-PSMA-11 PET/CT in the evaluation of bone metastases in metastatic prostate cancer (PC) patients scheduled for radionuclide therapy in comparison to [¹⁸F]sodium fluoride (¹⁸F-NaF) PET/CT.

Methods

Sixteen metastatic PC patients with known skeletal metastases, who underwent both ⁶⁸Ga-PSMA-11 PET/CT and ¹⁸F-NaF PET/CT for assessment of metastatic burden prior to radionuclide therapy, were analysed retrospectively. The performance of both tracers was calculated on a lesion-based comparison. Intensity of tracer accumulation of pathologic bone lesions on ¹⁸F-NaF PET and ⁶⁸Ga-PSMA-11 PET was measured with maximum standardized uptake values (SUV_max) and compared to background activity of normal bone. In addition, SUV_max values of PET-positive bone lesions were analysed with respect to morphologic characteristics on CT. Bone metastases were either confirmed by CT or follow-up PET scan.

Results

In contrast to 468 PET-positive lesions suggestive of bone metastases on ¹⁸F-NaF PET, only 351 of the lesions were also judged positive on ⁶⁸Ga-PSMA-11 PET (75.0%). Intensity of tracer accumulation of pathologic skeletal lesions was significantly higher on ¹⁸F-NaF PET compared to ⁶⁸Ga-PSMA-11 PET, showing a median SUV_max of 27.0 and 6.0, respectively (p?<?0.001). Background activity of normal bone was lower on ⁶⁸Ga-PSMA-11 PET, with a median SUV_max of 1.0 in comparison to 2.7 on ¹⁸F-NaF PET; however, tumour to background ratio was significantly higher on ¹⁸F-NaF PET (9.8 versus 5.9 on ⁶⁸Ga-PSMA-11 PET; p?=?0.042). Based on morphologic lesion characterisation on CT, ¹⁸F-NaF PET revealed median SUV_max values of 23.6 for osteosclerotic, 35.0 for osteolytic, and 19.0 for lesions not visible on CT, whereas on ⁶⁸Ga-PSMA-11 PET median SUV_max values of 5.0 in osteosclerotic, 29.5 in osteolytic, and 7.5 in lesions not seen on CT were measured. Intensity of tracer accumulation between¹⁸F-NaF PET and ⁶⁸Ga-PSMA-11 PET was significantly higher in osteosclerotic (p?<?0.001) and lesions not visible on CT (p?=?0.012).

Conclusion

In comparison to ⁶⁸Ga-PSMA-11 PET/CT, ¹⁸F-NaF PET/CT detects a higher number of pathologic bone lesions in advanced stage PC patients scheduled for radionuclide therapy. Our data suggest that ⁶⁸Ga-PSMA-11 PET should be combined with ¹⁸F-NaF PET in PC patients with skeletal metastases for restaging prior to initiation or modification of therapy.

     

Multimodal correlation of dynamic [<Superscript>18</Superscript>F]-AV-1451 perfusion PET and neuronal hypometabolism in [<Superscript>18</Superscript>F]-FDG PET

Purpose

Cerebral glucose metabolism measured with [18F]-FDG PET is a well established marker of neuronal dysfunction in neurodegeneration. The tau-protein tracer [18F]-AV-1451 PET is currently under evaluation and shows promising results. Here, we assess the feasibility of early perfusion imaging with AV-1451 as a substite for FDG PET in assessing neuronal injury.

Methods

Twenty patients with suspected neurodegeneration underwent FDG and early phase AV-1451 PET imaging. Ten one-minute timeframes were acquired after application of 200 MBq AV-1451. FDG images were acquired on a different date according to clinical protocol. Early AV-1451 timeframes were coregistered to individual FDG-scans and spatially normalized. Voxel-wise intermodal correlations were calculated on within-subject level for every possible time window. The window with highest pooled correlation was considered optimal. Z-transformed deviation maps (ZMs) were created from both FDG and early AV-1451 images, comparing against FDG images of healthy controls.

Results

Regional patterns and extent of perfusion deficits were highly comparable to metabolic deficits. Best results were observed in a time window from 60 to 360 s (r = 0.86). Correlation strength ranged from r = 0.96 (subcortical gray matter) to 0.83 (frontal lobe) in regional analysis. ZMs of early AV-1451 and FDG images were highly similar.

Conclusion

Perfusion imaging with AV-1451 is a valid biomarker for assessment of neuronal dysfunction in neurodegenerative diseases. Radiation exposure and complexity of the diagnostic workup could be reduced significantly by routine acquisition of early AV-1451 images, sparing additional FDG PET.

     

Preclinical and first clinical experience with the gastrin-releasing peptide receptor-antagonist [<Superscript>68</Superscript>Ga]SB3 and PET/CT

Purpose

Gastrin-releasing peptide receptors (GRPR) represent attractive targets for tumor diagnosis and therapy because of their overexpression in major human cancers. Internalizing GRPR agonists were initially proposed for prolonged lesion retention, but a shift of paradigm to GRPR antagonists has recently been made. Surprisingly, radioantagonists, such as [^99mTc]DB1 (^99mTc-N₄′-DPhe⁶,Leu-NHEt¹³]BBN(6–13)), displayed better pharmacokinetics than radioagonists, in addition to their higher inherent biosafety. We introduce here [⁶⁸Ga]SB3, a [^99mTc]DB1 mimic-carrying, instead of the ^99mTc-binding tetraamine, the chelator DOTA for labeling with the PET radiometal ⁶⁸Ga.

Methods

Competition binding assays of SB3 and [^natGa]SB3 were conducted against [¹²⁵I-Tyr⁴]BBN in PC-3 cell membranes. Blood samples collected 5 min postinjection (pi) of the [⁶⁷Ga]SB3 surrogate in mice were analyzed using high-performance liquid chromatography (HPLC) for degradation products. Likewise, biodistribution was performed after injection of [⁶⁷Ga]SB3 (37 kBq, 100 μL, 10 pmol peptide) in severe combined immunodeficiency (SCID) mice bearing PC-3 xenografts. Eventually, [⁶⁸Ga]SB3 (283?±?91 MBq, 23?±?7 nmol) was injected into 17 patients with breast (8) and prostate (9) cancer. All patients had disseminated disease and had received previous therapies. PET/CT fusion images were acquired 60–115 min pi.

Results

SB3 and [^natGa]SB3 bound to the human GRPR with high affinity (IC₅₀: 4.6?±?0.5 nM and 1.5?±?0.3 nM, respectively). [⁶⁷Ga]SB3 displayed good in vivo stability (>85 % intact at 5 min pi). [⁶⁷Ga]SB3 showed high, GRPR-specific and prolonged retention in PC-3 xenografts (33.1?±?3.9%ID/g at 1 h pi – 27.0?±?0.9%ID/g at 24 h pi), but much faster clearance from the GRPR-rich pancreas (≈160%ID/g at 1 h pi to <17%ID/g at 24 h pi) in mice. In patients, [⁶⁸Ga]SB3 elicited no adverse effects and clearly visualized cancer lesions. Thus, 4 out of 8 (50 %) breast cancer and 5 out of 9 (55 %) prostate cancer patients showed pathological uptake on PET/CT with [⁶⁸Ga]SB3.

Conclusion

[⁶⁷Ga]SB3 showed excellent pharmacokinetics in PC-3 tumor-bearing mice, while [⁶⁸Ga]SB3 PET/CT visualized lesions in about 50 % of patients with advanced and metastasized prostate and breast cancer. We expect imaging with [⁶⁸Ga]SB3 to be superior in patients with primary breast or prostate cancer.

     

Prediction of neoadjuvant radiation chemotherapy response and survival using pretreatment [<Superscript>18</Superscript>F]FDG PET/CT scans in locally advanced rectal cancer

Purpose

The aim of this study was to investigate metabolic and textural parameters from pretreatment [¹⁸F]FDG PET/CT scans for the prediction of neoadjuvant radiation chemotherapy response and 3-year disease-free survival (DFS) in patients with locally advanced rectal cancer (LARC).

Methods

We performed a retrospective review of 74 patients diagnosed with LARC who were initially examined with [¹⁸F]FDG PET/CT, and who underwent neoadjuvant radiation chemotherapy followed by complete resection. The standardized uptake value (mean, peak, and maximum), metabolic volume (MV), and total lesion glycolysis of rectal cancer lesions were calculated using the isocontour method with various thresholds. Using three-dimensional textural analysis, about 50 textural features were calculated for PET images. Response to neoadjuvant radiation chemotherapy, as assessed by histological tumour regression grading (TRG) after surgery and 3-year DFS, was evaluated using univariate/multivariate binary logistic regression and univariate/multivariate Cox regression analyses.

Results

MVs calculated using the thresholds mean standardized uptake value of the liver + two standard deviations (SDs), and mean standard uptake of the liver + three SDs were significantly associated with TRG. Textural parameters from histogram-based and co-occurrence analysis were significantly associated with TRG. However, multivariate analysis revealed that none of these parameters had any significance. On the other hand, MV calculated using various thresholds was significantly associated with 3-year DFS, and MV calculated using a higher threshold tended to be more strongly associated with 3-year DFS. In addition, textural parameters including kurtosis of the absolute gradient (GrKurtosis) were significantly associated with 3-year DFS. Multivariate analysis revealed that GrKurtosis could be a prognostic factor for 3-year DFS.

Conclusion

Metabolic and textural parameters from initial [¹⁸F]FDG PET/CT scans could be indexes to assess tumour heterogeneity for the prediction of neoadjuvant radiation chemotherapy response and recurrence in LARC.

     

Imaging children suffering from lymphoma: an evaluation of different <Superscript>18</Superscript>F-FDG PET/MRI protocols compared to whole-body DW-MRI

Objectives

The objectives of this study were to evaluate and compare the diagnostic potential of different PET/MRI reading protocols, entailing non-enhanced / contrast-enhanced and diffusion-weighted ¹⁸F–FDG PET/MR imaging and whole-body diffusion-weighted MRI for lesion detection and determination of the tumor stage in pediatric lymphoma patients.

Methods

A total of 28 ¹⁸F–FDG PET/MRI datasets were included for analysis of four different reading protocols: (1) PET/MRI utilizing sole unenhanced T2w and T1w imaging, (2) PET/MRI utilizing additional contrast enhanced sequences, (3) PET/MR imaging utilizing unenhanced, contrast enhanced and DW imaging or (4) WB-DW-MRI. Statistical analyses were performed on a per-patient and a per-lesion basis. Follow-up and prior examinations as well as histopathology served as reference standards.

Results

PET/MRI correctly identified all 17 examinations with active lymphoma disease, while WB-DW-MRI correctly identified 15/17 examinations. Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were 96%, 96.5%, 97%, 95%, and 96% for PET/MRI₁; 97%, 96.5%, 97%, 96.5%, and 97% for PET/MRI₂; 97%, 96.5%, 97%, 96.5%, and 97% for PET/MRI₃ and 77%, 96%, 96%, 78.5% and 86% for MRI-DWI.

Conclusion

¹⁸F–FDG PET/MRI is superior to WB-DW-MRI in staging pediatric lymphoma patients. Neither application of contrast media nor DWI leads to a noticeable improvement of the diagnostic accuracy of PET/MRI. Thus, unenhanced PET/MRI may play a crucial role for the diagnostic work-up of pediatric lymphoma patients in the future.

     

Comparison of standard and delayed imaging to improve the detection rate of [<Superscript>68</Superscript>Ga]PSMA I&amp;T PET/CT in patients with biochemical recurrence or prostate-specific antigen persistence after primary therapy for prostate cancer

Purpose

The aim of this study was to assess the value of dual-time point imaging in PET/CT for detection of biochemically recurrent or persistent prostate cancer, using the prostate-specific membrane antigen (PSMA) ligand [⁶⁸Ga]PSMA I&T.

Methods

240 patients who underwent a [⁶⁸Ga]PSMA I&T PET/CT in the context of biochemical relapse of prostate cancer were included in this retrospective analysis. Imaging consisted of a standard whole-body PET/CT (1 h p.i.), followed by delayed (3 h p.i.) imaging of the abdomen. PSA-stratified proportions of positive PET/CT results, standardized uptake values and target-to-background ratios were analyzed, and compared between standard and delayed imaging.

Results

The overall detection rates of [⁶⁸Ga]PSMA I&T PET/CT were 94.2, 71.8, 58.6, 55.9 and 38.9% for PSA levels of ≥2, 1 to <2, 0.5 to <1, >0.2 to <0.5, and 0.01 to 0.2 ng/mL, respectively. Although the target-to-background ratio improved significantly over time (P?<?0.0001), the majority (96.6%) of all lesions suggestive of recurrent disease could already be detected in standard imaging. Delayed imaging at 3 h p.i. exclusively identified pathologic findings in 5.4% (10/184) of abnormal [⁶⁸Ga]PSMA I&T PET/CT scans, and exclusively detected 3.4% (38/1134) of all lesions suggestive of recurrent disease.

Conclusions

[⁶⁸Ga]PSMA I&T PET/CT shows high detection rates in patients with prostate-specific antigen persistence or biochemical recurrence of prostate cancer. Delayed imaging can detect lesions with improved contrast compared to standard imaging. However, the impact on detection rates was limited in this study.

     

Evaluation of <Superscript>68</Superscript>Ga-DOTATOC PET/MRI for whole-body staging of neuroendocrine tumours in comparison with <Superscript>68</Superscript>Ga-DOTATOC PET/CT

Objectives

To compare the diagnostic performance of ⁶⁸Ga-DOTATOC PET/MRI and ⁶⁸Ga-DOTATOC PET/CT in the whole-body staging of patients with neuroendocrine tumours (NET).

Methods

Thirty patients with histopathologically confirmed NET underwent PET/CT and PET/MRI in a single-injection protocol. PET/CT and PET/MRI scans were prospectively evaluated with regard to lesion count, localization, nature (NET/non-NET), and conspicuity (four-point scale). Histopathology and follow-up imaging served as the reference standards. The proportions of NET and non-NET lesions rated correctly were compared using McNemar’s chi-squared test. The Wilcoxon test was used to assess differences in SUVmax and lesion conspicuity. The correlation between the SUVmax for the same lesions from each modality was analysed using Pearson’s correlation coefficient (r).

Results

According to the reference standard, there were 197 lesions (142 NET, 55 non-NET). Lesion-based analysis showed a higher proportion of correctly rated NET lesions on PET/MRI than on PET/CT (90.8% vs. 86.7%, p?=?0.031), whereas on PET/CT there was a higher proportion of correctly rated non-NET lesions (94.5% vs. 83.6%, p?=?0.031). SUVmax was strongly correlated (r?=?0.86; p?<?0.001) and did not differ significantly (p?=?0.35) between the modalities. Overall conspicuity and NET lesion conspicuity were higher on PET/MRI (both p?<?0.01).

Conclusions

Ga-DOTATOC PET/MRI yielded a higher proportion of correctly rated NET lesions and should be regarded as a valuable alternative to ⁶⁸Ga-DOTATOC PET/CT in whole-body staging of NET patients.

Key Points

? ⁶⁸ Ga-DOTATOC PET/MRI correctly identified more NET lesions than ⁶⁸ Ga-DOTATOC PET/CT. ? ⁶⁸ Ga-DOTATOC PET/MRI provides better NET lesion conspicuity than ⁶⁸ Ga-DOTATOC PET/CT. ? SUVmax values from the two modalities are strongly correlated and do not differ significantly.

     

Diagnostic Value of <Superscript>18</Superscript>F-FDG PET/CT and MRI in the Preoperative Evaluation of Uterine Carcinosarcoma

Purpose

This study aimed to compare the diagnostic value of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and magnetic resonance imaging (MRI) in the preoperative evaluation of uterine carcinosarcoma.

Methods

Fifty-four women with pathologically confirmed uterine carcinosarcoma who underwent preoperative FDG PET/CT and MRI from June 2006 to November 2016 were included. Pathologic findings from primary tumor lesions, para-aortic and pelvic lymph node (LN) areas, and peritoneal seeding lesions were compared with the FDG PET/CT and MRI findings. The maximum standardized uptake value (SUVmax) of the primary tumor and LN was obtained. The tumor-to-liver ratio (TLR) was calculated by dividing the SUVmax of the primary tumor or LN by the mean SUV of the liver.

Results

For detecting primary tumor lesions (n?=?54), the sensitivity and accuracy of FDG PET/CT (53/54) and MRI (53/54) were 98.2%. The sensitivity, specificity, and accuracy of FDG PET/CT versus MRI were as follows: 63.2% (12/19) versus 26.3% (5/19), 100% (35/35) versus 100% (35/35), and 87.0% versus 74.0%, respectively, for pelvic LN areas (p?=?0.016); 85.7% (12/14) versus 42.9% (6/14), 90% (36/40) versus 97.5% (39/40), and 88.9% versus 83.3%, respectively, for para-aortic LN areas (p?=?0.004); and 59.4% (19/32) versus 50% (16/32), 100% (22/22) versus 100% (22/22), and 75.9% versus 70.4%, respectively, for peritoneal seeding lesions (p?=?0.250). For distant metastasis, the sensitivity, specificity, and accuracy of FDG PET/CT were 100 (8/8), 97.8 (45/46), and 98.2%, respectively.

Conclusions

FDG PET/CT showed superior diagnostic accuracy compared to MRI in detecting pelvic and para-aortic LN metastasis in patients with uterine carcinosarcoma. Moreover, FDG PET/CT facilitated the identification of distant metastasis.

     

Diagnostic performance and impact on patient management of <Superscript>68</Superscript>Ga-DOTA-TOC PET/CT for detecting osteomalacia-associated tumours

Purpose

Oncogenic osteomalacia is an endocrine disorder induced by small benign tumours (TIO) producing excessive fibroblast growth factor-23 (FGF23). The only way of curing oncogenic osteomalacia is surgical resection of the culprit TIO, which is extremely difficult to detect using conventional imaging modalities due to its small size and variable location in the body. Since TIO frequently overexpress somatostatin receptors, a clinical utility of SPECT or PET with radiolabelled somatostatin analogues has been reported. Among them, ⁶⁸Ga-DOTA-TOC has recently been granted a marketing authorization, facilitating its routine application. We report here the results of the first series evaluating the diagnostic performance of ⁶⁸Ga-DOTA-TOC PET/CT in detecting TIO and its impact on patient management.

Methods

⁶⁸Ga-DOTA-TOC PET/CT and clinical and imaging data from 15 patients with clinical and biochemical signs of oncogenic osteomalacia were retrospectively reviewed. The ⁶⁸Ga-DOTA-TOC PET/CT findings were compared with the results of post-surgical pathology and clinical and biochemical follow-up.

Results

⁶⁸Ga-DOTA-TOC PET/CT resulted in the detection of one focus suspicious for TIO in nine of 15 patients (60%), and a tumour was surgically removed in eight. Post-operative pathology confirmed a TIO in those eight patients whose symptoms diminished promptly and biochemical anomalies resolved. ⁶⁸Ga-DOTA-TOC PET/CT sensitivity, specificity and accuracy were 73%, 67% and 71%, respectively. ⁶⁸Ga-DOTA-TOC PET/CT findings affected patient management in 67% of cases. In particular, ⁶⁸Ga-DOTA-TOC PET/CT was able to detect the TIO with a negative or a false-positive result of a previous ¹¹¹In-pentetreotide SPECT/CT in 5/8 patients (63%) or a previous FDG PET/CT in 7/11 patients (64%). No close relationship was found between the positivity of ⁶⁸Ga-DOTA-TOC PET/CT and the serum level of a biochemical marker. However, a true-positive result of ⁶⁸Ga-DOTA-TOC PET/CT was obtained in only one patient with a non-elevated serum level of FGF23.

Conclusion

⁶⁸Ga-DOTA-TOC PET/CT is an accurate imaging modality in the detection of TIO; in particular, it is worthwhile after failure of somatostatin receptor SPECT(/CT) or FDG PET/CT.

     

Ability of <Superscript>18</Superscript>F-DOPA PET/CT and fused <Superscript>18</Superscript>F-DOPA PET/MRI to assess striatal involvement in paediatric glioma

Purpose

To assess the diagnostic performance of ¹⁸F-DOPA PET/CT and fused ¹⁸F-DOPA PET/MRI in detecting striatal involvement in children with gliomas.

Methods

This retrospective study included 28 paediatric patients referred to our institution for the presence of primary, residual or recurrent glioma (12 boys, 16 girls; mean age 10.7 years) and investigated with ¹⁸F-DOPA PET/CT and brain MRI. Fused ¹⁸F-DOPA PET/MR images were obtained and compared with PET/CT and MRI images. Accuracy, sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) for striatal involvement were calculated for each diagnostic tool. Univariate and multivariate logistic analyses were applied to evaluate the associations between ¹⁸F-DOPA PET/CT and fused ¹⁸F-DOPA PET/MRI diagnostic results and tumour uptake outside the striatum, grade, dimension and site of striatal involvement (ventral and/or dorsal).

Results

Accuracy, sensitivity, specificity, PPV, and NPV were 100 % for MRI, 93 %, 89 %, 100 %, 100 % and 82 % for ¹⁸F-DOPA PET/MRI, and 75 %, 74 %, 78 %, 88 % and 58 % for ¹⁸F-DOPA PET/CT, respectively. ¹⁸F-DOPA PET/MRI showed a trend towards higher accuracy compared with ¹⁸F-DOPA PET/CT (p?=?0.06). MRI showed significantly higher accuracy compared with ¹⁸F-DOPA PET/CT (p?=?0.01), but there was no significant difference between MRI and ¹⁸F-DOPA PET/MRI. Both univariate and multivariate logistic analyses showed a significant association (OR 8.0 and 7.7, respectively) between the tumour-to-normal striatal uptake (T/S) ratio and the diagnostic ability of ¹⁸F-DOPA PET/CT (p?=?0.03). A strong significant association was also found between involvement of the dorsal striatum and the ¹⁸F-DOPA PET/CT results (p?=?0.001), with a perfect prediction of involvement of the dorsal striatum by ¹⁸F-DOPA PET/MRI.

Conclusion

Physiological striatal ¹⁸F-DOPA uptake does not appear to be a main limitation in the evaluation of basal ganglia involvement.¹⁸F-DOPA PET/CT correctly detected involvement of the dorsal striatum in lesions with a T/S ratio >1, but appeared to be less suitable for evaluation of the ventral striatum. The use of fused ¹⁸F-DOPA PET/MRI further improves the accuracy and is essential for evaluation of the ventral striatum.

     

Preliminary feasibility study on differential diagnosis between radiation-induced cerebral necrosis and recurrent brain tumor by means of [<Superscript>18</Superscript>F]fluoro-borono-phenylalanine PET/CT

Objectives

A previous study reported that a differential diagnosis between glioblastoma progression and radiation necrosis by 4-borono-2-[¹⁸F]-fluoro-phenylalanine ([¹⁸F]FBPA) PET can be made based on lesion-to-normal ratio of [¹⁸F]FBPA accumulation. Two-dimensional data acquisition mode PET alone system, with in-plane resolution of 7.9 mm and axial resolution of 13.9 mm, was used. In the current study, we aimed to confirm the differential diagnostic capability of [¹⁸F]FBPA PET/CT with higher PET spatial resolution by three-dimensional visual inspection and by measuring mean standardized uptake value (SUVmean), maximum SUV (SUVmax), metabolic tumor volume (MTV), and total lesion (TL) [¹⁸F]FBPA uptake.

Methods

Twelve patients of glioma (9), malignant meningioma (1), hemangiopericytoma (1), and metastatic brain tumor (1) were enrolled. All had preceding radiotherapy. High-resolution three-dimensional data acquisition mode PET/CT with in-plane resolution of 4.07 mm and axial resolution of 5.41 mm was employed for imaging. Images were three-dimensionally analyzed using the PMOD software. SUVmean and SUVmax of lesion and normal brain were measured. Lesion MTV and TL FBPA uptake were calculated. The diagnostic accuracy of [¹⁸F]FBPA PET/CT in detecting recurrence (n?=?6) or necrosis (n?=?6) was verified by clinical follow-up.

Results

All parameters showed significantly higher values for tumor recurrence than for necrosis. SUVmean in recurrence was 2.95?±?0.84 vs 1.18?±?0.24 in necrosis (P?=?0.014); SUVmax in recurrence was 4.63?±?1.23 vs 1.93?±?0.44 in necrosis (P?=?0.014); MTV in recurrence was 44.92?±?28.93 mL vs 10.66?±?8.46 mL in necrosis (P?=?0.032); and mean TL FBPA uptake in recurrence was 121.01?±?50.48 g vs 12.36?±?9.70 g in necrosis (P?=?0.0029).

Conclusion

In this preliminary feasibility study, we confirmed the possibility of differentiating tumor recurrence from radiation necrosis in patients with irradiated brain tumors by [¹⁸F]FBPA PET/CT using indices of SUVmean, SUVmax, MTV, and TL ¹⁸FBPA uptake.

     

Radiomics analysis of pre-treatment [<Superscript>18</Superscript>F]FDG PET/CT for patients with metastatic colorectal cancer undergoing palliative systemic treatment

Background

The aim of this study was to assess radiomics features on pre-treatment [¹⁸F]FDG positron emission tomography (PET) as potential biomarkers for response and survival in patients with metastatic colorectal cancer (mCRC).

Methods

Patients with mCRC underwent [¹⁸F]FDG PET/computed tomography (CT) prior to first- or third-line palliative systemic treatment. Tumour lesions were semiautomatically delineated and standard uptake value (SUV), metabolically active tumour volume (MATV), total lesion glycolysis (TLG), entropy, area under the curve of the cumulative SUV-volume histogram (AUC-CSH), compactness and sphericity were obtained.

Results

Lesions of 47 patients receiving third-line systemic treatment had higher SUV_max, SUV_peak, SUV_mean, MATV and TLG, and lower AUC-CSH, compactness and sphericity compared to 52 patients receiving first-line systemic treatment. Therefore, first- and third-line groups were evaluated separately. In the first-line group, anatomical changes on CT correlated negatively with TLG (ρ?=?0.31) and MATV (ρ?=?0.36), and positively with compactness (ρ?=??0.27) and sphericity (ρ?=??0.27). Patients without benefit had higher mean entropy (p?=?0.021). Progression-free survival (PFS) and overall survival (OS) were worse with a decreased mean AUC [hazard ratio (HR) 0.86, HR 0.77] and increase in mean MATV (HR 1.15, HR 1.22), sum MATV (HR 1.14, HR 1.19), mean TLG (HR 1.16, HR 1.22) and sum TLG (HT1.12, HR1.18). In the third-line group, AUC-CSH correlated negatively with anatomical change (ρ?=?0.21). PFS and OS were worse with an increased mean MATV (HR 1.27, HR 1.68), sum MATV (HR 1.35, HR 2.04), mean TLG (HR 1.29, HR 1.52) and sum TLG (HT 1.27, HR 1.80). SUV_max and SUV_peak negatively correlated with OS (HR 1.19, HR 1.21). Cluster analysis of the 10 radiomics features demonstrated no complementary value in identifying aggressively growing lesions or patients with impaired survival.

Conclusion

We demonstrated an association between improved clinical outcome and pre-treatment low tumour volume and heterogeneity as well as high sphericity on [¹⁸F]FDG PET. Future PET imaging research should include radiomics features that incorporate tumour volume and heterogeneity when correlating PET data with clinical outcome.

     

Prospective comparison of <Superscript>68</Superscript>Ga-DOTATATE and <Superscript>18</Superscript>F-FDOPA PET/CT in patients with various pheochromocytomas and paragangliomas with emphasis on sporadic cases

Purpose

Pheochromocytomas/paragangliomas (PHEOs/PGLs) overexpress somatostatin receptors and recent studies have already shown excellent results in the localization of these tumors using ⁶⁸Ga-labeled somatostatin analogs (⁶⁸Ga-DOTA-SSA), especially in patients with germline succinate dehydrogenase subunit B gene (SDHB) mutations and head and neck PGLs (HNPGLs). The value of ⁶⁸Ga-DOTA-SSA has to be established in sporadic cases, including PHEOs. Thus, the aim of this study was to compare ⁶⁸Ga-DOTATATE PET/CT, ¹⁸F-FDOPA PET/CT, and conventional imaging in patients with various PHEOs/PGLs with a special emphasis on sporadic cases, including those located in the adrenal gland.

Design

⁶⁸Ga-DOTATATE, ¹⁸F-FDOPA PET/CT, and conventional imaging (contrast-enhanced CT and MRI with MR angiography sequences) were prospectively performed in 30 patients (8 with SDHD mutations, 1 with a MAX mutation and 21 sporadic cases) with PHEO/PGL at initial diagnosis or relapse.

Results

The patient-based sensitivities were 93 % (28/30), 97 % (29/30), and 93 % (28/30) for ⁶⁸Ga-DOTATATE PET/CT, ¹⁸F-FDOPA PET/CT, and conventional imaging, respectively. The lesion-based sensitivities were 93 % (43/46), 89 % (41/46), and 76 % (35/46) for ⁶⁸Ga-DOTATATE PET/CT, ¹⁸F-FDOPA PET/CT, and conventional imaging respectively (p?=?0.042). ⁶⁸Ga-DOTATATE PET/CT detected a higher number of HNPGLs (30/30) than ¹⁸F-FDOPA PET/CT (26/30; p?=?0.112) and conventional imaging (24/30; p?=?0.024). ⁶⁸Ga-DOTATATE PET/CT missed two PHEOs of a few millimeters in size and a large recurrent PHEO. One lesion was considered false-positive on ⁶⁸Ga-DOTATATE PET/CT and corresponded to a typical focal lesion of fibrous dysplasia on MRI. Among the 11 lesions missed by conventional imaging, 7 were detected by conventional imaging with knowledge of the PET results (4 HNPGLs, 2 LNs, and 1 recurrent PHEO).

Conclusion

⁶⁸Ga-DOTATATE PET/CT is the most sensitive tool in the detection of HNPGLs, especially SDHD-related tumors, which may be very small and fail to concentrate sufficient ¹⁸F-FDOPA. The present study further expands the use of ⁶⁸Ga-DOTATATE for all patients with HNPGLs, regardless of their genotype. ⁶⁸Ga-DOTATATE PET/CT may be inferior to ¹⁸F-FDOPA PET/CT in the detection PHEOs.