Molecular imaging of cholinergic processes in prostate cancer using <Superscript>11</Superscript>C-donepezil and <Superscript>18</Superscript>F-FEOBV

Purpose

High-grade prostate cancer (PC) displays parasympathetic neoneurogenesis. We investigated the binding of two PET tracers that visualize cholinergic nerves in PC tissue using autoradiography.

Methods

Prostatectomy tissue was subjected to autoradiography with ¹¹C-donepezil and ¹⁸F-FEOBV and correlated with Gleason scores (GS). Regions of interest on the autoradiograms were defined and quantified. Tracer binding in cancer tissue regions was compared with that in normal tissue.

Results

We included 13 patients with biopsy-verified PC. In particular, ¹¹C-donepezil uptake was higher in “high-grade” PC (GS ≥4?+?3) than in “low-grade” PC and benign hyperplasia. ¹¹C-donepezil uptake ranged from a mean of 56 % higher (GS 3?+?3) to 409 % higher (GS 4?+?4), and ¹⁸F-FEOBV uptake ranged from 67 % higher (GS 3?+?3) to 194 % higher (GS 4?+?5). The uptake of both tracers was higher in PC with a high GS than in PC with a low GS, but the difference was significant only for ¹¹C-donepezil (p?=?0.003).

Conclusion

Uptake of PET tracers binding to cholinergic nerves was markedly higher in PC with a high GS than in PC with a low GS. This finding implies that ¹¹C-donepezil PET/CT may be able to differentiate between low-grade and high-grade PC.

     

<Superscript>18</Superscript>F-FDG uptake by rectal cancer is similar in mucinous and nonmucinous histological subtypes

Purpose

PET/CT has been considered limited for the evaluation of mucinous colorectal tumors due to low ¹⁸F-FDG uptake. The aim of our study was to compare PET/CT variables in mucinous (MC) and nonmucinous (NMC) rectal adenocarcinomas.

Methods

Consecutive patients with cT2-4N0-2M0 rectal cancer included in a prospective clinical trial were reviewed. PET/CT was performed for primary baseline staging. Visual and quantitative analysis included SUVmax and SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG). PET/CT parameters were compared according to histological subtypes.

Results

Overall, 73 patients were included (18 mucinous and 55 nonmucinous). SUVmax values were similar between MC and NMC (19.7 vs. 16.6; p = 0.5). MTV and TLG values were greater in the MC group (103.9 vs. 54.1; p = 0.007 and 892.5 vs. 358.8; p = 0.020) due to larger tumor volumes of MC.

Conclusions

Metabolic parameters at baseline PET/CT for patients with rectal cancer are similar in mucinous and nonmucinous histological subtypes.

     

Diagnostic value of quantitative assessment of cardiac <Superscript>18</Superscript>F-fluoro-2-deoxyglucose uptake in suspected cardiac sarcoidosis

Objective

The identification of cardiac sarcoidosis is challenging as there is no gold standard consensually admitted for its diagnosis. The aim of this study was to evaluate the diagnostic value of the assessment of cardiac dynamic ¹⁸F-fluoro-2-deoxyglucose positron emission tomography (¹⁸F-FDG PET/CT) and net influx constant (Ki) in patients suspected of cardiac sarcoidosis.

Methods

Data obtained from 30 biopsy-proven sarcoidosis patients suspected of cardiac sarcoidosis who underwent a 50-min list-mode cardiac dynamic ¹⁸F-FDG PET/CT after a 24 h high-fat and low-carbohydrate diet were analyzed. A normalized coefficient of variation of quantitative glucose influx constant, calculated as the ratio: standard deviation of the segmental Ki (min^?1)/global Ki (min^?1) was determined using a validated software (Carimas^® 2.4, Turku PET Centre). Cardiac sarcoidosis was diagnosed according to the Japanese Ministry of Health and Welfare criteria. Receiving operating curve analysis was performed to determine sensitivity and specificity of cardiac dynamic ¹⁸F-FDG PET/CT analysis to diagnose cardiac sarcoidosis.

Results

Six out of 30 patients (20%) were diagnosed as having cardiac sarcoidosis. Myocardial glucose metabolism was significantly heterogeneous in patients with cardiac sarcoidosis who showed significantly higher normalized coefficient of variation values compared to patients without cardiac sarcoidosis (0.513?±?0.175 vs. 0.205?±?0.081; p?=?0.0007). Using ROC curve analysis, we found a cut-off value of 0.38 for the diagnosis of cardiac sarcoidosis with a sensitivity of 100% and a specificity of 91%.

Conclusions

Our results suggest that quantitative analysis of cardiac dynamic ¹⁸F-FDG PET/CT could be a useful tool for the diagnosis of cardiac sarcoidosis.

     

<Superscript>18</Superscript>F-FDG and <Superscript>18</Superscript>F-FLT PET/CT imaging in the characterization of mediastinal lymph nodes

Purpose

There is currently no single modality for accurate characterization of enlarged mediastinal lymph nodes into benign or malignant. Recently ¹⁸F-fluorothymidine (FLT) has been used as a proliferation marker. In this prospective study, we examined the role of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) and ¹⁸F-FLT PET/CT in categorizing mediastinal lymph nodes as benign or malignant.

Materials and methods

A total of 70 consecutive patients with mediastinal lymphadenopathy detected on computed tomography (CT) or chest radiograph underwent whole body ¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT (within 1 week of each other). Lymph nodal tracer uptake was determined by calculation of standardized uptake value (SUV) with both the tracers. Results of PET/CT were compared with histopathology of the lymph nodes.

Results

Histopathology results showed thirty-seven patients with sarcoidosis, seven patients with tuberculosis, nine patients with non-small cell lung cancer, five patients with Hodgkin’s lymphoma and twelve patients with non-Hodgkin’s lymphoma. The mean FDG SUV_max of sarcoidosis, tuberculosis, Hodgkin’s and non-Hodgkin’s lymphoma was 12.7, 13.4, 8.2, and 8.8, respectively, and the mean FLT SUV_max was 6.0, 5.4, 4.4, and 3.8, respectively. It was not possible to characterize mediastinal lymphadenopathy as benign or malignant solely based on FDG SUV_max values (p > 0.05) or FLT SUV_max values (p > 0.05). There was no significant difference in FDG uptake (p > 0.9) or FLT uptake (p > 0.9) between sarcoidosis and tuberculosis. In lung cancer patients, the FDG SUV_max and FLT SUV_max of those lymph nodes with tumor infiltration on biopsy was 6.7 and 3.9, respectively, and those without nodal infiltration was 6.4 and 3.7, respectively, and both the tracers were not able to characterize the nodal status as malignant or benign (p > 0.05).

Conclusion

Though ¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT reflect different aspects of biology, i.e., proliferation and metabolism, respectively, neither tracer could provide satisfactory categorization of benign and malignant lymph nodes. The results of this study clearly suggest that differentiation of mediastinal nodes into benign and malignant solely based on SUV_max values cannot be relied upon, especially in settings where tuberculosis and sarcoidosis are common.

     

<Superscript>68</Superscript>Ga-DOTATATE PET/CT in recurrent medullary thyroid carcinoma: a lesion-by-lesion comparison with <Superscript>111</Superscript>In-octreotide SPECT/CT and conventional imaging

Purpose

The aim of this study was to prospectively compare the detection rate of ⁶⁸Ga-DOTATATE PET-CT with ¹¹¹In-octreotide SPECT-CT and conventional imaging (CI) in medullary thyroid carcinoma (MTC) patients with increased calcitonin (Ctn) levels but negative CI after thyroidectomy.

Methods

Fifteen patients with raised Ctn levels and/or CI evidence of recurrence underwent ⁶⁸Ga-DOTATATE PET-CT, ¹¹¹In-octreotide SPECT-CT and CI. Histopathology, CI and biochemical/clinical/imaging follow-up were used as the reference standard. PET/CT, SPECT/CT and CI were compared in a lesion-based and organ-based analysis.

Results

PET/CT evidenced recurrence in 14 of 15 patients. There were 13 true positive (TP), 1 true negative (TN), 1 false positive (FP) and no false negative (FN) cases, resulting in a sensitivity and accuracy of 100% and 93%. SPECT/CT was positive in 6 of 15 cases. There were 6 TP, 2 TN, 7 FN and no FP cases, resulting in a sensitivity of 46% and accuracy of 53%. CI procedures detected tumor lesions in 14 of 15 patients. There were 13 TP, 1TN, 1 FP and no FN cases with a sensitivity of 100% and accuracy of 93%.A significantly higher number of lesions was detected by PET/CT (112 lesions, p = 0.005) and CI (109 lesions, p = 0.005) in comparison to SPECT/CT (16 lesions). There was no significant difference between PET/CT and CI for the total number of detected lesions (p = 0.734). PET/CT detected more lesions than SPECT/CT regardless of the organ. PET/CT detected more bone lesions but missed some neck nodal metastases evidenced by CI. The number of lesions per region demonstrated by PET/CT and CI were similar in the other sites.

Conclusion

⁶⁸Ga-DOTATATE PET/CT is superior to ¹¹¹In-octreotide SPECT/CT for the detection of recurrent MTC demonstrating a significantly higher number of lesions. ⁶⁸Ga-DOTATATE PET/CT showed a superior detection rate compared to CI in demonstrating bone metastases.

     

Assessing the role of <Superscript>18</Superscript>F-FDG PET and <Superscript>18</Superscript>F-FDG PET/CT in the diagnosis of soft tissue musculoskeletal malignancies: a systematic review and meta-analysis

Purpose

Twelve years ago a meta-analysis evaluated the diagnostic performance of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in assessing musculoskeletal soft tissue lesions (MsSTL). Currently, PET/CT has substituted PET imaging; however, there has not been any published meta-analysis on the use of PET/CT or a comparison of PET/CT with PET in the diagnosis of MsSTL. Therefore, we conducted a meta-analysis to identify the current diagnostic performance of ¹⁸F-FDG PET/CT and determine if there is added value when compared to PET.

Methods

A systematic review of English articles was conducted, and MEDLINE PubMed, the Cochrane Library, and Embase were searched from 1996 to March 2015. Studies exploring the diagnostic accuracy of ¹⁸F-FDG PET/CT (or dedicated PET) compared to histopathology in patients with MsSTL undergoing investigation for malignancy were included.

Results

Our meta-analysis included 14 articles composed of 755 patients with 757 soft tissue lesions. There were 451 (60 %) malignant tumors and 306 benign lesions. The ¹⁸F-FDG PET/CT (and dedicated PET) mean sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for diagnosing MsSTL were 0.96 (0.90, 1.00), 0.77 (0.67, 0.86), 0.88 (0.85, 0.91), 0.86 (0.78, 0.94), and 0.91 (0.83, 0.99), respectively. The posterior mean (95 % highest posterior density interval) for the AUC was 0.92 (0.88, 0.96). PET/CT had higher specificity, accuracy, and positive predictive value when compared to a dedicated PET (0.85, 0.89, and 0.91 vs 0.71, 0.85, and 0.82, respectively).

Conclusion

¹⁸F-FDG PET/CT and dedicated PET are both highly accurate in the diagnosis of MsSTL. PET/CT is more accurate and specific and has a higher positive predictive value than PET.

     

Prospective evaluation of <Superscript>18</Superscript>F-FACBC PET/CT and PET/MRI versus multiparametric MRI in intermediate- to high-risk prostate cancer patients (FLUCIPRO trial)

Purpose

The purpose of this study was to evaluate ¹⁸F-FACBC PET/CT, PET/MRI, and multiparametric MRI (mpMRI) in detection of primary prostate cancer (PCa).

Methods

Twenty-six men with histologically confirmed PCa underwent PET/CT immediately after injection of 369 ± 10 MBq ¹⁸F-FACBC (fluciclovine) followed by PET/MRI started 55 ± 7 min from injection. Maximum standardized uptake values (SUV_max) were measured for both hybrid PET acquisitions. A separate mpMRI was acquired within a week of the PET scans. Logan plots were used to calculate volume of distribution (V_T). The presence of PCa was estimated in 12 regions with radical prostatectomy findings as ground truth. For each imaging modality, area under the curve (AUC) for detection of PCa was determined to predict diagnostic performance. The clinical trial registration number is NCT02002455.

Results

In the visual analysis, 164/312 (53%) regions contained PCa, and 41 tumor foci were identified. PET/CT demonstrated the highest sensitivity at 87% while its specificity was low at 56%. The AUC of both PET/MRI and mpMRI significantly (p < 0.01) outperformed that of PET/CT while no differences were detected between PET/MRI and mpMRI. SUV_max and V_T of Gleason score (GS) >3 + 4 tumors were significantly (p < 0.05) higher than those for GS 3 + 3 and benign hyperplasia. A total of 442 lymph nodes were evaluable for staging, and PET/CT and PET/MRI demonstrated true-positive findings in only 1/7 patients with metastatic lymph nodes.

Conclusions

Quantitative ¹⁸F-FACBC imaging significantly correlated with GS but failed to outperform MRI in lesion detection. ¹⁸F-FACBC may assist in targeted biopsies in the setting of hybrid imaging with MRI.

     

Recurrent prostate cancer detection with <Emphasis Type="Italic">anti</Emphasis>-3-[<Superscript>18</Superscript>F]FACBC PET/CT: comparison with CT

Purpose

To compare the diagnostic performance of the synthetic amino acid analogue PET radiotracer anti-3-[¹⁸F]FACBC (fluciclovine) with that of CT in the detection of recurrent prostate carcinoma.

Methods

This was a retrospective analysis of 53 bone scan-negative patients with suspected recurrent prostate carcinoma who underwent fluciclovine PET/CT and routine clinical CT within 90 days of each other. The correlation between imaging findings and histology and clinical follow-up was evaluated. Positivity rates and diagnostic performance were calculated for fluciclovine PET/CT and CT.

Results

Of 53 fluciclovine PET/CT and 53 CT examinations, 41 (77.4 %) and 10 (18.9 %), respectively, had positive findings for recurrent disease. Positivity rates were higher with fluciclovine PET/CT than with CT at all prostate-specific antigen (PSA) levels, PSA doubling times and original Gleason scores. In the prostate/bed, fluciclovine PET/CT was true-positive in 31 and CT was true-positive in 4 of 51 patients who met the reference standard. In extraprostatic regions, fluciclovine PET/CT was true-positive in 12 and CT was true-positive in 3 of 41 patients who met the reference standard. Of the 43 index lesions used to prove positivity, 42 (97.7 %) had histological proof. In 51 patients with sufficient follow-up to calculate diagnostic performance in the prostate/bed, fluciclovine PET/CT demonstrated a sensitivity of 88.6 %, a specificity of 56.3 %, an accuracy of 78.4 %, a positive predictive value (PPV) of 81.6 %, and a negative predictive value (NPV) of 69.2 %; the respective values for CT were 11.4 %, 87.5 %, 35.3 %, 66.7 % and 31.1 %. In 41 patients with sufficient follow-up to calculate diagnostic performance in extraprostatic regions, fluciclovine PET/CT demonstrated a sensitivity of 46.2 %, a specificity of 100 %, an accuracy of 65.9 %, a PPV of 100 %, and an NPV of 51.7 %; the respective values for CT were 11.5 %, 100 %, 43.9 %, 100 % and 39.5 %.

Conclusion

The diagnostic performance of fluciclovine PET/CT in recurrent prostate cancer is superior to that of CT and fluciclovine PET/CT provides better delineation of prostatic from extraprostatic recurrence.

     

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.

     

<Superscript>18</Superscript>F-Fluorocholine PET/CT for early response assessment in patients with metastatic castration-resistant prostate cancer treated with enzalutamide

Purpose

We investigated the role of ¹⁸F-methylcholine (FCH) PET/CT in the early evaluation of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide.

Methods

The study group comprised 36 patients with a median age of 72 years (range 48–90 years) who were treated with enzalutamide 160 mg once daily after at least one chemotherapeutic regimen with docetaxel. Patients were evaluated monthly for serological prostate-specific antigen (PSA) response. FCH PET/CT was performed at baseline and repeated after 3–6 weeks. Univariate and multivariate Cox regression models addressed potential predictors of progression-free survival (PFS) and overall survival (OS).

Results

At a median follow-up of 24.2 months (range 1.8–27.3 months), 34 patients were evaluable for early FCH PET/CT evaluation of response, and of these 17 showed progressive disease (PD) and 17 had stable disease or a partial response. A decrease in PSA level of more than 50 % was observed in 21 patients. Early FCH PET/CT PD predicted radiological PD 3 months in advance of CT in 12 of 18 patients (66 %) and was discordant with the decrease in PSA level in 13 patients. In 6 of these, biochemical PD was confirmed in 2 months. In multivariate analysis, only decrease in PSA level and FCH PET/CT were significant predictors of PFS (p?=?0.0005 and p?=?0.029, respectively), whereas decrease in PSA level alone was predictive of OS (p?=?0.007).

Conclusion

This is one of the first studies to evaluate the role of FCH PET/CT as an early predictor of outcome in mCRPC patients treated with enzalutamide. Our preliminary results suggest that the combination of FCH PET/CT and decrease in PSA level could be a valid tool to predict PFS in mCRPC patients. PSA remains the single most important prognostic factor, while FCH PET/CT does not add more information on OS beyond that obtained from PSA. Further studies in larger populations are needed to confirm these data and to clarify the role of FCH PET/CT in predicting response to enzalutamide in mCRPC patients.

     

<Superscript>18</Superscript>F-FDG PET in small-cell cervical cancer: a prospective study with long-term follow-up

Purpose

Small-cell cervical cancer (SCCC) is rare and prone to metastasize. We conducted a prospective study to evaluate the role of ¹⁸F-FDG PET in the management of this aggressive malignancy.

Methods

Patients with untreated primary, histologically confirmed SCCC were enrolled. ¹⁸F-FDG PET (or PET/CT) was performed immediately after MRI or CT, for primary staging, monitoring response to treatment or restaging when there was suspicion of recurrence. The clinical impact of PET was determined on a scan basis.

Results

A total of 25 patients were recruited and 43 PET scans were performed. The PET images were obtained for primary staging (25 patients), monitoring response (10 patients) and restaging when there was suspicion of recurrence (8 patients). The median follow-up time in event-free patients was 109.3 months (range 97.5 – 157.7 months). A positive impact of PET was found in 8 (18.6 %) of the 43 scans, which included detection of additional regions of distal lymph node (LN) metastasis (one primary staging scan, two restaging scans), bone metastasis (two primary staging scans, one monitoring response scan), and exclusion of false-positive lesions on MRI (one primary staging scan, one restaging scan). On the other hand, one negative impact was recorded as one false-positive lesion on a restaging PET scan. One positive impact was noted for monitoring response (bone metastasis). The impact of three scans was indeterminate. The positive impact of down-staging in avoiding overtreatment but finding additional distal LN (except one on restaging) or bone metastases had no beneficial effect on long-term survival.

Conclusion

The results of this preliminary study suggest that PET is useful in the management of SCCC. PET could have more value in detecting occult metastases if future novel therapies are able to offer better control of extensive SCCC.

     

Evaluation of <Superscript>68</Superscript>Ga-DOTA-TOC PET/CT for the detection of duodenopancreatic neuroendocrine tumors in patients with MEN1

Context

Somatostatin receptor scintigraphy with ¹¹¹In-pentetreotide (SRS) is used to detect duodenopancreatic neuroendocrine tumors (dpNETs) in multiple endocrine neoplasia type 1 (MEN1). However, SRS has limited sensitivity for this purpose. Positron emission tomography/computed tomography (PET/CT) with ⁶⁸Ga-DOTA-TOC has a higher rate of sporadic dpNETs detection than SRS but there is little data for dpNETs detection in MEN1.

Purpose

To compare the performances of ⁶⁸Ga-DOTA-TOC PET/CT, SRS and contrast-enhanced computed tomography (CE-CT) to diagnose dpNETs in MEN1.

Design and setting

Single-institution prospective comparative study

Patients and methods

Nineteen consecutive MEN1 patients (aged 47?±?13 years) underwent ⁶⁸Ga-DOTA-TOC PET/CT, SRS, and CE-CT within 2 months in random order. Blinded readings of images were performed separately by experienced physicians. Unblinded analysis of CE-CT, combined with additional magnetic resonance imaging, endoscopic-ultrasound, ¹⁸F-2-fluoro-deoxy-d-glucose (¹⁸F-FDG) PET/CT or histopathology results served as reference standard for dpNETs diagnosis.

Results

The sensitivity of ⁶⁸Ga-DOTA-TOC PET/CT, SRS, and CE-CT was 76, 20, and 60 %, respectively (p?<?0.0001). All the true-positive lesions detected by SRS were also depicted on ⁶⁸Ga-DOTA-TOC PET/CT. ⁶⁸Ga-DOTA-TOC PET/CT detected lesions of smaller size than SRS (10.7?±?7.6 and 15.2?±?5.9 mm, respectively, p?<?0.03). False negatives of ⁶⁸Ga-DOTA-TOC PET/CT included small dpNETs (<10 mm) and ¹⁸F-FDG PET/CT positive aggressive dpNETs. No false positives were recorded. In addition, whole-body mapping with ⁶⁸Ga-DOTA-TOC PET/CT identified extra-abdominal MEN1-related tumors including one neuroendocrine thymic carcinoma identified by the three imaging procedures, one bronchial carcinoid undetected by CE-CT and three meningiomas undetected by SRS.

Conclusions

Owing to higher diagnostic performance, ⁶⁸Ga-DOTA-TOC PET/CT (or alternative ⁶⁸Ga-labeled somatostatin analogues) should replace ¹¹¹In-pentetreotide in the investigation of MEN1 patients.

     

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.

     

<Superscript>18</Superscript>F-DOPA PET/CT in the diagnosis and localization of persistent medullary thyroid carcinoma

Purpose

To evaluate the performance of ¹⁸F-l-dihydroxyphenylalanine (¹⁸F-DOPA) PET/CT in the detection of locoregional and distant medullary thyroid carcinoma (MTC) metastases and to compare imaging findings with histological data.

Methods

We retrospectively evaluated 86 MTC patients with persistently high serum calcitonin levels after initial surgery who had undergone ¹⁸F-DOPA PET/CT between January 2007 and December 2014 in two referral centres. They were followed up for at least 6 months after the PET/CT assessment. The results were compared with histological data or with the findings obtained during follow-up using a complementary imaging modality.

Results

¹⁸F-DOPA PET/CT was positive in 65 of the 86 patients, corresponding to a patient-based sensitivity of 75.6 %. Distant metastatic disease (M1) was seen in 29 patients including 11 with previously unknown metastases revealed only by PET/CT. Among the 36 patients without distant metastatic spread, 25 had nodal involvement limited to the neck, and 10 of these 25 patients underwent reoperation. The lymph node compartment-based sensitivity of ¹⁸F-DOPA PET/CT was 100 % in the two institutions but lesion-based sensitivity was only 24 %. Preoperative and postoperative median calcitonin levels were 405 pg/mL (range 128 – 1,960 pg/mL) and 259 pg/mL (range 33 – 1,516 pg/mL), respectively. None of the patients achieved normalization of serum calcitonin after reoperation.

Conclusion

¹⁸F-DOPA PET/CT enables early diagnosis of a significant number of patients with distant metastasis. It has a limited sensitivity in the detection of residual disease but provides high performance for regional analysis. A surgical compartment-oriented approach could be the approach of choice whatever the number of nodes revealed by ¹⁸F-DOPA PET/CT.

     

Role of <Superscript>68</Superscript>Ga somatostatin receptor PET/CT in the detection of endogenous hyperinsulinaemic focus: an explorative study

Purpose

To explore the role of ⁶⁸Ga-DOTATATE/DOTATOC PET/CT (SR PET/CT) in patients with suspicion of or histopathologically proven pancreatogenic hyperinsulinaemic hypoglycaemia.

Methods

We included 13 patients with histopathologically proven or a high clinical suspicion of pancreatogenic hyperinsulinaemia. All the patients underwent a SR PET/CT scan. The results were correlated with histopathological findings. Normalization of blood glucose levels after resection of the pancreatic lesion, as well as a cytological and/or pathological diagnosis of insulinoma, was considered the diagnostic gold standard for insulinoma. The diagnosis of nesidioblastosis was based on exclusion of an insulinoma and conclusive pathological examination of a segment of the pancreas. Malignant insulinoma was defined as the presence of locoregional or distant metastases.

Results

Based on histopathology, 13 patients were found to have pancreatic hyperinsulinaemia: two patients had malignant insulinoma, eight had nonmetastasized insulinoma, and three had nesidioblastosis. SR PET was positive in 11 of the 13 patients (84.6 %) with a final diagnosis of endogenous pancreatic hypoglycaemia. Histopathological staining confirmed 16 foci of hyperinsulinism (insulin positivity). SR PET detected 14 of the 16 lesions, resulting in a sensitivity of 87 %. One intrapancreatic spleen was falsely diagnosed as insulinoma focus on SR PET, resulting in positive predictive value of 93.3 %. Immunohistochemical staining of somatostatin receptor (SSR) subtype 2a was available in ten specimens: two nesidioblastosis, and seven benign and one malignant insulinoma. Eight out of the ten specimens (80 %) stained strongly to moderately positive. Seven of the eight SSR2a-positive lesions were picked up on SR PET. Based on the results of SR PET/CT, nine patients achieved complete remission of the hypoglycaemic events during follow-up.

Conclusion

This explorative study suggests that SR PET in combination with CT may play a significant role in the detection and management of patients with pancreatogenic hyperinsulinaemic hypoglycaemia. A large proportion of insulinomas express SSR2a, and a larger study is needed to fully assess the diagnostic accuracy of SR PET in patients with insulinoma and nesidioblastosis compared with current localizing studies used in clinical practice.

     

<Superscript>18</Superscript>F-FDG PET/CT for the Diagnosis of Malignant and Infectious Complications After Solid Organ Transplantation

Purpose

Infection and malignancy represent two common complications after solid organ transplantation, which are often characterized by poorly specific clinical symptomatology. Herein, we have evaluated the role of ¹⁸F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) in this clinical setting.

Methods

Fifty-eight consecutive patients who underwent FDG PET/CT after kidney, lung or heart transplantation were included in this retrospective analysis. Twelve patients underwent FDG PET/CT to strengthen or confirm a diagnostic suspicion of malignancies. The remaining 46 patients presented with unexplained inflammatory syndrome, fever of unknown origin (FUO), CMV or EBV seroconversion during post-transplant follow-up without conclusive conventional imaging. FDG PET/CT results were compared to histology or to the finding obtained during a clinical/imaging follow-up period of at least 6 months after PET/CT study.

Results

Positive FDG PET/CT results were obtained in 18 (31 %) patients. In the remaining 40 (69 %) cases, FDG PET/CT was negative, showing exclusively a physiological radiotracer distribution. On the basis of a patient-based analysis, FDG PET/CT’s sensitivity, specificity, PPV and NPV were respectively 78 %, 90 %, 78 % and 90 %, with a global accuracy of 86 %. FDG PET/CT was true positive in 14 patients with bacterial pneumonias (n?=?4), pulmonary fungal infection (n?=?1), histoplasmosis (n?=?1), cutaneous abscess (n?=?1), inflammatory disorder (sacroiliitis) (n?=?1), lymphoma (n?=?3) and NSCLC (n?=?3). On the other hand, FDG PET/CT failed to detect lung bronchoalveolar adenocarcinoma, septicemia, endocarditis and graft-versus-host disease (GVHD), respectively, in four patients. FDG PET/CT contributed to adjusting the patient therapeutic strategy in 40 % of cases.

Conclusions

FDG PET/CT emerges as a valuable technique to manage complications in the post-transplantation period. FDG PET/CT should be considered in patients with severe unexplained inflammatory syndrome or FUO and inconclusive conventional imaging or to discriminate active from silent lesions previously detected by conventional imaging particularly when malignancy is suspected.

     

Prospective head-to-head comparison of <Superscript>11</Superscript>C-choline-PET/MR and <Superscript>11</Superscript>C-choline-PET/CT for restaging of biochemical recurrent prostate cancer

Purpose

Whole-body integrated ¹¹C-choline PET/MR might provide advantages compared to ¹¹C-choline PET/CT for restaging of prostate cancer (PC) due to the high soft-tissue contrast and the use of multiparametric MRI, especially for detection of local recurrence and bone metastases.

Materials and methods

Ninety-four patients with recurrent PC underwent a single-injection/dual-imaging protocol with contrast-enhanced PET/CT followed by fully diagnostic PET/MR. Imaging datasets were read separately by two reader teams (team 1 and 2) assessing the presence of local recurrence, lymph node and bone metastases in predefined regions using a five-point scale. Detection rates were calculated. The diagnostic performance of PET/CT vs. PET/MR was compared using ROC analysis. Inter-observer and inter-modality variability, radiation exposure, and mean imaging time were evaluated. Clinical follow-up, imaging, and/or histopathology served as standard of reference (SOR).

Results

Seventy-five patients qualified for the final image analysis. A total of 188 regions were regarded as positive: local recurrence in 37 patients, 87 regions with lymph node metastases, and 64 regions with bone metastases. Mean detection rate between both readers teams for PET/MR was 84.7% compared to 77.3% for PET/CT (p > 0.05). Local recurrence was identified significantly more often in PET/MR compared to PET/CT by team 1. Lymph node and bone metastases were identified significantly more often in PET/CT compared to PET/MR by both teams. However, this difference was not present in the subgroup of patients with PSA values ≤2 ng/ml.Inter-modality and inter-observer agreement (K > 0.6) was moderate to substantial for nearly all categories. Mean reduction of radiation exposure for PET/MR compared to PET/CT was 79.7% (range, 72.6–86.2%). Mean imaging time for PET/CT was substantially lower (18.4 ± 0.7 min) compared to PET/MR (50.4 ± 7.9 min).

Conclusions

¹¹C-choline PET/MR is a robust imaging modality for restaging biochemical recurrent PC and interpretations between different readers are consistent. It provides a higher diagnostic value for detecting local recurrence compared to PET/CT with the advantage of substantial dose reduction. Drawbacks of PET/MR are a substantially longer imaging time and a slight inferiority in detecting bone and lymph node metastases in patients with PSA values >2 ng/ml. Thus, we suggest the use of ¹¹C-choline PET/MR especially for patients with low (≤2 ng/ml) PSA values, whereas PET/CT is preferable in the subgroup with higher PSA values.

     

Role of <Superscript>18</Superscript>F-FDG PET/CT in patients affected by Langerhans cell histiocytosis

Purpose

Langerhans cell histiocytosis (LCH) is a rare hematological disorder for which the utility of¹⁸F-FDG PET/CT is unclear. Our aim was to explore the metabolic features of LCH and the possible role of¹⁸F-FDG PET/CT in LCH evaluation.

Materials and methods

We found 17 patients with histologically proven LCH who underwent 17¹⁸F-FDG PET/CT scans for staging and 42 scans for restaging/follow-up purposes. PET/CT results were compared with those obtained from other conventional imaging modalities (bone scintigraphy, plain radiogram, computed tomography, magnetic resonance).

Results

¹⁸F-FDG PET/CT was positive in 15/17 patients, and it detected 36/37 lesions; all bone and extraskeletal lesions, except for a cecal lesion, were¹⁸F-FDG-avid. Only 1/4 of the patients with lung LCH had hypermetabolic lesions. The average SUV_max of the FDG-avid lesions was 7.3 ± 6.7, the average lesion-to-liver SUV_max ratio was 3.4 ± 2.5, and the average lesion-to-blood pool SUV_max ratio was 4 ± 3.2. In comparison to other imaging methods,¹⁸F-FDG PET/CT detected additional lesions or was able to evaluate treatment response earlier in 33/74 cases; it was confirmatory in 38/74 and detected fewer lesions in 3/74 (all three with lung LCH).

Conclusions

¹⁸F-FDG PET/CT seems to be useful for evaluating LCH when compared to conventional imaging, except in pulmonary cases. It can be used both for staging and restaging purposes.

     

Incidental focal <Superscript>18</Superscript>F-FDG uptake in the frontal process of the maxilla on PET/CT: prevalence and clinical significance

Objective

We investigated the prevalence and clinical significance of incidental focal ¹⁸F-FDG uptake in the frontal process of the maxilla, mimicking malignancy on PET/CT.

Methods

From a total of 32,834 patients who underwent ¹⁸F-FDG PET/CT, patients with focal uptake in the frontal process of the maxilla were selected by a database search. For those patients, medical records including relevant imaging studies were reviewed.

Results

Thirty-nine patients (0.12 %) demonstrated focal uptake on PET/CT. On CT of PET/CT, all lesions showed ground-glass attenuation with or without bony expansion, consistent with fibrous dysplasia. When comparing previous PET/CT, follow-up PET/CT, and CT, a significant difference in degree of ¹⁸F-FDG uptake was noted, with no associated change in the size of maxillary lesions. There were no patients who had symptoms or signs related to maxillary lesions during follow-up.

Conclusion

Focal ¹⁸F-FDG uptake in the frontal process of the maxilla is a rare, incidental, and persistent finding with variable uptake and can represent a benign condition.

     

Prognostic value of PET/CT with <Superscript>18</Superscript>F-fluoroazomycin arabinoside for patients with head and neck squamous cell carcinomas receiving chemoradiotherapy

Objective

The prognostic value of positron emission tomography/computed tomography (PET/CT) with ¹⁸F-fluoroazomycin arabinoside (FAZA) was evaluated in patients with head and neck squamous cell carcinoma (HNSCC) who underwent chemoradiotherapy (CRT).

Methods

Twenty-nine patients with head and neck cancer underwent FAZA PET/CT before treatment. Data acquisition started 2 h after FAZA administration. In 26 patients with squamous cell carcinoma, FAZA uptakes by the primary lesions (tumor–muscle ratio in primary lesion: Pr T/M) and by the lymph node metastases (tumor–muscle ratio in lymph node metastasis) were compared with various clinical parameters. For the HNSCC patients who completed CRT protocol (n = 23), those who experienced disease progression were compared with those who did not experience disease progression with respect to the clinical and PET parameters. The prognostic values of the clinical and PET parameters were then evaluated with regard to progression-free survival (PFS).

Results

Pr T/M positively correlated with the lesion’s maximum diameter, and it was significantly higher in stage IV lesions compared with stage I–III lesions. No significant differences were observed between the patients who experienced disease progression and those who did not, with respect to the clinical parameters. The average Pr T/M tended to be higher in patients with disease progression, although the differences were not statistically significant (p = 0.086). Kaplan–Meier analysis with log-rank tests indicated that Pr T/M was an only significant predictor of PFS among PET and clinical parameters evaluated (p = 0.010).

Conclusions

FAZA uptake by the primary lesion was a significant prognostic indicator in HNSCC patients undergoing CRT. Hence, FAZA PET/CT may provide useful information in the management of HNSCC patients treated with CRT. Registration number of clinical trial’s registry: UMIN000003440.