Quantitative <Superscript>18</Superscript>F-DOPA PET/CT in pheochromocytoma: the relationship between tumor secretion and its biochemical phenotype

Introduction

¹⁸F-FDOPA illustrates the properties of uptake and storage of catecholamines in pheochromocytomas (PHEOs). Until now, the relationship between ¹⁸F-FDOPA quantitative parameters and a PHEO secretory profile has not been specifically evaluated.

Materials and methods

Fifty-six patients (56% females, median age: 47.5 yrs) with non-metastatic PHEO, evaluated by ¹⁸F-FDOPA PET/CT, were included in this retrospective study. Forty-five patients had negative genetic testing (80.4%); five patients (8.9%) had RET, two patients (3.6%) had SDHB, two had SDHD (3.6%), one patient (1.8%) had NF1, and one patient had a VHL (1.8%) mutation. Correlation between ¹⁸F-FDOPA metabolic parameters (tumor SUVmax, tumor SUVmean, tumor SUVmax/liver SUVmax, MTV 42%, total lesion uptake), urinary metanephrines (MNs), and plasma chromogranin A (CgA) were evaluated.

Results

All patients had positive ¹⁸F-FDOPA PET/CT. On univariate analysis, there was a strong correlation between all metabolic parameters and urinary MNs and plasma chromogranin A (CgA). The highest correlations were observed between total lesion (TL) uptake and the value of urinary MNs regardless of their nature (p = 8.10^?15 and r = 0.80) and between MTV 42% and plasma CgA levels (p = 2.10^?9, r = 0.74). On multivariate analysis, the correlation of uptake parameters and CgA levels did not persist further due to the relation of CgA and tumor diameter. A correlation between TL uptake and the normetanephrine/metanephrine ratio (NMN/MN) was also found, a finding that was in accordance with in vitro studies, which were found to have a higher catecholamine content in epinephrine producing PHEOs.

Conclusion

This retrospective study shows a correlation between ¹⁸F-FDOPA uptake, especially using TL uptake, urinary MNs, and a PHEO biochemical phenotype. This illustrates that beyond its localization value, ¹⁸F-FDOPA PET further enables PHEO characterization at a specific metabolic level.

     

PET/CT comparing <Superscript>68</Superscript>Ga-DOTATATE and other radiopharmaceuticals and in comparison with CT/MRI for the localization of sporadic metastatic pheochromocytoma and paraganglioma

Purpose

Pheochromocytomas/paragangliomas (PPGLs) and their metastases are tumors that predominantly express somatostatin receptor 2 (SSR2). ⁶⁸Ga-DOTA(0)-Tyr(3)-octreotate (⁶⁸Ga-DOTATATE) is a PET radiopharmaceutical with both high and selective affinity for SSRs. The purpose of this study was to evaluate the utility of ⁶⁸Ga-DOTATATE in comparison with other specific and nonspecific radiopharmaceuticals recommended in the current guidelines for the localization of metastatic sporadic PPGL by PET/CT.

Methods

This prospective study included 22 patients (15 men, 7 women; aged 50.0?±?13.9 years) with confirmed metastatic PPGL, a negative family history for PPGL, and negative genetic testing, who underwent ⁶⁸Ga-DOTATATE, ¹⁸F-fluoro-2-deoxy-D-glucose (¹⁸F-FDG) PET/CT, and CT/MRI. Only 12 patients underwent an additional ¹⁸F-fluorodihydroxyphenylalanine (¹⁸F-FDOPA) PET/CT scan and only 11 patients underwent an additional ¹⁸F-fluorodopamine (¹⁸F-FDA) PET/CT scan. The rates of detection of metastatic lesions were compared among all the imaging studies. A composite of all functional and anatomical imaging studies served as the imaging comparator.

Results

⁶⁸Ga-DOTATATE PET/CT showed a lesion-based detection rate of 97.6 % (95 % confidence interval, CI, 95.8 – 98.7 %). ¹⁸F-FDG PET/CT, ¹⁸F-FDOPA PET/CT, ¹⁸F-FDA PET/CT, and CT/MRI showed detection rates of 49.2 % (CI 44.5 – 53.6 %; p?<?0.01), 74.8 % (CI 69.0 – 79.9 %); p?<?0.01), 77.7 % (CI 71.5 – 82.8 %; p?<?0.01), and 81.6 % (CI 77.8 – 84.8 %; p?<?0.01), respectively.

Conclusion

The results of this study demonstrate the superiority of ⁶⁸Ga-DOTATATE PET/CT in the localization of sporadic metastatic PPGLs compared to all other functional and anatomical imaging modalities, and suggest modification of future guidelines towards this new imaging modality.

     

Head-to-head comparison between <Superscript>18</Superscript>F-FDOPA PET/CT and MR/CT angiography in clinically recurrent head and neck paragangliomas

Purpose

Head and neck paragangliomas (HNPGLs) can relapse after primary treatment. Optimal imaging protocols have not yet been established for posttreatment evaluation. The aim of the present study was to assess the diagnostic value of ¹⁸F-FDOPA PET/CT and MR/CT angiography (MRA/CTA) in HNPGL patients with clinical relapse during their follow-up.

Methods

Sixteen consecutive patients presenting with local pain, tinnitus, dysphagia, hoarse voice, cranial nerve involvement, deafness, or retrotympanic mass appearing during follow-up after the initial treatment of HNPGLs were retrospectively evaluated. Patients underwent both ¹⁸F-FDOPA PET/CT and MRA (15 patents) or CTA (1 patent). Both methods were first assessed under blinded conditions and afterwards correlated. Head and neck imaging abnormalities without histological confirmation were considered true-positive results based on a consensus between radiologists and nuclear physicians and on further ¹⁸F-FDOPA PET/CT and/or MRA.

Results

¹⁸F-FDOPA PET/CT and MRA/CTA were concordant in 14 patients and in disagreement in 2 patients. ¹⁸F-FDOPA PET/CT and MRA/CTA identified, respectively, 12 and 10 presumed recurrent HNPGLs in 12 patients. The two lesions diagnosed by PET/CT only were confirmed during follow-up by otoscopic examination and MRA performed 29 and 17 months later. ¹⁸F-FDOPA PET/CT images were only slightly influenced by the posttreatment sequelae, showing a better interobserver reproducibility than MRA/CTA. Finally, in 2 of the 16 studied patients, ¹⁸F-FDOPA PET/CT detected two additional synchronous primary HNPGLs.

Conclusion

¹⁸F-FDOPA PET/CT is highly sensitive in posttreatment evaluation of patients with HNPGLs, and also offers better interobserver reproducibility than MRA/CTA and whole-body examination. We therefore suggest that ¹⁸F-FDOPA PET/CT is performed as the first diagnostic imaging modality in symptomatic patients with suspicion of HNPGL relapse after primary treatment when ⁶⁸Ga-labeled somatostatin analogues are not available.

     

<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.

     

<Superscript>18</Superscript>F-fluorodihydroxyphenylalanine PET/CT in pheochromocytoma and paraganglioma: relation to genotype and amino acid transport system L

Purpose

F-FDOPA is a highly sensitive and specific radiopharmaceutical for pheochromocytoma and paraganglioma (PPGL) imaging. However, ¹⁸F-FDOPA might be falsely negative in these tumors, especially those related to mutations in succinate dehydrogenase genes (SDHx). The aim of the present study was to evaluate the relationship between expression of L-DOPA transporters and ¹⁸F-FDOPA PET imaging results in PPGL.

Methods

From 2007 to 2015, 175 patients with non-metastatic PPGL were evaluated by ¹⁸F-FDOPA PET/CT for initial diagnosis/staging and follow-up. ¹⁸F-FDOPA PET/CT was considered as falsely negative for at least one lesion in 10/126 (8%) patients (two sporadic, six SDHD, two SDHB PPGLs). The mRNA and protein expression levels of CD98hc and LATs were evaluated in samples with different genetic backgrounds and imaging phenotypes. The qRT-PCR and immunohistochemical analyses were performed in 14 and 16 tumor samples, respectively.

Results

The SDHx mutated samples exhibited a significant decrease in mRNA expression of LAT3 when compared to sporadic PPGLs (P?=?0.042). There was also a statistical trend toward decreased CD98hc (P?=?0.147) and LAT4 (P?=?0.012) levels in SDHx vs sporadic PPGLs. No difference was observed for LAT1/LAT2 mRNA levels. LAT1 protein was expressed in 15 out of 16 (93.75%) SDHx tumors, regardless of the ¹⁸F-FDOPA positivity. LAT1 and CD98hc were co-expressed in 6/8 ¹⁸F-FDOPA-negative PPGLs. In contrast, in one case with absence of LAT1/CD98hc, ¹⁸F-FDOPA uptake was positive and attributed to LAT4 expression.

Conclusions

We conclude that down-regulation of LAT1/CD98hc cannot explain the imaging phenotype of SDHx-related PPGLs. A reduced activity of LAT1 remains the primary hypothesis possibly due to a modification of intracellular amino acid content which may reduce ¹⁸F-FDOPA uptake.

     

Compared to <Superscript>123</Superscript>I-MIBG SPECT/CT, <Superscript>18</Superscript>F-DOPA PET/CT provides accurate tumor extent in patients with extra-adrenal paraganglioma

Aim

The aim of this study was to compare the accuracy of ¹²³I-MIBG SPECT/CT with that of ¹⁸F-DOPA PET/CT for staging extra-adrenal paragangliomas (PGLs) using both functional and anatomical images (i.e., combined cross-sectional imaging) as the reference standards.

Methods

Three men and seven women (age range 26–73 years) with anatomical and/or histologically proven disease were included in this study. Three patients had either metastatic head-and-neck paragangliomas (HNPGLs) or multifocal PGL, and seven patients had nonmetastatic disease. Comparative evaluation included morphological imaging with CT, functional imaging with ¹⁸F-DOPA PET, and ¹²³I-MIBG imaging including SPECT/CT. Imaging results were analyzed on a per-patient and per-lesion basis.

Results

On a per-patient basis, ¹⁸F-DOPA PET’s detection rate for both nonmetastatic and metastatic/multifocal disease was 100%, whereas that of planar ¹²³I-MIBG imaging alone was 10.0% and that of ¹²³I-MIBG SPECT/CT was 20.0%. Overall, on a per-lesion basis, ¹⁸F-DOPA PET showed a sensitivity of 69.2% (McNemar p?<?0.001) compared with anatomical imaging. Sensitivity of planar ¹²³I-MIBG scintigraphy was 5.6%, and that of SPECT/CT was 11.1% (McNemar p?<?0.0001). Overall, ¹⁸F-DOPA PET identified 18 lesions, and anatomical imaging identified 26 lesions; planar ¹²³IMIBG imaging identified only 1 lesion, and SPECT/CT, 2 lesions.

Conclusion

¹⁸F-DOPA PET is more sensitive than is ¹²³I-MIBG imaging, including SPECT/CT, for staging HNPGL. Combined functional and anatomical imaging (PET/CT) is indicated to exclude metastatic disease in extra-adrenal PGL.

     

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.

     

<Emphasis Type="Italic">IDH</Emphasis> mutation is paradoxically associated with higher <Superscript>18</Superscript>F-FDOPA PET uptake in diffuse grade II and grade III gliomas

Purpose

The World Health Organization Classification of Tumors of the Central Nervous System has recently been updated by the integration of diagnostic and prognostic molecular parameters, giving pivotal attention to IDH mutation as a favourable factor. Amino acid PET is increasingly used in the management of gliomas, but its prognostic value is a matter of debate. The aim of this study was to assess the relationship between IDH mutation and ¹⁸F-FDOPA uptake on PET in newly diagnosed gliomas.

Methods

A total of 43 patients, presenting with diffuse astrocytic and oligodendroglial grade II and III gliomas, reclassified according to the 2016 WHO classification of tumours of the CNS, were retrospectively included. They had all undergone ¹⁸F-FDOPA PET at an initial stage before surgery and histological diagnosis. ¹⁸F-FDOPA uptake values were compared between patients with and without IDH mutation in terms of maximum standardized uptake value (SUVmax) ratios between tumour and normal contralateral brain (T/N), and between tumour and striatum (T/S).

Results

Patients with IDH mutation showed higher ¹⁸F-FDOPA T/N SUVmax ratios (1.6 vs. 1.2) and T/S SUVmax ratios (0.9 vs. 0.6) than patients without IDH mutation (p?<?0.05).

Conclusion

This study showed paradoxically higher ¹⁸F-FDOPA uptake in diffuse grade II and III gliomas with IDH mutation. Despite evident interest in the management of gliomas, and especially in relation to posttherapy evaluation, our findings raise the question of the prognostic value of ¹⁸F-FDOPA uptake on PET uptake in this group of patients. This may be related to differences in amino acid integration, metabolism, or cell differentiation.

     

<Superscript>68</Superscript>Ga-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.

     

Prospective comparison of <Superscript>68</Superscript>Ga-PSMA PET/CT, <Superscript>18</Superscript>F-sodium fluoride PET/CT and diffusion weighted-MRI at for the detection of bone metastases in biochemically recurrent prostate cancer

Purpose

To prospectively compare diagnostic accuracies for detection of bone metastases by ⁶⁸Ga-PSMA PET/CT, ¹⁸F-NaF PET/CT and diffusion-weighted MRI (DW₆₀₀-MRI) in prostate cancer (PCa) patients with biochemical recurrence (BCR).

Methods

Sixty-eight PCa patients with BCR participated in this prospective study. The patients underwent ⁶⁸Ga-PSMA PET/CT, a ¹⁸F-NaF PET/CT and a DW₆₀₀-MRI (performed in accordance with European Society of Urogenital Radiology guidelines, with b values of 0 and 600 s/mm²). Bone lesions were categorized using a three-point scale (benign, malignant or equivocal for metastases) and a dichotomous scale (benign or metastatic) for each imaging modality by at least two experienced observers. A best valuable comparator was defined for each patient based on study-specific imaging, at least 12 months of clinical follow-up and any imaging prior to the study and during follow-up. Diagnostic performance was assessed using a sensitivity analysis where equivocal lesions were handled as non-metastatic and then as metastatic.

Results

Ten of the 68 patients were diagnosed with bone metastases. On a patient level, sensitivity, specificity and the area under the curve (AUC) by receiver operating characteristic analysis were, respectively, 0.80, 0.98–1.00 and 0.89–0.90 for ⁶⁸Ga-PSMA PET/CT (n?=?68 patients); 0.90, 0.90–0.98 and 0.90–0.94 for ¹⁸NaF PET/CT (n?=?67 patients); and 0.25–0.38, 0.87–0.92 and 0.59–0.62 for DW₆₀₀-MRI (n?=?60 patients). The diagnostic performance of DW₆₀₀-MRI was significantly lower than that of ⁶⁸Ga-PSMA PET/CT and ¹⁸NaF PET/CT for diagnosing bone metastases (p?<?0.01), and no significant difference in the AUC was seen between ⁶⁸Ga-PSMA PET/CT and ¹⁸NaF PET/CT (p?=?0.65).

Conclusion

⁶⁸Ga-PSMA PET/CT and ¹⁸F-NaF PET/CT showed comparable and high diagnostic accuracies for detecting bone metastases in PCa patients with BCR. Both methods performed significantly better than DW₆₀₀-MRI, which was inadequate for diagnosing bone metastases when conducted in accordance with European Society of Urogenital Radiology guidelines.

     

<Superscript>68</Superscript>Ga-PSMA PET/CT in the evaluation of bone metastases in prostate cancer

Purpose

The aims of this retrospective analysis were to compare ⁶⁸Ga-PSMA PET findings and low-dose CT findings (120 kV, 30 mA), and to obtain semiquantitative and quantitative ⁶⁸Ga-PSMA PET data in patients with prostate cancer (PC) bone metastases.

Methods

In total, 152 PET/CT scans from 140 patients were evaluated. Of these patients, 30 had previously untreated primary PC, and 110 had biochemical relapse after treatment of primary PC. All patients underwent dynamic PET/CT scanning of the pelvis and lower abdomen as well as whole-body PET/CT with ⁶⁸Ga-PSMA-11. The PET/CT scans were analysed qualitatively (visually), semiquantitatively (SUV), and quantitatively based on a two-tissue compartment model and a noncompartmental approach leading to the extraction of the fractal dimension. Differences were considered significant for p values <0.05.

Results

In total, 168 ⁶⁸Ga-PSMA-positive and 113 CT-positive skeletal lesions were detected in 37 patients (8 with primary PC, 29 with biochemical recurrence). Of these 168 lesions, 103 were both ⁶⁸Ga-PSMA PET-positive and CT-positive, 65 were only ⁶⁸Ga-PSMA-positive, and 10 were only CT-positive. The Yang test showed that there were significantly more ⁶⁸Ga-PSMA PET-positive lesions than CT-positive lesions. Association analysis showed that PSA plasma levels were significantly correlated with several ⁶⁸Ga-PSMA-11-associated parameters in bone metastases, including the degree of tracer uptake (SUV_average and SUV_max), its transport rate from plasma to the interstitial/intracellular compartment (K₁), its rate of binding to the PSMA receptor and its internalization (k₃), its influx rate (K_i), and its distribution heterogeneity.

Conclusion

⁶⁸Ga-PSMA PET/CT is a useful diagnostic tool in the detection of bone metastases in PC. ⁶⁸Ga-PSMA PET visualizes more bone metastases than low-dose CT. PSA plasma levels are significantly correlated with several ⁶⁸Ga-PSMA PET parameters.

     

The utility of PET/CT with <Superscript>68</Superscript>Ga-DOTATOC in sarcoidosis: comparison with <Superscript>67</Superscript>Ga-scintigraphy

Objective

This study was designed to compare the clinical efficacy of ⁶⁸Ga-DOTA-Tyr-octreotide (DOTATOC)-positron emission tomography (PET)/computed tomography (CT) with that of conventional ⁶⁷Ga-scintigraphy (GS), and to correlate quantitative parameters on DOTATOC-PET/CT with clinical data, in patients with sarcoidosis.

Methods

Twenty patients who were histologically and/or clinically diagnosed with sarcoidosis and underwent both DOTATOC-PET/CT and GS were analyzed in this study. The numbers of patients with positive findings for each organ were determined. The total numbers of involved nodal areas in the chest, as determined by DOTATOC-PET and gallium single-photon emission tomography (Ga-SPECT), were compared. The correlations between quantitative parameters on PET and clinical laboratory data were evaluated.

Results

DOTATOC-PET/CT was positive in 19 patients, being negative in only one patient with chronic inactive sarcoidosis, whereas GS was positive in 17 patients. DOTATOC-PET/CT visualized more lesions in lymph nodes, uvea, and muscles than did Ga-scintigraphy and identified more involved areas than did GS-SPECT (p < 0.0001). Whole-body active lesion volume showed a significant, but moderate correlation with angiotensin-converting enzyme level (ρ = 0.64, p = 0.0044).

Conclusions

PET/CT with DOTATOC may be superior to conventional GS in detecting sarcoidosis lesions, especially in lymph nodes, uvea, and muscles. Volumetric parameters in DOTATOC-PET/CT may be helpful in estimating the activity of sarcoidosis.

     

Comparison of hybrid <Superscript>68</Superscript>Ga-PSMA-PET/CT and <Superscript>99m</Superscript>Tc-DPD-SPECT/CT for the detection of bone metastases in prostate cancer patients: <Emphasis Type="Italic">Additional value of morphologic information from low dose CT</Emphasis>

Purpose

This study compared ⁶⁸Gallium-prostate-specific-membrane-antigen based Positron-emission-tomography (⁶⁸Ga-PSMA-PET) and ^99metastabletechnetium-3,3-diphospho-1,2-propanedicarbonacid (^99mTc-DPD-SPECT) in performing skeletal staging in prostate cancer (PC) patients and evaluated the additional value of the information from low-dose-computed tomography (CT).

Materials and Methods

In this retrospective study, 54 patients who received ⁶⁸Ga-PSMA-PET/CT and ^99mTc-DPD-SPECT/CT within 80 days were extracted from our database. Osseous lesions were classified as benign, malignant or equivocal. Lesion, region and patient based analysis was performed with and without CT fusion. The reference standard was generated by defining a best valuable comparator (BVC) containing information from all available data.

Results

In the patient based analysis, accuracies measured as “area-under-the-curve” (AUC) for ⁶⁸Ga-PSMA-PET, ^99mTc-SPECT, ⁶⁸Ga-PSMA-PET/CT and ^99mTc-SPECT/CT were 0.97-0.96, 0.86-0.83, 1.00 and 0.83, respectively (p<0.05) (ranges = optimistic vs. pessimistic view). Region based analysis resulted in the following sensitivities and specificities: 91.8-97.7%, 100-99.5% (PET); 61.2-70.6%, 99.8-98.3% (SPECT); 97.7%, 100% (PET/CT), 69.4% and 98.3% (SPECT/CT) (p<0.05). The amount of correct classifications of equivocal lesions by CT was significantly higher in PET (100%) compared to SPECT (52.4%) (p<0.05).

Conclusion

⁶⁸Ga-PSMA-PET outperforms ^99mTc-DPD-SPECT in detecting bone metastases in PC patients. Additional information from low-dose-CT resulted in a significant reduction in equivocal lesions in both modalities, however ⁶⁸Ga-PSMA-PET benefited most.

Key Points

? Ga-PSMA-PET outperforms ^99m Tc-DPD-SPECT in skeletal staging in prostate cancer patients ? Proportion of equivocal decisions was significantly reduced by CT-fusion in both modalities ? Ga-PSMA-PET benefits more from CT information, compared to ^99m Tc-DPD-SPECT

     

Diagnosis of recurrent prostate cancer with PET/CT imaging using the gastrin-releasing peptide receptor antagonist <Superscript>68</Superscript>Ga-RM2: Preliminary results in patients with negative or inconclusive [<Superscript>18</Superscript>F]Fluoroethylcholine-PET/CT

Purpose/background

[¹⁸F]fluoroethylcholine (¹⁸FECH) has been shown to be a valuable PET-tracer in recurrent prostate cancer (PCa), but still has limited accuracy. RM2 is a gastrin-releasing peptide receptor (GRPr) antagonist that binds to GRPr on PCa cells. Recent studies suggest that GRPr imaging with PET/CT is a promising technique for staging and restaging of PCa. We explore the value of GRPr-PET using the ⁶⁸Ga-labeled GRPr antagonist RM2 in a selected population of patients with biochemically recurrent PCa and a negative/inconclusive ¹⁸FECH-PET/CT.

Material and methods

In this retrospective study 16 men with biochemical PCa relapse and negative (n = 14) or inconclusive (n = 2) ¹⁸FECH-PET/CT underwent whole-body ⁶⁸Ga-RM2-PET/CT. Mean time from ¹⁸FECH-PET/CT to ⁶⁸Ga-RM2-PET/CT was 6.1 ± 6.8 months. Primary therapies in these patients were radical prostatectomy (n = 13; 81.3%) or radiotherapy (n = 3; 18.7%). 14/16 patients (87.5%) had already undergone salvage therapies because of biochemical relapse prior to ⁶⁸Ga-RM2-PET/CT imaging. Mean ± SD PSA at ⁶⁸Ga-RM2-PET/CT was 19.4 ± 53.5 ng/ml (range 1.06–226.4 ng/ml).

Results

⁶⁸Ga-RM2-PET/CT showed at least one region with focal pathological uptake in 10/16 patients (62.5%), being suggestive of local relapse (n = 4), lymph node metastases (LNM; n = 4), bone metastases (n = 1) and lung metastasis with hilar LNM (n = 1). Seven of ten positive ⁶⁸Ga-RM2 scans were positively confirmed by surgical resection and histology of the lesions (n = 2), by response to site-directed therapies (n = 2) or by further imaging (n = 3). Patients with a positive ⁶⁸Ga-RM2-scan showed a significantly higher median PSA (6.8 ng/ml, IQR 10.2 ng/ml) value than those with a negative scan (1.5 ng/ml, IQR 3.1 ng/ml; p = 0.016). Gleason scores or concomitant antihormonal therapy had no apparent impact on the detection of recurrent disease.

Conclusion

Even in this highly selected population of patients with known biochemical recurrence but negative or inconclusive ¹⁸FECH-PET/CT, a ⁶⁸Ga-RM2-PET/CT was helpful to localize PCa recurrence in the majority of the cases. Thus, ⁶⁸Ga-RM2-PET/CT deserves further investigation as a promising imaging modality for imaging PCa recurrence.

     

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.

     

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.

     

Prognostic implications of <Superscript>62</Superscript>Cu-diacetyl-bis (<Emphasis Type="Italic">N</Emphasis><Superscript>4</Superscript>-methylthiosemicarbazone) PET/CT in patients with glioma

Objective

The potential of positron emission tomography/computed tomography using ⁶²Cu-diacetyl-bis (N⁴-methylthiosemicarbazone) (⁶²Cu-ATSM PET/CT), which was originally developed as a hypoxic tracer, to predict therapeutic resistance and prognosis has been reported in various cancers. Our purpose was to investigate prognostic value of ⁶²Cu-ATSM PET/CT in patients with glioma, compared to PET/CT using 2-deoxy-2-[¹⁸F]fluoro-d-glucose (¹⁸F-FDG).

Method

56 patients with glioma of World Health Organization grade 2–4 were enrolled. All participants had undergone both ⁶²Cu-ATSM PET/CT and ¹⁸F-FDG PET/CT within mean 33.5 days prior to treatment. Maximum standardized uptake value and tumor/background ratio were calculated within areas of increased radiotracer uptake. The prognostic significance for progression-free survival and overall survival were assessed by log-rank test and Cox’s proportional hazards model.

Results

Disease progression and death were confirmed in 37 and 27 patients in follow-up periods, respectively. In univariate analysis, there was significant difference of both progression-free survival and overall survival in age, tumor grade, history of chemoradiotherapy, maximum standardized uptake value and tumor/background ratio calculated using ⁶²Cu-ATSM PET/CT. Multivariate analysis revealed that maximum standardized uptake value calculated using ⁶²Cu-ATSM PET/CT was an independent predictor of both progression-free survival and overall survival (p?<?0.05). In a subgroup analysis including patients of grade 4 glioma, only the maximum standardized uptake values calculated using ⁶²Cu-ATSM PET/CT showed significant difference of progression-free survival (p?<?0.05).

Conclusions

⁶²Cu-ATSM PET/CT is a more promising imaging method to predict prognosis of patients with glioma compared to ¹⁸F-FDG PET/CT.

     

Correlation of <Superscript>18</Superscript>F-FDG and <Superscript>11</Superscript>C-methionine uptake on PET/CT with Ki-67 immunohistochemistry in newly diagnosed intracranial meningiomas

Objective

We evaluated the uptake of 2-deoxy-2-¹⁸F-fluoro-d-glucose (FDG) and l-[methyl-¹¹C]-methionine (MET) in patients with newly diagnosed intracranial meningiomas and correlated the results with tumor proliferation.

Methods

Data from 22 patients with newly diagnosed intracranial meningioma (12 grade I and 10 grade II) who underwent both FDG and MET brain PET/CT studies were retrospectively analyzed. The PET images were evaluated by a qualitative method and semiquantitative analysis using standardized uptake value (SUV) (SUV_max and SUV_peak) and tumor-to-reference tissue ratio (T_max/N ratio and T_peak/N ratio). Proliferative activity as indicated by the Ki-67 index was estimated in tissue specimens.

Results

MET PET/CT showed a higher detection rate of meningioma than did FDG PET/CT (100 vs. 46%, respectively). The T_max/N ratio and T_peak/N ratio on MET PET/CT were significantly higher than those on FDG PET/CT (p?<?0.001 and p?<?0.001, respectively). There was a significant difference between grades I and II with respect to FDG SUVmax (p?=?0.003), FDG SUV_peak (p?=?0.003), FDG T_max/N ratio (p?=?0.02), FDG T_peak/N ratio (p?=?0.006), MET SUV_max (p?=?0.002), MET SUV_peak (p?=?0.002), MET T_max/N ratio (p?=?0.002), and MET T_peak/N ratio (p?=?0.002). There was a significant correlation between Ki-67 index and FDG PET/CT for SUV_max (p?=?0.02), SUV_peak (p?=?0.005), and T_peak/N ratio (p?=?0.05) and between Ki-67 index and MET PET/CT for SUV_max (p?=?0.004), SUV_peak (p?=?0.007), T_max/N ratio (p?=?0.002), and T_peak/N ratio (p?=?0.004).

Conclusion

MET PET/CT showed a high sensitivity compared with FDG PET/CT for detection of newly diagnosed WHO grades I and II intracranial meningiomas. Both FDG and MET uptake were found to be useful for evaluating tumor proliferation in meningiomas.

     

<Superscript>68</Superscript>Ga-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.

     

A revisit to quantitative PET with <Superscript>18</Superscript>F-FDOPA of high specific activity using a high-resolution condition in view of application to regenerative therapy

Objective

With the advent of regenerative/cell therapy for Parkinson’s disease (PD), ¹⁸F-FDOPA has drawn new attention as a biomarker of the therapeutic that cannot be evaluated with radiopharmaceuticals for dopamine transporter. Since most previous ¹⁸F-FDOPA PET studies were carried out many years ago with a PET scanner of lower resolution and with ¹⁸F-FDOPA of low specific activity synthesized from ¹⁸F-F₂, we used a newer PET/CT scanner with a high-resolution condition and ¹⁸F-FDOPA synthesized from ¹⁸F-F^? to re-evaluate this technique on normal subjects and patients with PD, together with D₂ receptor imaging with ¹¹C-raclopride (RAC).

Methods

PET scans were carried out with ¹⁸F-FDOPA for 120 min and with ¹¹C-RAC for 60 min on 10 patients clinically diagnosed with PD and on 10 normal control subjects. Image reconstruction parameters were optimized with phantom experiments. Graphical analysis and the ratio method for the late-phase images were performed to quantify the striatal uptakes.

Results

The specific activity of ¹⁸F-FDOPA was as high as 4000 MBq/nmol. We empirically determined appropriate reconstruction parameters to obtain high-resolution PET images with enough quantitative accuracy. Both ¹⁸F-FDOPA and ¹¹C-RAC PET showed higher uptake values on normal subjects than those of the previous studies probably due to high-resolution. Quantified ratio values strongly correlated with the graphical values for both tracers. Furthermore, ¹⁸F-FDOPA uptake in the substantia nigra was clearly visualized in most subjects.

Conclusion

Quantitative ¹⁸F-FDOPA and ¹¹C-RAC PET scans using a high-resolution condition are considered to provide essential information for regenerative dopaminergic therapy. Furthermore, the ratio analysis for the late-phase PET scans with ¹⁸F-FDOPA and ¹¹C-RAC enhances the clinical utility of these dopaminergic PET as imaging biomarkers of PD.