High-quality <Superscript>124</Superscript>I-labelled monoclonal antibodies for use as PET scouting agents prior to <Superscript>131</Superscript>I-radioimmunotherapy

Purpose Monoclonal antibodies (MAbs) labelled with ¹²⁴I are an attractive option for quantitative imaging with positron emission tomography (PET) in a scouting procedure prior to ¹³¹I-radioimmunotherapy (¹³¹I-RIT). In this study, three important items in the labelling of MAbs with ¹²⁴I were introduced to obtain optimal and reproducible product quality: restoration of radiation-induced inorganic deterioration of the starting ¹²⁴I solution, radiation protection during and after ¹²⁴I labelling, and synchronisation of the I/MAb molar ratio.Methods A new method was applied, using an NaIO₃/NaI carrier mix, realising in one step >90% restoration of deteriorated ¹²⁴I into the iodide form and chemical control over the I/MAb molar ratio. Chimeric MAb (cMAb) U36 and the murine MAbs 425 and E48 were labelled with ¹²⁴I using the so-called Iodogen-coated MAb method, as this method provides optimal quality conjugates under challenging radiation conditions. As a standardising condition, NaIO₃/NaI carrier mix was added at a stoichiometric I/MAb molar ratio of 0.9. For comparison, MAbs were labelled with ¹³¹I and with a mixture of ¹²⁴I, ¹²³I, ¹²⁶I and ¹³⁰I.Results Labelling with ¹²⁴I in this setting resulted in overall yields of >70%, a radiochemical purity of >95%, and preservation of MAb integrity and immunoreactivity, including at the patient dose level (85 MBq). No significant quality differences were observed when compared with ¹³¹I products, while the iodine isotope mixture gave exactly the same labelling efficiency for each of the isotopes, excluding a different chemical reactivity of ¹²⁴I-iodide. The scouting performance of ¹²⁴I-cMAb U36 labelled at the patient dose level was evaluated in biodistribution studies upon co-injection with ¹³¹I-labelled cMAb U36, and by PET imaging in nude mice bearing the head and neck cancer xenograft line HNX-OE. ¹²⁴I-cMAb and ¹³¹I-cMAb U36 labelled with a synchronised I/MAb molar ratio gave fully concordant tissue uptake values. Selective tumour uptake was confirmed with immuno-PET, revealing visualisation of 15 out of 15 tumours.Conclusion These results pave the way for renewed evaluation of the potential of ¹²⁴I-immuno-PET for clinical applications.     

<Superscript>18</Superscript>F-FDG PET/CT findings of sinonasal inverted papilloma with or without coexistent malignancy: comparison with MR imaging findings in eight patients

Introduction  Sinonasal inverted papilloma (IP) is known for high rate of associated malignancy. The purpose of this study was to identify ¹⁸F-FDG PET/CT findings of sinonasal IPs. We also tried to compare the PET/CT findings with the MR imaging findings. Methods  We retrospectively reviewed PET/CT and MR images of eight patients with sinonasal IP with (n = 6) or without (n = 2) coexistent squamous cell carcinoma (SCC). Particular attention was paid to correlate the PET/CT findings with the MR imaging findings in terms of area distribution of standard uptake values (SUVs) and a convoluted cerebriform pattern (CCP). Results  In two benign IPs, the maximum SUVs measured 8.2 and 7.8, respectively (mean, 8.0). In both tumors, MR images demonstrated a diffuse CCP. In six IPs with coexistent SCC, the maximum SUVs ranged from 13.3 to 31.9 (mean ± SD, 20.2 ± 6.6). In these tumors, MR images demonstrated a diffuse CCP in two, a partial CCP in three, and no CCP in one. A wide discrepancy was noted between MR imaging and PET/CT in terms of area distribution of a CCP and SUVs. Conclusion  In sinonasal lesions with MR imaging features of IP, ¹⁸F-FDG PET/CT demonstrating avid FDG uptake does not necessarily imply the presence of coexistent malignancy. In our small series, although IPs containing foci of SCC had consistently higher SUVs than IPs without SCC, the limited literature on this subject suggests that PET cannot be used reliably to make the distinction.     

Effect of the positron range of <Superscript>18</Superscript>F, <Superscript>68</Superscript>Ga and <Superscript>124</Superscript>I on PET/CT in lung-equivalent materials

Purpose  

The aim of this study was to investigate the effect of positron range on visualization and quantification in ¹⁸F, ⁶⁸Ga and ¹²⁴I positron emission tomography (PET)/CT of lung-like tissue.     

Quantitative assessment of atherosclerotic plaques on <Superscript>18</Superscript>F-FDG PET/MRI: comparison with a PET/CT hybrid system

Purpose

PET with ¹⁸F-FDG has the potential to assess vascular macrophage metabolism. ¹⁸F-FDG is most often used in combination with contrast-enhanced CT to localize increased metabolism to specific arterial lesions. Novel ¹⁸F-FDG PET/MRI hybrid imaging shows high potential for the combined evaluation of atherosclerotic plaques, due to the superior morphological conspicuity of plaque lesions. The purpose of this study was to evaluate the reliability and accuracy of ¹⁸F-FDG PET/MRI uptake quantification compared to PET/CT as a reference standard in patients with carotid atherosclerotic plaques.

Methods

The study group comprised 34 consecutive oncological patients with carotid plaques who underwent both PET/CT and PET/MRI with ¹⁸F-FDG on the same day. The presence of atherosclerotic plaques was confirmed by 3 T MRI scans. Maximum standardized uptake values (SUV_max) for carotid plaque lesions and the average SUV of the blood pool within the adjacent internal jugular vein were determined and target-to-blood ratios (TBRs, plaque to blood pool) were calculated.

Results

Atherosclerotic lesions with maximum colocalized focal FDG uptake were assessed in each patient. SUV_max values of carotid plaque lesions were significantly lower on PET/MRI than on PET/CT (2.3?±?0.6 vs. 3.1?±?0.6; P?<?0.01), but were significantly correlated between PET/CT and PET/MRI (Spearman’s r?=?0.67, P?<?0.01). In contrast, TBR_max values of plaque lesions were similar on PET/MRI and on PET/CT (2.2?±?0.3 vs. 2.2?±?0.3; P?=?0.4), and again were significantly correlated between PET/MRI and PET/CT (Spearman’s r?=?0.73, P?<?0.01). Considering the increasing trend in SUV_max and TBR_max values from early to delayed imaging time-points on PET/CT and PET/MRI, respectively, with continuous clearance of radioactivity from the blood, a slight underestimation of TBR_max values may also be expected with PET/MRI compared with PET/CT.

Conclusion

SUV_max and TBR_max values are widely accepted reference parameters for estimation of the radioactivity of atherosclerotic plaques on PET/CT. However, due to a systematic underestimation of SUV_max and TBR_max with PET/MRI, the optimal cut-off values indicating the presence of inflamed plaque tissue need to be newly defined for PET/MRI.

     

Diagnosis and dosimetry in differentiated thyroid carcinoma using <Superscript>124</Superscript>I PET: comparison of PET/MRI vs PET/CT of the neck

Purpose  

This study compares intrinsically coregistered ¹²⁴I positron emission tomography (PET) and CT (PET/CT) and software coregistered ¹²⁴I PET and MRI (PET/MRI) images for the diagnosis and dosimetry of thyroid remnant tissues and lymph node metastases in patients with differentiated thyroid carcinoma (DTC).     

Prospective comparison of combined <Superscript>18</Superscript>F-FDG and <Superscript>18</Superscript>F-NaF PET/CT vs. <Superscript>18</Superscript>F-FDG PET/CT imaging for detection of malignancy

Purpose  

Typically, ¹⁸F-FDG PET/CT and ¹⁸F-NaF PET/CT scans are done as two separate studies on different days to allow sufficient time for the radiopharmaceutical from the first study to decay. This is inconvenient for the patients and exposes them to two doses of radiation from the CT component of the examinations. In the current study, we compared the clinical usefulness of a combined ¹⁸F-FDG/¹⁸F-NaF PET/CT scan with that of a separate ¹⁸F-FDG-only PET/CT scan.     

<Superscript>13</Superscript>N-ammonia myocardial perfusion imaging with a PET/CT scanner: impact on clinical decision making and cost-effectiveness

Purpose The purpose of the study is to determine the impact of ¹³N-ammonia positron emission tomography (PET) myocardial perfusion imaging (MPI) on clinical decision making and its cost-effectiveness. Materials and methods One hundred consecutive patients (28 women, 72 men; mean age 60.9 ± 12.0 years; range 24–85 years) underwent ¹³N-ammonia PET scanning (and computed tomography, used only for attenuation correction) to assess myocardial perfusion in patients with known (n = 79) or suspected (n = 8) coronary artery disease (CAD), or for suspected small-vessel disease (SVD; n = 13). Before PET, the referring physician was asked to determine patient treatment if PET would not be available. Four weeks later, PET patient management was reassessed for each patient individually. Results Before PET management strategies would have been: diagnostic angiography (62 of 100 patients), diagnostic angiography and percutaneous coronary intervention (PCI; 6 of 100), coronary artery bypass grafting (CABG; 3 of 100), transplantation (1 of 100), or conservative medical treatment (28 of 100). After PET scanning, treatment strategies were altered in 78 patients leading to: diagnostic angiography (0 of 100), PCI (20 of 100), CABG (3 of 100), transplantation (1 of 100), or conservative medical treatment (76 of 100). Patient management followed the recommendations of PET findings in 97% of the cases. Cost-effectiveness analysis revealed lower costs of €206/patient as a result of PET scanning. Conclusion In a population with a high prevalence of known CAD, PET is cost-effective and has an important impact on patient management. P.T. Siegrist and L. Husmann contributed equally to this work.     

<Superscript>18</Superscript>F-labelled annexin V: a PET tracer for apoptosis imaging

Annexin V can be used to detect apoptotic cells in vitro and in vivo, based on its ability to identify extracellular phosphatidylserine, which arises during apoptosis. In the present study, we examined the synthesis of fluorine-18 labelled annexin V as a positron emission tomography tracer for apoptosis imaging. The distribution of [¹⁸F]annexin V and technetium-99m labelled annexin V, a well-characterised SPET tracer for apoptosis imaging, was compared. [¹⁸F]annexin V was synthesised using N-succinimidyl 4-[¹⁸F]fluorobenzoate as an ¹⁸F labelling reagent. Synthesised and purified [¹⁸F]annexin V was confirmed by SDS-PAGE. In an ex vivo imaging experiment, [¹⁸F]annexin V was intravenously injected into rats 24 h after the induction of myocardial ischaemia, and accumulation in the left ventricle was examined. [¹⁸F]annexin V accumulated in the infarct area of the left ventricle, where apoptotic cells were observed. In separate experiments, [¹⁸F]annexin V or [^99mTc]annexin V was intravenously injected into ischaemic or normal animals, and the distribution of the tracers was compared. In ischaemic animals, accumulation of [¹⁸F]annexin V and [^99mTc]annexin V in the infarct area was about threefold higher than in the non-infarct area. Furthermore, the ratio of accumulation in the normal heart to the blood radioactivity was not significantly different between the tracers. In normal animals, however, the uptake of [¹⁸F]annexin V in the liver, spleen and kidney was much lower than that of [^99mTc]annexin V. The low uptake of [¹⁸F]annexin V in these organs might represent an advantage over [^99mTc]annexin V.     

The incremental value of <Superscript>18</Superscript>F-FDG PET/CT in paediatric malignancies

PURPOSE: (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) imaging has been used in the assessment of paediatric malignancies. PET/CT increases the diagnostic accuracy in adult cancer patients. The present study assesses the incremental value of FDG PET/CT in paediatric malignancies. METHODS: A total of 118 (18)FDG PET/CT studies of 46 paediatric patients were reviewed retrospectively. PET and PET/CT results were classified as malignant, equivocal or benign, compared on a site- and study-based analysis, and also compared with the clinical outcome. RESULTS: Three hundred and twenty-four sites of increased FDG uptake were detected. Discordant PET and PET/CT interpretations were found in 97 sites (30%) in 27 studies (22%). PET yielded a statistically significant higher proportion of equivocal and a lower proportion of benign lesion and study results (p<0.001) than PET/CT. With PET there were 153 benign (47%), 84 (26%) equivocal and 87 (27%) malignant sites, while PET/CT detected 226 benign (70%), 10 (3%) equivocal and 88 (27%) malignant lesions. PET/CT mainly improved the characterisation of uptake in brown fat (39%), bowel (17%), muscle (8%) and thymus (7%). The study-based analysis showed that 17 equivocal and seven positive PET studies (20%) were interpreted as benign on PET/CT, while three equivocal studies were interpreted as malignant. The study-based sensitivity and specificity of PET/CT were 92% and 78% respectively. CONCLUSION: PET/CT significantly improved the characterisation of abnormal (18)FDG foci in children with cancer, mainly by excluding the presence of active malignancy in sites of increased tracer activity.     

Combined metabolic and morphologic imaging in thyroid carcinoma patients with elevated serum thyroglobulin and negative cervical ultrasonography: role of <Superscript>124</Superscript>I-PET/CT and FDG-PET

Purpose This study sought to compare iodine-124 positron emission tomography/computed tomography (¹²⁴I-PET/CT) and 2-[¹⁸F]fluoro-2-deoxy-d-glucose- (FDG-) PET in the detection of recurrent differentiated thyroid carcinoma (DTC) lesions in patients with increasing serum thyroglobulin (Tg), Tg-antibodies, or both, but without pathological cervical ultrasonography. We assessed the lesion detection accuracy of ¹²⁴I-PET alone, CT alone, ¹²⁴I-PET/CT, FDG-PET, and all these modalities combined. Material and methods The study included 21 patients (9 follicular, 12 papillary DTC) who had been rendered disease-free by thyroidectomy and radioiodine treatment (RIT) and followed up for 21–275 months after the last RIT. In all patients, FDG-PET was performed first. Within 1 week, ¹²⁴I-PET/CT was performed 24 h after oral administration of 43 ± 11 MBq ¹²⁴I. Imaging results were correlated with further clinical follow-up with (n = 12) or without (n = 9) post-study histology as the reference standard. Results The sensitivities for DTC lesion detection were: ¹²⁴I-PET, 49%; CT, 67%; ¹²⁴I-PET/CT, 80%; FDG-PET, 70%; and all modalities combined, 91%. For local recurrences (distant metastases), the sensitivities were: ¹²⁴I-PET, 60% (45%); CT, 20% (84%); and FDG-PET, 65% (71%). One-third of lesions demonstrated pathological tracer uptake with both ¹²⁴I- and FDG-PET, while two-thirds were positive with only one of these modalities. Conclusion Used together, ¹²⁴I-PET and CT allow localization of foci of highly specific ¹²⁴I uptake as well as non-iodine-avid lesions. The combination of ¹²⁴I-PET/CT and FDG-PET improves restaging in recurrent DTC by enabling detection on whole-body scans of local recurrence or metastases that are often not found if only one of the methods or other imaging modalities are applied.     

<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-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.

     

Bone and Calcified Soft Tissue Metastases of Medullary Thyroid Carcinoma Better Characterized on <Superscript>18</Superscript>F-Fluoride PET/CT than on <Superscript>68</Superscript>Ga-Dotatate PET/CT

Herein, we report a case of a 19-year-old man with multiple endocrine neoplasia type 2B (MEN2B) and medullary thyroid carcinoma (MTC) diagnosed when he was 12 years of age. The patient had previously undergone total thyroidectomy, cervical radiotherapy, and chemotherapy. He progressed with known bone, pulmonary, and lymph node metastases and was scanned with ¹⁸F-fluoride (¹⁸F-NaF) and ⁶⁸Ga-dotatate whole-body positron emission tomography/computed tomography (PET/CT) for metastatic disease monitoring. We found that the MTC bone metastases and soft tissue calcified metastases were better characterized on ¹⁸F-NaF PET/CT than on ⁶⁸Ga-dotatate PET/CT. This case illustrates that the ¹⁸F-NaF PET/CT could be helpful not only to the detection of bone metastases but also to the detection of calcified soft tissue metastases in patients with MTC.     

A study of plaque vascularization and inflammation using quantitative contrast-enhanced US and PET/CT

Background

Contrast-enhanced ultrasound (CEUS) is an in vivo methodology to quantify carotid plaque vascularization. Increased metabolism in plaques, measured as FDG uptake in PET/CT examination, has been associated with markers of inflammation in histological samples. In this study, we tested the association between FDG uptake and vascularization measured by CEUS to assess whether CEUS can be used as an in vivo marker of plaque vulnerability.

Methods

After informed consent, subjects aged >60 years with carotid plaque height exceeding 2.5 mm were recruited. CEUS was performed and analyzed using earlier described protocol and software, Contrast Quantification Program, which calculates the fraction of the plaque being contrast positive (CQP value). PET/CT examination was performed within 3 months of CEUS (median time 7 days). PET/CT images were acquired 90 min after FDG injection (2.7 MBq/kg). FDG uptake was measured as tissue background index (TBI), calculated using Spearman's rho as mean standard uptake value (SUV) of the plaque divided by mean SUV in the jugular vein (mean of 7 measuring points). Local ethics committee approved the study.

Results

We recruited 13 subjects (5 women) with a mean age of 71 years, 6 had a history of stroke or TIA, 1 had a history of ipsilateral stroke. CQP values showed a significant, positive correlation with TBI of carotid plaques, r = 0.67, p < 0.02.

Conclusions

Plaque vascularization measured by CEUS correlates positively with FDG uptake measured by PET/CT in humans. This indicates an association between vascularization and inflammation and/or hypoxia, supporting the use of CEUS as a non-invasive method to detect plaque vulnerability.     

<Superscript>18</Superscript>F-FDG PET/CT in paediatric lymphoma: comparison with conventional imaging

Purpose  

In children with Hodgkin’s disease and non-Hodgkin’s lymphoma, the ability of ¹⁸F-fluoro-2-deoxy-D-glucose PET/CT and conventional imaging (CI) to detect malignant lesions and predict poor lesion response to therapy was assessed and compared.