11C-Acetate as a new biomarker for PET/CT in patients with multiple myeloma: initial staging and postinduction response assessment

Purpose

We investigated the potential value of ¹¹C-acetate (ACT) PET/CT in characterizing multiple myeloma (MM) compared with ¹⁸F-FDG PET/CT. Bone marrow histological and whole-body (WB) MRI findings served as the reference standards.

Methods

In this prospective study, 15 untreated MM patients (10 men and 5 women, age range 48?69 years) underwent dual-tracer ¹¹C-ACT and ¹⁸F-FDG PET/CT and WB MRI for pretreatment staging, and 13 of them had repeated examinations after induction therapy. Diffuse and focal bone marrow uptake was assessed by visual and quantitative analyses, including measurement of the maximum standardized uptake value (SUV_max). Between-group differences and correlations were assessed with the Mann-Whitney U test and the Pearson test.

Results

At staging, all 15 patients had diffuse myeloma involvement upon bone marrow examination with 30–90 % of plasma cell infiltrates. Diffuse infiltration was detected in all of them (100 %) using ¹¹C-ACT with a positive correlation between bone marrow uptake values and percentages of plasma cell infiltrates (r = +0.63, p?=?0.01). In contrast, a diagnosis of diffuse infiltration could be established using ¹⁸F-FDG in only six patients (40 %). Focal lesions were shown in 13 patients on both ¹¹C-ACT PET/CT and WB MRI, and in 10 patients on ¹⁸F-FDG PET/CT. Focal lesions demonstrated ¹¹C-ACT uptake with a mean SUV_max of 11.4 ± 3.3 (range 4.6?19.6, n?=?59), which was significantly higher than the ¹⁸F-FDG uptake (mean SUV_max 6.6 ± 3.1, range 2.3?13.7, n?=?29; p?<?0.0001). After treatment, the diffuse bone marrow ¹¹C-ACT uptake showed a mean SUV_max reduction of 66 % in patients with at least a very good partial response versus 34 % in those with at most a partial response only (p?=?0.01).

Conclusion

PET/CT using ¹¹C-ACT as a biomarker showed a higher detection rate for both diffuse and focal myeloma lesions at diagnosis than using ¹⁸F-FDG, and may be valuable for response assessment.     

Role of 18F-FDG PET/CT in the prediction of gastric cancer recurrence after curative surgical resection

Purpose

The study evaluated the role of preoperative ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in the prediction of recurrent gastric cancer after curative surgical resection.

Methods

A total of 271 patients with gastric cancer who underwent ¹⁸F-FDG PET/CT and subsequent curative surgical resection were enrolled. All patients underwent follow-up for cancer recurrence with a mean duration of 24?±?12?months. ¹⁸F-FDG PET/CT images were visually assessed and, in patients with positive ¹⁸F-FDG cancer uptake, the maximum standardized uptake value (SUV_max) of cancer lesions was measured. ¹⁸F-FDG PET/CT findings were tested as prognostic factors for cancer recurrence and compared with conventional prognostic factors. Furthermore, ¹⁸F-FDG PET/CT findings were assessed as prognostic factors according to histopathological subtypes.

Results

Of 271 patients, 47 (17?%) had a recurrent event. Positive ¹⁸F-FDG cancer uptake was shown in 149 patients (55?%). Tumour size, depth of invasion, presence of lymph node metastasis, positive ¹⁸F-FDG uptake and SUV_max were significantly associated with tumour recurrence in univariate analysis, while only depth of invasion, positive ¹⁸F-FDG uptake and SUV_max had significance in multivariate analysis. The 24-month recurrence-free survival rate was significantly higher in patients with negative ¹⁸F-FDG uptake (95?%) than in those with positive ¹⁸F-FDG uptake (74?%; p?18F-FDG uptake was a significant prognostic factor in patients with tubular adenocarcinoma (p?=?0.003) or poorly differentiated adenocarcinoma (p?=?0.0001). However, only marginal significance was shown in patients with signet-ring cell carcinoma and mucinous carcinoma (p?=?0.05).

Conclusion

¹⁸F-FDG uptake of gastric cancer is an independent and significant prognostic factor for tumour recurrence. ¹⁸F-FDG PET/CT could provide effective information on the prognosis after surgical resection of gastric cancer, especially in tubular adenocarcinoma and poorly differentiated adenocarcinoma.     

18F-FAMT in patients with multiple myeloma: clinical utility compared to 18F-FDG

Objective

l-[3-¹⁸F]-alpha-methyltyrosine (¹⁸F-FAMT) is an amino-acid tracer for positron emission tomography (PET), with uptake related to overexpression of L-type amino-acid transporter 1 and proliferative activity in tumour cells. This study evaluated the diagnostic performance of ¹⁸F-FAMT PET compared with 2-[¹⁸F]-fluoro-2-deoxy-d-glucose (¹⁸F-FDG) PET in patients with multiple myeloma (MM).

Methods

Eleven patients with MM (newly diagnosed, n?=?3; relapsed after treatment, n?=?8) underwent whole-body ¹⁸F-FAMT and ¹⁸F-FDG PET within a 2-week interval. Magnetic resonance imaging (MRI) of the spine was also performed to assess patterns of bone marrow infiltration. Tracer uptake was semi-quantitatively evaluated using maximal standardized uptake value (SUV_max). Mean SUV was also determined for normal bone marrow and the aortic arch as mediastinal background SUV to calculate lesion-to-bone marrow (L/B) and lesion-to-mediastinum (L/M) ratios, respectively. Those values were statistically compared using Student??s t test.

Results

In 8 patients showing focal infiltration on MRI, 34 FDG-avid bone lesions were identified, with each showing increased FAMT uptake. Mean SUV_max and L/B ratio of FDG (3.1?±?1.2 and 3.3?±?1.9, respectively) were significantly higher than those of FAMT (2.0?±?1.0 and 2.6?±?1.1, respectively; p?<?0.05 each). In contrast, the L/M ratio of FDG showed no significant difference to that of FAMT (2.2?±?1.0 and 2.4?±?1.2, respectively; p?=?0.3).

Conclusions

Clear ¹⁸F-FAMT PET uptake was seen in most ¹⁸F-FDG-avid lesions among patients with MM, and an equivalent semi-quantitative value was obtained using L/M ratio. Our preliminary data suggest that ¹⁸F-FAMT PET provides a useful imaging modality for detecting active myelomatous lesions.     

Combined use of 18F-FDG PET/CT and MRI for response monitoring of breast cancer during neoadjuvant chemotherapy

Purpose

To explore the potential complementary value of PET/CT and dynamic contrast-enhanced MRI in predicting pathological response to neoadjuvant chemotherapy (NAC) of breast cancer and the dependency on breast cancer subtype.

Methods

We performed ¹⁸F-FDG PET/CT and MRI examinations before and during NAC. The imaging features evaluated on both examinations included baseline and changes in ¹⁸F-FDG maximum standardized uptake value (SUVmax) on PET/CT, and tumour morphology and contrast uptake kinetics on MRI. The outcome measure was a (near) pathological complete response ((near-)pCR) after surgery. Receiver operating characteristic curves with area under the curve (AUC) were used to evaluate the relationships between patient, tumour and imaging characteristics and tumour responses.

Results

Of 93 patients, 43 achieved a (near-)pCR. The responses varied among the different breast cancer subtypes. On univariate analysis the following variables were significantly associated with (near-)pCR: age (p?=?0.033), breast cancer subtype (p?<?0.001), relative change in SUVmax on PET/CT (p?<?0.001) and relative change in largest tumour diameter on MRI (p?<?0.001). The AUC for the relative reduction in SUVmax on PET/CT was 0.78 (95 % CI 0.68–0.88), and for the relative reduction in tumour diameter at late enhancement on MRI was 0.79 (95 % CI 0.70–0.89). The AUC increased to 0.90 (95 % CI 0.83–0.96) in the final multivariate model with PET/CT, MRI and breast cancer subtype combined (p?=?0.012).

Conclusion

PET/CT and MRI showed comparable value for monitoring response during NAC. Combined use of PET/CT and MRI had complementary potential. Research with more patients is required to further elucidate the dependency on breast cancer subtype.     

18F-FDG uptake by spleen helps rapidly predict the dose level after total body irradiation in a Tibetan minipig model

Objectives

To investigate whether ¹⁸F- FDG uptake can be applied in dosimetry to facilitate the rapid and accurate evaluation of individual radiation doses after a nuclear accident.

Methods

Forty-eight Tibetan minipigs were randomised into a control group (n?=?3) and treatment groups (n?=?45). ¹⁸F-FDG combined positron-emission tomography and computed tomography (PET/CT) were carried out before total body irradiation (TBI) and at 6, 24 and 72?h after receiving TBI doses ranging from 1 to 11?Gy. Spleen tissues and blood samples were also collected for histological examination, apoptosis and blood analysis.

Results

Mean standardised uptake values (SUVs) of the spleen showed significant differences between the experimental and the control groups. Spleen SUV at 6?h post-irradiation showed significant correlation with radiation dose; Spearman’s correlation coefficient was 0.97 (P?Conclusions In the Tibetan minipig model, radiation doses have a close relationship with the ¹⁸F-FDG uptake of the spleen. This finding suggests that ¹⁸F-FDG PET/CT may be useful for the rapid detection of individual radiation doses.

Key Points

? The spleen responds rapidly and is very sensitive to total body irradiation. ? In Tibetan minipigs, the radiation dose is closely related to the 18F-FDG uptake of the spleen. ? 18F-FDG PET/CT may be useful for the prediction of individual radiation doses.     

Diffusion-weighted MRI, 11C-choline PET and 18F-fluorodeoxyglucose PET for predicting the Gleason score in prostate carcinoma

Objectives

To evaluate the accuracy of transrectal ultrasound-guided (TRUS) biopsy, diffusion-weighted (DW) magnetic resonance imaging (MRI), ¹¹C-choline (CHOL) positron emission tomography (PET), and ¹⁸F-fluorodeoxyglucose (FDG) PET in predicting the prostatectomy Gleason risk (GR).

Methods

The study included 21 patients who underwent TRUS biopsy and multi-technique imaging before radical prostatectomy. Values from five different tests (TRUS biopsy, DW MRI, CHOL PET, FDG PET, and combined DW MRI/CHOL PET) were correlated with the prostatectomy GR using Spearman’s ρ. Tests that were found to have significant correlations were used to classify patients into GR groups.

Results

The following tests had significant correlations with prostatectomy GR: TRUS biopsy (ρ?=?0.617, P?=?0.003), DW MRI (ρ?=?–0.601, P?=?0.004), and combined DW MRI/CHOL PET (ρ?=?–0.623, P?=?0.003). CHOL PET alone and FDG PET only had weak correlations. The correct GR classification rates were 67 % with TRUS biopsy, 67 % with DW MRI, and 76 % with combined DW MRI/CHOL PET.

Conclusions

DW MRI and combined DW MRI/CHOL PET have significant correlations and high rates of correct classification of the prostatectomy GR, the strength and accuracy of which are comparable with TRUS biopsy.

Key Points

? Accurate determination of the Gleason score is essential for prostate cancer management. ? DW MRI ± CHOL PET correlated significantly with prostatectomy Gleason score. ? These correlations are similar to that between TRUS biopsy and prostatectomy.     

PET/CT studies of multiple myeloma using 18 F-FDG and 18 F-NaF: comparison of distribution patterns and tracers’ pharmacokinetics

Objective

The aim of this prospective study is to evaluate the combined use of fluorine-18 fluorodeoxyglucose (¹⁸?F-FDG) and fluorine-18 sodium fluoride (¹⁸?F-NaF) PET/CT in the skeletal assessment of patients with multiple myeloma (MM) and to compare the efficacy of these two PET tracers regarding detection of myeloma-indicative osseous lesions.

Patients and methods

The study includes 60 patients with multiple myeloma (MM) diagnosed according to standard criteria. All patients underwent dynamic (dPET/CT) scanning of the pelvis as well as whole body PET/CT studies with both tracers. The interval between the two exams was one day. Sites of focal increased ¹⁸?F-FDG uptake were considered as highly suspicious of myelomatous involvement. The lesions detected on the ¹⁸?F-NaF PET/CT scans were then correlated with those detected on ¹⁸?F-FDG PET/CT, which served as a reference. Moreover, the ¹⁸?F-FDG PET/CT results were also correlated with the low-dose CT findings. The evaluation of dPET/CT studies was based on qualitative evaluation, SUV calculation, and quantitative analysis based on a 2-tissue compartment model and a non-compartmental approach.

Results

Whole body ¹⁸?F-FDG PET/CT revealed approximately 343 focal lesions while ¹⁸?F-NaF PET/CT revealed 135 MM-indicative lesions (39 % correlation). CT demonstrated 150 lesions that correlated with those in ¹⁸?F-FDG PET/CT (44 % correlation). Six patients demonstrated a diffuse pattern of disease with ¹⁸?F-FDG, while 15 of them had a mixed (diffuse and focal) pattern of skeletal ¹⁸?F-FDG uptake. A high number of degenerative, traumatic and arthritic disease lesions were detected with ¹⁸?F-NaF PET/CT. In three patients with multiple focal ¹⁸?F-FDG-uptake, ¹⁸?F-NaF PET/CT failed to demonstrate any bone lesion. The dPET/CT scanning of the pelvic area with ¹⁸?F-FDG and ¹⁸?F-NaF revealed 77 and 24 MM-indicative lesions, respectively. Kinetic analysis of ¹⁸?F-FDG revealed the following mean values: SUV_aver?=?5.1, k₁?=?0.37 (1/min), k₃?=?0.10 (1/min), V_B?=?0.06, influx?=?0.04 (1/min), FD?=?1.28; the respective values for ¹⁸?F-NaF were SUV_average?=?10.7, k₁?=?0.25 (1/min), k₃?=?0.34 (1/min), V_B?=?0.02, influx?=?0.10 (1/min), FD?=?1.37. Apart from the correlation between V_B of ¹⁸?F-FDG and k₁ of ¹⁸?F-NaF (r?=?0.54), no other significant correlation was observed between the two tracers’ kinetic parameters. We found a significant correlation between FD and SUV_average (r?=?0.93), FD and SUV_max (r?=?0.80), FD and influx ( r?=?0.85), as well as between influx and SUV_average (r?=?0.74) for ¹⁸?F-FDG. In ¹⁸?F-NaF we observed the most significant correlations between FD and SUV_average (r?=?0.97), FD and SUV_max (r?=?0.87), and between influx and k₁ (r?=?0.72).

Conclusion

The combined use of ¹⁸?F-FDG PET/CT and ¹⁸?F-NaF PET/CT provides different molecular information regarding the biological processes that take place in a MM osseous lesion. ¹⁸?F-FDG PET/CT proved to be a more specific biomarker than ¹⁸?F-NaF PET/CT in multiple myeloma skeletal assessment.     

Prognostic value of pretreatment 18F-FDG PET/CT and human papillomavirus type 16 testing in locally advanced oropharyngeal squamous cell carcinoma

Purpose

Human papillomavirus type 16 (HPV-16) positivity is associated with favourable survival in oropharyngeal squamous cell carcinoma (OPSCC). We report here a study of the prognostic significance of ¹⁸F-FDG PET/CT functional parameters and HPV-16 infection in OPSCC patients.

Methods

We retrospectively analysed 60 patients with stage III or IV OPSCC who had had a pretherapy ¹⁸F-FDG PET/CT scan and had completed concurrent chemoradiotherapy (n?=?58) or curative radiotherapy (n?=?2). All patients were followed up for ≥24?months or until death. We determined total lesion glycolysis (TLG) and the maximal standardized uptake values (SUV_max) of the primary tumour and neck lymph nodes from the pretherapy ¹⁸F-FDG PET/CT scan. Optimal cut-offs of the ¹⁸F-FDG PET/CT parameters were obtained by receiver operating characteristic (ROC) curve analyses. Pretherapy tumour biopsies were studied by polymerase chain reaction to determine HPV infection status.

Results

The pretherapy tumour biopsies were positive for HPV-16 in 12 patients (20.0?%). Cox regression analyses revealed HPV-16 positivity and tumour TLG >135.3?g to be independently associated with overall survival (p?=?0.027 and 0.011, respectively). However, only tumour TLG >135.3?g was independently associated with progression-free survival, disease-free survival and locoregional control (p?=?0.011, 0.001 and 0.034, respectively). A scoring system was formulated to define distinct overall survival groups using tumour TLG and HPV-16 status. Patients positive for HPV-16 and with tumour TLG ≤135.3?g experienced better survival than those with tumour TLG >135.3?g and no HPV infection (p?=?0.001).

Conclusion

Tumour TLG was an independent predictor of survival in patients with locally advanced OPSCC. A scoring system was developed and may serve as a risk stratification strategy for guiding therapy.     

18F-FDOPA PET/CT for detection of recurrence in patients with glioma: prospective comparison with 18F-FDG PET/CT

Purpose

Differentiation between recurrence and radiation necrosis in patients with glioma is crucial, since the two entities have completely different management and prognosis. The purpose of the present study was to compare the efficacies of ¹⁸F-FDG PET/CT and 3,4-dihydroxy-6-[¹⁸F]fluoro-phenylalanine (¹⁸F-FDOPA) PET/CT in detection of recurrent gliomas.

Methods

A total of 28 patients (age 38.82?±?1.25 years; 85.7 % men) with histopathologically proven glioma with clinical/imaging suspicion of recurrence were evaluated using ¹⁸F-FDG PET/CT and ¹⁸F-FDOPA PET/CT. ¹⁸F-FDG PET/CT and ¹⁸F-FDOPA PET/CT images were evaluated qualitatively and semiquantitatively. The combination of clinical follow-up, repeat imaging and/or biopsy (when available) was taken as the reference standard.

Results

Based on the reference standard, 21 patients were positive and 7 were negative for tumour recurrence. The sensitivity, specificity and accuracy of ¹⁸F-FDG PET/CT were 47.6 %, 100 % and 60.7 %, respectively, and those of ¹⁸F-FDOPA PET/CT were 100 %, 85.7 % and 96.4 %, respectively. The results of ¹⁸F-FDG PET/CT and ¹⁸F-FDOPA PET/CT were concordant in 57.1 % of patients (16 of 28) and discordant in 42.9 % (12 of 28). The difference in the findings between ¹⁸F-FDG PET/CT and ¹⁸F-FDOPA PET/CT was significant (P?=?0.0005, McNemar’s test). The difference was significant for low-grade tumours (P?=?0.0039) but not for high-grade tumours (P?=?0.250).

Conclusion

¹⁸F-FDOPA PET/CT is highly sensitive and specific for detection of recurrence in glioma patients. It is superior to ¹⁸F-FDG PET/CT for this purpose and is especially advantageous in patients with low-grade gliomas.     

The impact of 18F-FDG PET on the management of patients with suspected large vessel vasculitis

Purpose

We aimed to assess the impact of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the management of patients with suspected large vessel vasculitis.

Methods

An international expert panel determined diagnoses and clinical management in patients with suspected large vessel vasculitis, with and without the results of ¹⁸F-FDG PET, respectively. The accuracy of the clinical diagnosis and the resulting clinical management with and without the ¹⁸F-FDG PET results were compared using logistic regression models.

Results

The analysis included 30 patients referred to a tertiary care centre with large vessel vasculitis and 31 controls. ¹⁸F-FDG PET had an overall sensitivity of 73.3% [95% confidence interval (CI) 54.1?C87.7%], a specificity of 83.9% (95% CI 66.3?C94.5%), a positive predictive value of 81.5% (95% CI 61.9?C93.7%) and a negative predictive value of 76.5% (95% CI 58.8?C89.3%). The diagnostic accuracy of ¹⁸F-FDG PET was higher in patients not receiving immunosuppressive drugs (93.3 vs 64.5%, p?=?0.006). Taken in context with other available diagnostic modalities, the addition of ¹⁸F-FDG PET increased the clinical diagnostic accuracy from 54.1 to 70.5% (p?=?0.04). The addition of ¹⁸F-FDG PET increased the number of indicated biopsies from 22 of 61 patients (36.1%) to 25 of 61 patients (41.0%) and changed the treatment recommendation in 8 of 30 patients (26.7%) not receiving immunosuppressive medication and in 7 of 31 patients (22.6%) receiving immunosuppressive medication.

Conclusion

¹⁸F-FDG PET is a sensitive and specific imaging tool for large vessel vasculitis, especially when performed in patients not receiving immunosuppressive drugs. It increases the overall diagnostic accuracy and has an impact on the clinical management in a significant proportion of patients.     

18F-FDG PET and intravascular ultrasonography (IVUS) images compared with histology of atherosclerotic plaques: 18F-FDG accumulates in foamy macrophages

Purpose

Intravascular ultrasonography (IVUS) and ¹⁸F-FDG PET have been used to evaluate the efficacy of antiatherosclerosis drugs. These two modalities image different characteristics of atherosclerotic plaques, and a comparison of IVUS and PET images with histology has not been performed. The aim of this study was to align IVUS and PET images using anatomic landmarks in Watanabe heritable hyperlipidaemic (WHHL) rabbits, enabling comparison of their depiction of aortic atherosclerosis. Cellular ¹⁸F-FDG localization was evaluated by ³H-FDG microautoradiography (micro-ARG).

Methods

A total of 19 WHHL rabbits (7 months of age) were divided into three groups: baseline (n?=?6), 3 months (n?=?4), and 6 months (n?=?9). PET, IVUS and histological images of the same aortic segments were analysed. Infiltration by foamy macrophages was scored from 0 to IV using haematoxylin and eosin (H&E) and antimacrophage immunohistochemical staining, and compared with ³H-FDG micro-ARG findings in two additional WHHL rabbits.

Results

IVUS images did not identify foamy macrophage deposition but revealed the area of intimal lesions (r?=?0.87). ¹⁸F-FDG PET revealed foamy macrophage distribution in the plaques. The intensity of ¹⁸F-FDG uptake was correlated positively with the degree of foamy macrophage infiltration. Micro-ARG showed identical ³H-FDG accumulation in the foamy macrophages surrounding the lipid core of the plaques.

Conclusion

F-FDG PET localized and quantified the degree of infiltration of foamy macrophages in atherosclerotic lesions. IVUS defined the size of lesions. ¹⁸F-FDG PET is a promising imaging technique for evaluating atherosclerosis and for monitoring changes in the composition of atherosclerotic plaques affecting their stability.     

Clinical significance of 18F-α-methyl tyrosine PET/CT for the detection of bone marrow invasion in patients with oral squamous cell carcinoma: comparison with 18F-FDG PET/CT and MRI

Objective

L-3-[¹⁸F]-fluoro-α-methyl tyrosine (¹⁸F-FAMT) is an amino acid tracer for positron emission tomography/computed tomography (PET/CT) which specifically transported into cancer cells by L-type amino acid transporter 1 (LAT1). LAT1 overexpression in tumors is significantly correlated with cell proliferation and angiogenesis. ¹⁸F-FAMT PET/CT, fluorine-18-fluorodeoxyglucose (¹⁸F-FDG) PET/CT and magnetic resonance imaging (MRI) were compared for their diagnostic performance in the detection of bone marrow invasion in patients with oral squamous cell carcinoma (OSCC).

Methods

Twenty-seven patients with OSCC on the upper or lower alveolar ridge underwent staging by MRI, ¹⁸F-FDG PET/CT and ¹⁸F-FAMT PET/CT studies before surgery. Post-surgical pathologic examination was used as the standard to determine the final diagnoses. The possibility of bone marrow invasion on MRI, ¹⁸F-FDG PET/CT and ¹⁸F-FAMT PET/CT were usually graded retrospectively into five-point score. Sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated according to the obtained scores.

Results

As the sensitivity of ¹⁸F-FDG PET/CT was highest (100 %) among that of MRI (95 %) and ¹⁸F-FAMT PET/CT (90 %), the specificity of ¹⁸F-FAMT PET/CT was highest (85.7 %) among that of MRI (57 %) and ¹⁸F-FDG PET/CT (14.3 %). The size of pathological tumor was accorded with that detected by ¹⁸F-FAMT PET/CT and was smaller than that detected by ¹⁸F-FDG PET/CT (P < 0.01). Significant difference was not found between ¹⁸F-FAMT PET tumor volume and pathological tumor volume.

Conclusions

¹⁸F-FAMT PET/CT was useful and more specific than MRI or ¹⁸F-FDG PET/CT in the detection of bone marrow invasion of OSCC and may contribute to minimize the extent of resection in oral surgery patient.     

Diagnostic accuracy of 18F-FDG PET/CT for detection of suspected recurrence in patients with oesophageal carcinoma

Purpose

To evaluate the role of ¹⁸F-FDG PET/CT in the detection of recurrence in patients with oesophageal carcinoma, suspected clinically or following conventional investigations.

Methods

This was a retrospective study. Data from 180 patients (age 56.3?±?10.4 years; 126 men, 54 women) with histopathologically proven oesophageal carcinoma (squamous cell 115, adenocarcinoma 59, neuroendocrine carcinoma 4, small cell 1, poorly differentiated 1) who had undergone 227 ¹⁸F-FDG PET/CT studies for suspected recurrence were analysed. Recurrence was suspected clinically or following conventional investigations. PET/CT images were revaluated by two nuclear medicine physicians in consensus. Findings were grouped into local, nodal and distant recurrence. Results were compared to those from contrast-enhanced (CE) CT when available (109 patients). Clinical/imaging follow-up (minimum 6 months) with histopathology (when available) was taken as the reference standard.

Results

Of the 227 ¹⁸F-FDG PET/CT studies,166 were positive and 61 were negative for recurrent disease. PET/CT showed local recurrence in 134, nodal recurrence in 115 and distant recurrence in 47, with more than one site of recurrence in 34. The PET/CT findings were true-positive in 153 studies, true-negative in 54, false-positive in 13 and false-negative in 7. The sensitivity of ¹⁸F-FDG PET/CT was 96 %, the specificity was 81 %, the positive and negative predictive values were 92 % and 89 %, respectively, and the accuracy was 91 %. PET/CT showed similar accuracy in patients with squamous cell carcinoma and in those with adenocarcinoma (P?=?0.181).¹⁸F-FDG PET/CT was more specific than CECT (67 % vs. 21 %; P?<?0.0001). PET/CT was superior to CECT for the detection of nodal recurrence (P?<?0.0001), but not local recurrence (P?=?0.093) or distant metastases (P?=?0.441).

Conclusion

¹⁸F-FDG PET/CT shows high accuracy in the detection of suspected recurrence in patients with oesophageal carcinoma. It is more specific than and is superior to CECT in the detection of nodal recurrence.     

Induction and repair of DNA double-strand breaks in blood lymphocytes of patients undergoing 18F-FDG PET/CT examinations

Purpose

The purpose of this study was to evaluate DNA double-strand breaks (DSBs) in blood lymphocytes of patients undergoing positron emission tomography (PET)/CT using γ-H2AX immunofluorescence microscopy and to differentiate between ¹⁸F-fluorodeoxyglucose (FDG) and CT-induced DNA lesions.

Methods

This study was approved by the local Ethics Committee and complies with Health Insurance Portability and Accountability Act (HIPAA) requirements. After written informed consent was obtained, 33 patients underwent whole-body ¹⁸F-FDG PET/CT (3?MBq/kg body weight, 170/100 reference mAs at 120?kV). The FDG PET and CT portions were performed as an initial CT immediately followed by the PET. Blood samples were obtained before, at various time points following ¹⁸F-FDG application and up to 24?h after the CT scan. Distinct foci representing DSBs were quantified in isolated lymphocytes using fluorescence microscopy after staining against the phosphorylated histone variant γ-H2AX.

Results

The DSB values at the various time points were significantly different (p?<?0.001). The median baseline level was 0.08/cell (range 0.06–0.12/cell). Peaks of radiation-induced DSBs were found 30?min after ¹⁸F-FDG administration (median excess foci 0.11/cell, range 0.06–0.27/cell) and 5?min after CT (median excess foci 0.17/cell, range 0.05–0.54/cell). A significant correlation between CT-induced DSBs and dose length product was obtained (ρ?=?0.898, p?<?0.001). After 24?h DSB values were still slightly but significantly elevated (median foci 0.11/cell, range 0.10–0.14/cell, p?=?0.003) compared to pre-exposure levels.

Conclusion

PET/CT-induced DSBs can be monitored using γ-H2AX immunofluorescence microscopy. Peak values may be obtained 30?min after ¹⁸F-FDG injection and 5?min after CT. The radionuclide contributes considerably to the total DSB induction in this setting.     

18F-FDG PET predicts survival after pretargeted radioimmunotherapy in patients with progressive metastatic medullary thyroid carcinoma

Purpose

PET is a powerful tool for assessing targeted therapy. Since ¹⁸F-FDG shows a potential prognostic value in medullary thyroid carcinoma (MTC), this study evaluated ¹⁸F-FDG PET alone and combined with morphological and biomarker evaluations as a surrogate marker of overall survival (OS) in patients with progressive metastatic MTC treated with pretargeted anti-CEA radioimmunotherapy (pRAIT) in a phase II clinical trial.

Methods

Patients underwent PET associated with morphological imaging (CT and MRI) and biomarker evaluations, before and 3 and 6 months, and then every 6 months, after pRAIT for 36 months. A combined evaluation was performed using anatomic, metabolic and biomarker methods. The prognostic value of the PET response was compared with demographic parameters at inclusion including age, sex, RET mutation, time from initial diagnosis, calcitonin and CEA concentrations and doubling times (DT), SUV_max, location of disease and bone marrow involvement, and with response using RECIST, biomarker concentration variation, impact on DT, and combined methods.

Results

Enrolled in the study were 25 men and 17 women with disease progression. The median OS from pRAIT was 3.7 years (0.2 to 6.5 years) and from MTC diagnosis 10.9 years (1.7 to 31.5 years). After pRAIT, PET/CT showed 1 patient with a complete response, 4 with a partial response and 24 with disease stabilization. The combined evaluation showed 20 responses. For OS from pRAIT, univariate analysis showed the prognostic value of biomarker DT (P?=?0.011) and SUV_max (P?=?0.038) calculated before pRAIT and impact on DT (P?=?0.034), RECIST (P?=?0.009), PET (P?=?0.009), and combined response (P?=?0.004) measured after pRAIT. PET had the highest predictive value with the lowest Akaike information criterion (AIC 74.26) as compared to RECIST (AIC 78.06), biomarker variation (AIC 81.94) and impact on DT (AIC 79.22). No benefit was obtained by combining the methods (AIC 78.75). This result was confirmed by the analysis of OS from MTC diagnosis.

Conclusion

¹⁸F-FDG PET appeared as the most potent and simplest prognostic method to predict survival in patients with progressive MTC treated with pRAIT. Biomarker DT before pRAIT also appeared as an independent prognostic factor, but no benefit was found by adding morphological and biomarker evaluation to PET assessment.     

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.

     

Comparison of 18F-DOPA, 18F-FDG and 68Ga-somatostatin analogue PET/CT in patients with recurrent medullary thyroid carcinoma

Purpose

To retrospectively evaluate and compare ¹⁸F-FDG, ¹⁸F-DOPA and ⁶⁸Ga-somatostatin analogues for PET/CT in patients with residual/recurrent medullary thyroid carcinoma (MTC) suspected on the basis of elevated serum calcitonin levels.

Methods

Included in the study were 18 patients with recurrent MTC in whom functional imaging with the three tracers was performed. The PET/CT results were compared on a per-patient basis and on a per-lesion-basis.

Results

At least one focus of abnormal uptake was observed on PET/CT in 13 patients with ¹⁸F-DOPA (72.2% sensitivity), in 6 patients with ⁶⁸Ga-somatostatin analogues (33.3%) and in 3 patients with ¹⁸F-FDG (16.7%) (p?18F-DOPA and ¹⁸F-FDG PET/CT (p?18F-DOPA and ⁶⁸Ga-somatostatin analogue PET/CT (p?=?0.04). Overall, 72 lesions were identified on PET/CT with the three tracers. ¹⁸F-DOPA PET/CT detected 85% of lesions (61 of 72), ⁶⁸Ga-somatostatin analogue PET/CT 20% (14 of 72) and ¹⁸F-FDG PET/CT 28% (20 of 72). There was a statistically significant difference in the number of lymph node, liver and bone lesions detected with the three tracers (p?18F-DOPA PET/CT and ¹⁸F-FDG PET/CT (p?18F-DOPA PET/CT and ⁶⁸Ga-somatostatin analogue PET/CT (p?Conclusion ¹⁸F-DOPA PET/CT seems to be the most useful imaging method for detecting recurrent MTC lesions in patients with elevated serum calcitonin levels, performing better than ¹⁸F-FDG and ⁶⁸Ga-somatostatin analogue PET/CT. ¹⁸F-FDG may complement ¹⁸F-DOPA in patients with an aggressive tumour.     

18F-FDG PET/CT-based treatment response evaluation in locally advanced rectal cancer: a prospective validation of long-term outcomes

Purpose

To prospectively evaluate the usefulness of ¹⁸F-FDG PET/CT) imaging for predicting histopathological response and long-term clinical outcomes in locally advanced rectal cancer (LARC).

Methods

This prospective study included 38 patients with a confirmed diagnosis of LARC (cT3-4 or cN+) who underwent ¹⁸F-FDG PET/CT before and after neoadjuvant therapy (NAT). Total mesorectal excision was scheduled 6 weeks after NAT and was followed by an expert histopathological analysis of the surgical specimen. Baseline variables and previously identified maximum FDG standardized uptake value (SUVmax) cut-off values before NAT (SUVmax_PRE ≥6) and after NAT (SUVmax_POST ≥2), and the absolute and percentage reductions from baseline SUVmax (?SUVmax <4 and ?SUVmax% <65 %, respectively) were applied to differentiate patients showing a metabolic tumour response from nonresponders. These features were correlated with tumour regression grade (TRG), disease-free survival (DFS) and overall survival (OS).

Results

Significantly higher 5-year DFS and OS were seen in 19 responders (TRG 3 or 4) than in 19 nonresponders (TRG 0–2; 94.4 vs. 48.8 %, p?=?0.001; 94.7 vs. 63.2 %, p?=?0.02, respectively). In multivariate analysis the only PET/CT SUVmax-based parameter significantly correlated with the likelihood of recurrence and survival was ?SUV% <65 % (HR?=?5.95, p?=?0.02, for DFS; HR?=?5.26, p?=?0.04, for OS)

Conclusion

This prospective study proved that ¹⁸F-FDG PET/CT is a valuable imaging tool for assessing rectal cancer TRG and long-term prognosis, and could potentially serve as an intermediate endpoint in treatment optimization research and rectal cancer patient care.     

Anatomical and functional volume concordance between FDG PET,and T2 and diffusion-weighted MRI for cervical cancer: a hybrid PET/MR study

Purpose

To evaluate the concordance among ¹⁸F-FDG PET imaging, MR T2-weighted (T2-W) imaging and apparent diffusion coefficient (ADC) maps with diffusion-weighted (DW) imaging in cervical cancer using hybrid whole-body PET/MR.

Methods

This study prospectively included 35 patients with cervical cancer who underwent pretreatment ¹⁸F-FDG PET/MR imaging. ¹⁸F-FDG PET and MR images were fused using standard software. The percent of the maximum standardized uptake values (SUV_max) was used to contour tumours on PET images, and volumes were calculated automatically. Tumour volumes measured on T2-W and DW images were calculated with standard techniques of tumour area multiplied by the slice profile. Parametric statistics were used for data analysis.

Results

FDG PET tumour volumes calculated using SUV_max (14.30?±?4.70) and T2-W imaging volume (33.81?±?27.32 cm³) were similar (P?>?0.05) at 35 % and 40 % of SUV_max (32.91?±?18.90 cm³ and 27.56?±?17.19 cm³ respectively) and significantly correlated (P?<?0.001; r?=?0.735 and 0.766). The mean DW volume was 30.48?±?22.41 cm³. DW volumes were not significantly different from FDG PET volumes at either 35 % SUV_max or 40 % SUV_max or from T2-W imaging volumes (P?>?0.05). PET subvolumes with increasing SUV_max cut-off percentage showed an inverse change in mean ADC values on DW imaging (P?<?0.001, ANOVA).

Conclusion

Hybrid PET/MR showed strong volume concordance between FDG PET, and T2-W and DW imaging in cervical cancer. Cut-off at 35 % or 40 % of SUV_max is recommended for ¹⁸F-FDG PET/MR SUV-based tumour volume estimation. The linear tumour subvolume concordance between FDG PET and DW imaging demonstrates individual regional concordance of metabolic activity and cell density.     

Somatostatin receptor scintigraphy with 111In-octreotide in pulmonary carcinoid tumours correlated with pathological and 18FDG PET/CT findings

Purpose

Pulmonary carcinoid (PC) tumors are rare neoplasms of the lung with good prognosis but diagnosis may be demanding since there is no exclusive modality alone to clearly differentiate a PC tumor. The purpose of this study is to establish the diagnostic features of somatostatin receptor scintigraphy (SRS), comparatively (where available) with ¹⁸FDG PET/CT (PET/CT) correlated with histopathologic findings.

Methods

Twenty-one patients who underwent SRS with ¹¹¹In-octreotide and were diagnosed as having PC tumors were retrospectively studied. Thirteen patients were performed PET/CT. Primary tumour size, Ki-67 indexes, image analysis data of SRS and PET/CT including maximum standardized uptake values (SUVmax) together with false negative, false positive, true positive and true negative lesions were documented and discussed.

Results

Eleven (52.4?%) patients were typical (TC) and 10 (47.6?%) were atypical carcinoids (AC) with mean Ki-67 indexes of 2.1 and 24?%, respectively. Patients underwent SRS for solitary pulmonary nodule (SPN) characterization (n?=?12) and determination of disease extension (n?=?9). Overall sensitivity and specificity of SRS in the detection of primary tumour, lymph nodes (LN) and distant metastasis (DM) were 76 and 97?%, respectively, whereas, positive and negative predictive values were 95 and 86?%. PET/CT was performed for determining disease spread (n?=?3) and metabolic characterization (n?=?10) of SPNs. Mean SUVmax in the primary pulmonary lesion in TCs and ACs were 2.9?±?0.8 and 7.9?±?5.4, respectively. Nodal involvement (n?=?5) and DM (n?=?3) were also detected. Sensitivity and specificity of PET/CT in the detection of primary tumour, LNs and DM were 85 and 89.4?%, respectively.

Conclusion

SRS is useful in the diagnosis and monitoring of PC tumors when incorporated with ¹⁸FDG PET/CT as a primary staging tool particularly in the determination of disease spread.