In vivo assessment of safety, biodistribution, and radiation dosimetry of the [18F]Me4FDG PET-radiotracer in adults.

BACKGROUND: Approaches targeting the sodium-glucose cotransporter (SGLT) could represent a promising future therapeutic strategy for numerous oncological and metabolic diseases. In this study, we evaluated the safety, biodistribution and radiation dosimetry of the glucose analogue positron emission tomography (PET) agent [18F] labeled alpha-methyl-4-deoxy-4-[18F]fluoro-D-glucopyranoside ([18F]Me4FDG) with high sodium-glucose cotransporter and low glucose transporter (GLUT) affinity. For this purpose, five healthy volunteers (1 man, 4 women) underwent multiple whole-body PET/computed tomography (CT) examinations starting with injection and up to 4 h after injection of averaged (2.4 ± 0.1) MBq/kg (range: 2.3-2.5 MBq/kg) administered activity. The PET/CT scans were conducted in 5 separate sessions, blood pressure and temperature were measured, and blood and urine samples were collected before the scans and one hour after injection to assess toxicity. Measurements of [18F]Me4FDG radioactivity in organs of interest were determined from the PET/CT scans at 5 time points. Internal dosimetry was performed on voxel level using a fast Monte Carlo approach. RESULTS: All studied volunteers could well tolerate the [18F]Me4FDG and no adverse event was reported. The calculated effective dose was (0.013 ± 0.003) mSv/MBq. The organs with the highest absorbed dose were the kidneys with 0.05 mSv/MBq per kidney. The brain showed almost no uptake. After 60 min, (12 ± 15) % of the administered dose was excreted into the bladder. CONCLUSION: Featuring an effective dose of only 0.013 ± 0.003 mSv/MBq and no occurrence of side effects, the glucose analogue [18F]Me4FDG seems to be a safe radio-tracer with a favorable biodistribution for PET imaging and also within several consecutive scans. TRIAL REGISTRATION NUMBER: NCT03557138, Registered 22 February 2017, https://ichgcp.net/clinical-trials-registry/NCT03557138 .

FAPi PET/CT for assessment and visualisation of active myositis-related interstitial lung disease: a prospective observational pilot study.

Background: Interstitial lung disease (ILD) is a common manifestation of idiopathic inflammatory myopathies (IIM) and a substantial contributor to hospitalisation, increased morbidity, and mortality. In-vivo evidence of ongoing tissue remodelling in IIM-ILD is scarce. We aimed to evaluate fibroblast activation in lungs of IIM-patients and control individuals using 68Ga-labelled inhibitor of Fibroblast-Activation-Protein (FAPi) based positronic emission tomography and computed tomography imaging (PET/CT). Methods: In this prospective observational pilot study, consecutive patients with IIM and participants without rheumatic conditions or ILD serving as a control group were recruited at the Medical University of Vienna, Austria, and underwent FAPi PET/CT imaging. Standard-of-care procedures including clinical examination, assessment of severity of dyspnoea, high-resolution computed tomography (HR-CT), and pulmonary function testing (PFT) were performed on all patients with IIM at baseline and for patients with IIM-ILD at follow-up of 12 months. Baseline pulmonary FAPi-uptake was assessed by the maximum (SUVmax) and mean (SUVmean) standardized uptake values (SUV) over the whole lung (wl). SUV was corrected for blood pool background activity and target-to-background ratios (TBR) were calculated. We compared pulmonary FAPi-uptake between patients with IIM-ILD and those without ILD, as well as controls, and correlated baseline FAP-uptake with standard diagnostic tools such as HR-CT and PFT. For predictive implications, we investigated whether patients with IIM and progressive ILD exhibited higher baseline FAPi-uptake compared to those with stable ILD. Metrics are reported as mean with standard deviation (±SD). Findings: Between November 16, 2021 and October 10, 2022, a total of 32 patients were enrolled in the study. Three participants from the control group were excluded due to cardiopulmonary disease. In individuals with IIM-ILD (n = 14), wlTBRmax and wlTBRmean were significantly increased as compared with both non-ILD-IIM patients (n = 5) and the control group (n = 16): wlTBRmax: 2.06 ± 1.04 vs. 1.04 ± 0.22 (p = 0.019) and 1.08 ± 0.19 (p = 0.0012) and wlTBRmean: 0.45 ± 0.19 vs. 0.26 ± 0.06 (p = 0.025) and 0.27 ± 0.07 (p = 0.0024). Similar values were observed in wlTBRmax or wlTBRmean between non-ILD IIM patients and the control group. Patients with progressive ILD displayed significantly enhanced wlTBRmax and wlTBRmean values at baseline compared to patients with stable ILD: wlTBRmax: 1.30 ± 0.31 vs. 2.63 ± 1.04 (p = 0.0084) and wlTBRmean: 0.32 ± 0.08 vs. 0.55 ± 0.19 (p = 0.021). Strong correlations were found between FAPi-uptake and disease extent on HR-CT (wlTBRmax: R = 0.42, p = 0.07; wlTBRmean: R = 0.56, p = 0.013) and severity of respiratory symptoms determined by the New York Heart Association (NYHA) classification tool (wlTBRmax: R = 0.52, p = 0.022; wlTBRmean: R = 0.59, p = 0.0073). Further, pulmonary FAPi-uptake showed inverse correlation with forced vital capacity (FVC) (wlTBRmax: R = -0.56, p = 0.012; wlTBRmean: R = -0.64, p = 0.0033) and diffusing capacity of the lungs for carbon monoxide (DLCO) (wlTBRmax: R = -0.52, p = 0.028; wlTBRmean: R = -0.68, p = 0.0017). Interpretation: Our study demonstrates higher fibroblast activation in patients with IIM-ILD compared to non-ILD patients and controls. Intensity of pulmonary FAPi accumulation was associated with progression of ILD. Considering that this study was carried out on a small population, FAPi PET/CT may serve as a useful non-invasive tool for risk stratification of lung disease in IIM. Funding: The Austrian Research Fund.

Induction of Arterial Inflammation by Immune Checkpoint Inhibitor Therapy in Lung Cancer Patients as Measured by 2-[18F]FDG Positron Emission Tomography/Computed Tomography Depends on Pre-Existing Vascular Inflammation.

BACKGROUND: Immune checkpoint inhibitors (ICI) are one of the most effective therapies in oncology, albeit associated with various immune-related adverse events also affecting the cardiovascular system. METHODS: We aimed to investigate the effect of ICI on arterial 2-[18F]FDG uptake by using 2-[18F]FDG PET/CT imaging pre/post treatment in 47 patients with lung cancer. Maximum 2-[18F]FDG standardized uptake values (SUVmax) and target-to-background ratios (TBRs) were calculated along six arterial segments. We classified the arterial PET lesions by pre-existing active inflammation (cut-off: TBRpre ≥ 1.6). 2-[18F]FDG metabolic activity pre/post treatment was also quantified in bone marrow, spleen, and liver. Circulating blood biomarkers were additionally collected at baseline and after immunotherapy. RESULTS: ICI treatment resulted in significantly increased arterial inflammatory activity, detected by increased TBRs, in all arterial PET lesions analyzed. In particular, a significant elevation of arterial 2-[18F]FDG uptake was only recorded in PET lesions without pre-existing inflammation, in calcified as well as in non-calcified lesions. Furthermore, a significant increase in arterial 2-[18F]FDG metabolic activity after immunotherapy was solely observed in patients not previously treated with chemotherapy or radiotherapy as well as in those without CV risk factors. No significant changes were recorded in either 2-[18F]FDG uptake of bone marrow, spleen and liver after treatment, or the blood biomarkers. CONCLUSIONS: ICI induces vascular inflammation in lung cancer patients lacking pre-existing arterial inflammation.

Direct Patlak Reconstruction of [68Ga]Ga-PSMA PET for the Evaluation of Primary Prostate Cancer Prior Total Prostatectomy: Results of a Pilot Study.

To investigate the use of kinetic parameters derived from direct Patlak reconstructions of [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) to predict the histological grade of malignancy of the primary tumor of patients with prostate cancer (PCa). Thirteen patients (mean age 66 ± 10 years) with a primary, therapy-naïve PCa (median PSA 9.3 [range: 6.3-130 µg/L]) prior radical prostatectomy, were recruited in this exploratory prospective study. A dynamic whole-body [68Ga]Ga-PSMA-11 PET/CT scan was performed for all patients. Measured quantification parameters included Patlak slope (Ki: absolute rate of tracer consumption) and Patlak intercept (Vb: degree of tracer perfusion in the tumor). Additionally, the mean and maximum standardized uptake values (SUVmean and SUVmax) of the tumor were determined from a static PET 60 min post tracer injection. In every patient, initial PSA (iPSA) values that were also the PSA level at the time of the examination and final histology results with Gleason score (GS) grading were correlated with the quantitative readouts. Collectively, 20 individual malignant prostate lesions were ascertained and histologically graded for GS with ISUP classification. Six lesions were classified as ISUP 5, two as ISUP 4, eight as ISUP 3, and four as ISUP 2. In both static and dynamic PET/CT imaging, the prostate lesions could be visually distinguished from the background. The average values of the SUVmean, slope, and intercept of the background were 2.4 (±0.4), 0.015 1/min (±0.006), and 52% (±12), respectively. These were significantly lower than the corresponding parameters extracted from the prostate lesions (all p < 0.01). No significant differences were found between these values and the various GS and ISUP (all p > 0.05). Spearman correlation coefficient analysis demonstrated a strong correlation between static and dynamic PET/CT parameters (all r ≥ 0.70, p < 0.01). Both GS and ISUP grading revealed only weak correlations with the mean and maximum SUV and tumor-to-background ratio derived from static images and dynamic Patlak slope. The iPSA demonstrated no significant correlation with GS and ISUP grading or with dynamic and static PET parameter values. In this cohort of mainly high-risk PCa, no significant correlation between [68Ga]Ga-PSMA-11 perfusion and consumption and the aggressiveness of the primary tumor was observed. This suggests that the association between SUV values and GS may be more distinctive when distinguishing clinically relevant from clinically non-relevant PCa.

Comparison of cardiac image-derived input functions for quantitative whole body [18F]FDG imaging with arterial blood sampling.

Introduction: Dynamic positron emission tomography (PET) and the application of kinetic models can provide important quantitative information based on its temporal information. This however requires arterial blood sampling, which can be challenging to acquire. Nowadays, state-of-the-art PET/CT systems offer fully automated, whole-body (WB) kinetic modelling protocols using image-derived input functions (IDIF) to replace arterial blood sampling. Here, we compared the validity of an automatic WB kinetic model protocol to the reference standard arterial input function (AIF) for both clinical and research settings. Methods: Sixteen healthy participants underwent dynamic WB [18F]FDG scans using a continuous bed motion PET/CT system with simultaneous arterial blood sampling. Multiple processing pipelines that included automatic and manually generated IDIFs derived from the aorta and left ventricle, with and without motion correction were compared to the AIF. Subsequently generated quantitative images of glucose metabolism were compared to evaluate performance of the different input functions. Results: We observed moderate to high correlations between IDIFs and the AIF regarding area under the curve (r = 0.49-0.89) as well as for the cerebral metabolic rate of glucose (CMRGlu) (r = 0.68-0.95). Manual placing of IDIFs and motion correction further improved their similarity to the AIF. Discussion: In general, the automatic vendor protocol is a feasible approach for the quantification of CMRGlu for both, clinical and research settings where expertise or time is not available. However, we advise on a rigorous inspection of the placement of the volume of interest, the resulting IDIF, and the quantitative values to ensure valid interpretations. In protocols requiring longer scan times or where cohorts are prone to involuntary movement, manual IDIF definition with additional motion correction is recommended, as this has greater accuracy and reliability.

Whole-body metabolic connectivity framework with functional PET.

The nervous and circulatory system interconnects the various organs of the human body, building hierarchically organized subsystems, enabling fine-tuned, metabolically expensive brain-body and inter-organ crosstalk to appropriately adapt to internal and external demands. A deviation or failure in the function of a single organ or subsystem could trigger unforeseen biases or dysfunctions of the entire network, leading to maladaptive physiological or psychological responses. Therefore, quantifying these networks in healthy individuals and patients may help further our understanding of complex disorders involving body-brain crosstalk. Here we present a generalized framework to automatically estimate metabolic inter-organ connectivity utilizing whole-body functional positron emission tomography (fPET). The developed framework was applied to 16 healthy subjects (mean age ± SD, 25 ± 6 years; 13 female) that underwent one dynamic 18F-FDG PET/CT scan. Multiple procedures of organ segmentation (manual, automatic, circular volumes) and connectivity estimation (polynomial fitting, spatiotemporal filtering, covariance matrices) were compared to provide an optimized thorough overview of the workflow. The proposed approach was able to estimate the metabolic connectivity patterns within brain regions and organs as well as their interactions. Automated organ delineation, but not simplified circular volumes, showed high agreement with manual delineation. Polynomial fitting yielded similar connectivity as spatiotemporal filtering at the individual subject level. Furthermore, connectivity measures and group-level covariance matrices did not match. The strongest brain-body connectivity was observed for the liver and kidneys. The proposed framework offers novel opportunities towards analyzing metabolic function from a systemic, hierarchical perspective in a multitude of physiological pathological states.

Value of 68Ga-labeled bombesin antagonist (RM2) in the detection of primary prostate cancer comparing with [18F]fluoromethylcholine PET-CT and multiparametric MRI-a phase I/II study.

OBJECTIVES: The bombesin derivative RM2 is a GRPr antagonist with strong binding affinity to prostate cancer (PCa). In this study, the impact of [68Ga]Ga-RM2 positron emission tomography-computed tomography (PET-CT) for the detection of primary PCa was compared with that of [18F]FCH PET-CT and multiparametric magnetic resonance imaging (mpMRI). METHODS: This phase I/II study was conducted in 30 biopsy-positive PCa subjects. The patients were stratified into high (10 patients), intermediate (10 patients), and low risk (10 patients) for extraglandular metastases as defined by National Comprehensive Cancer Network (NCCN) criteria (NCCN Clinical Practice Guidelines in Oncology, 2016). The prostate gland was classified in 12 anatomic segments for data analysis of the imaging modalities as well as histopathologic findings. The segment with the highest radiotracer uptake was defined as the "index lesion." All cases were scheduled to undergo prostatectomy with pelvic lymph node (LN) dissection in intermediate- and high-risk patients. Intraprostatic and pelvic nodal [68Ga]Ga-RM2 and [18F]FCH PET-CT findings were correlated with mpMRI and histopathologic results. RESULTS: Of the 312 analyzed regions, 120 regions (4 to 8 lesions per patient) showed abnormal findings in the prostate gland. In a region-based analysis, overall sensitivity and specificity of [68Ga]Ga-RM2 PET-CT in the detection of primary tumor were 74% and 90%, respectively, while it was 60% and 80% for [18F]FCH PET-CT and 72% and 89% for mpMRI. Although the overall sensitivity of [68Ga]Ga-RM2 PET-CT was higher compared to that of [18F]FCH PET-CT and mpMRI, the statistical analysis showed only significant difference between [68Ga]Ga-RM2 PET-CT and [18F]FCH PET-CT in the intermediate-risk group (p = 0.01) and [68Ga]Ga-RM2 PET-CT and mpMRT in the high-risk group (p = 0.03). In the lesion-based analysis, there was no significant difference between SUVmax of [68Ga]Ga-RM2 and [18F]FCH PET-CT in the intraprostatic malignant lesions ([68Ga]Ga-RM2: mean SUVmax: 5.98 ± 4.13, median: 4.75; [18F]FCH: mean SUVmax: 6.08 ± 2.74, median: 5.5; p = 0.13). CONCLUSIONS: [68Ga]Ga-RM2 showed promising PET tracer for the detection of intraprostatic PCa in a cohort of patients with different risk stratifications. However, significant differences were only found between [68Ga]Ga-RM2 PET-CT and [18F]FCH PET-CT in the intermediate-risk group and [68Ga]Ga-RM2 PET-CT and mpMRT in the high-risk group. In addition, GRP-R-based imaging seems to play a complementary role to choline-based imaging for full characterization of PCa extent and biopsy guidance in low- and intermediate-metastatic-risk PCa patients and has the potential to discriminate them from those at higher risks. KEY POINTS: • [68Ga]Ga-RM2 is a promising PET tracer with a high detection rate for intraprostatic PCa especially in intermediate-risk prostate cancer patients. • GRPr-based imaging seems to play a complementary role to choline-based or PSMA-based PET/CT imaging in selected low- and intermediate-risk PCa patients for better characterization and eventually biopsy guidance of prostate cancer disease.

Diagnostic Value of 2-[18F]FDG PET/CT in a Patient with Atypical Subacute Thyroiditis: A Case Report.

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) imaging with 2-deoxy-2-[18F]fluoro-d-glucose (2-[18F]FDG) is a sensitive diagnostic imaging modality in oncology and could be a useful diagnostic tool in patients with fever of unknown origin (FUO) or with inflammation of unknown origin (IUO). CASE PRESENTATION: We report a case of a patient originally presenting with a clinical history of FUO and later with persistent high-sensitivity C-reactive protein (hsCRP) levels, even after antibiotic therapy. The patient underwent 2-[18F]FDG PET/CT to investigate and to localize a possible focus of infection or inflammation. 2-[18F]FDG hotspots were detected in both thyroid lobes. Thyroid diagnostic examinations and follow up were performed. Subacute thyroiditis (SAT) was then diagnosed by thyroid examinations, and other possible causes of FUO or IUO were not found. CONCLUSION: This case illustrates the potential diagnostic value of 2-[18F]FDG PET/CT in patients with atypical SAT, who originally present with only a clinical history of FUO.

Response and Toxicity to the Second Course of 3 Cycles of 177Lu-PSMA Therapy Every 4 Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: We investigated the response rate and degree of toxicity of a second course of three cycles of [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) every 4 weeks in mCRPC patients. METHODS: Forty-three men (71.5 ± 6.6 years, median PSA 40.8 (0.87-1358 µg/L)) were studied. The response was based on the PSA level 4 weeks after the third cycle. The laboratory parameters before and one month after the last cycle were compared. Kaplan-Meier methods were used to estimate the progression-free survival (PFS) and overall survival (OS), and the Cox regression model was performed to find predictors of survival. RESULTS: Twenty-six patients (60.5%) exhibited a PSA reduction (median PSA declined from 40.8 to 20.2, range 0.6-1926 µg/L, p = 0.002); 18 (42%) and 8 (19%) patients showed a PSA decline of ≥50% and ≥80%, respectively. The median OS and PFS were 136 and 31 weeks, respectively. The patients with only lymph node metastases survived longer (p = 0.02), whereas the patients with bone metastases had a shorter survival (p = 0.03). In the multivariate analysis, only the levels of PSA prior to the therapy remained significant for OS (p < 0.05, hazard ratio 2.43, 95% CI 1.01-5.87). The levels of hemoglobin (11.5 ± 1.7 g/dL vs. 11 ± 1.6 g/dL, p = 0.006) and platelets (208 ± 63 g/L vs. 185 ± 63 g/L, p = 0.002) significantly decreased one month after cycle three, though only two grade 3 anemia and one grade 3 thrombocytopenia were recorded. CONCLUSION: A further intensive PSMA-RLT course is well tolerated in mCRPC patients and associated with promising response rates and OS.

Additional Value of 2-[18F]FDG PET/CT Comparing to MRI in Treatment Approach of Anal Cancer Patients.

Accurate staging and treatment planning are imperative for precise management in Anal Cancer (ACa) patients. We aimed to evaluate the additive and prognostic value of pre-treatment 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) in the staging and management of ACa compared to magnetic resonance imaging (MRI). This retrospective study was conducted on 54 patients. Pre-treatment 2-[18F]FDG PET/CT studies and MRI reports were compared considering the primary tumor, pelvic lymph nodes, and metastatic lesions. The impact of 2-[18F]FDG PET/CT in the management and its prognostic value, using maximum standardized uptake value (SUVmax), were assessed. Discordant findings were found in 46.3% of patients (5 in T; 1 in T and N; 18 in N; and 1 in M stage). 2-[18F]FDG PET/CT resulted in up-staging in 9.26% and down-staging in 3.7% of patients. Perirectal lymph nodes were metabolically inactive in 12.9% of patients. Moreover, 2-[18F]FDG PET/CT resulted in management change in 24.1% of patients. Finally, SUVmax provided no prognostic value. 2-[18F]FDG PET/CT altered staging and management in a sizable number of patients in this study, and supports a need for a change in guidelines for it to be used as a routine complementary test in the initial management of ACa.

Diagnostic Performance of [18F]Fluorocholine and [68Ga]Ga-PSMA PET/CT in Prostate Cancer: A Comparative Study.

The current study endeavored to closely compare the detection rate of 68-Gallium labelled prostate-specific membrane antigen ([68Ga]Ga-PSMA) versus [18F]Fluorocholine in men with prostate cancer (PC), to investigate the benefits and pitfalls of each modality in the setting of various patient characteristics. We retrospectively analyzed 29 biopsy-proven PC patients in two categories, staging and restaging, who underwent both scans within a maximum of 30 days of each other. Variables including patient demographics, prostate specific antigen (PSA) level, Gleason score, clinical course, and following treatments were recorded. The number and location of suspicious lesions as well as uptake values were noted. A total of 148 suspicious lesions were detected, of which 70.9% (105/148) were concordantly visualized in both imaging modalities. [68Ga]Ga-PSMA positron emission tomography/computed tomography (PET/CT) revealed a higher number of metastatic lesions per patients (91% vs 78%). The mean of maximum standardized uptake value (SUV max) in concordant lesions was significantly higher in [68Ga]Ga-PSMA compared to [18F]Fluorocholine PET/CT (14.6 ± 8.44 vs. 6.9 ± 3.4, p = 0.001). Discordant lesions were detected by both modalities, but more frequently by [68Ga]Ga-PSMA PET/CT (20.3% in [68Ga]Ga-PSMA versus 8.8% by [18F]Fluorocholine PET/CT). In patients with PSA levels below 1.0 ng/mL and <2.0 ng/mL, [18F]Fluorocholine PET/CT detection rate was half (57% and 55%, respectively) that of [68Ga]Ga-PSMA PET/CT. Tumor, nodes and metastases (TNM) staging, and subsequently patient management, was only influenced in 4/29 patients (14%), particularly by [68Ga]Ga-PSMA PET/CT with PSA values under 0.5 ng/mL. [68Ga]Ga-PSMA PET/CT revealed superior diagnostic performance to [18F]Fluorocholine PET/CT in staging and restaging of PC patients, especially in cases with low PSA levels. However, in a few hormone resistant high-risk PC patients, [18F]Fluorocholine PET/CT may improve overall diagnostic accuracy.

Impact of contemporary therapy- concepts on surgical morbidity in breast cancer patients: A retrospective single center analysis of 829 patients.

INTRODUCTION: Morbidity after breast cancer surgery remains low with revision surgery below 5%. This retrospective monocentric study investigates whether new methods like neoadjuvant chemotherapy (nCT), oncoplastic surgery (OPS) or intraoperative radiotherapy (IORT) affect overall morbidity. In addition, we sought to determine a possible effect of morbidity on oncologic outcome. METHODS: Clinical Data from all breast cancer cases, operated at the OnkoZert"- certified Breast Health Center of the "Sisters of Charity Hospital" in Linz between 2011 and 2014, were evaluated. Age (≤/>70), nCT, IORT, surgical technique and histological subtypes were analyzed concerning their impact on morbidity. Overall survival (OS) and disease-free survival (DFS) were assessed by Kaplan-Meier estimates. RESULTS: 829 patients were included, 24% were older than 70y, 19% underwent oncoplasty, 5.5% immediate reconstruction, 17% of the invasive cancers were treated with nCT and 4.1% received IORT. One or more complications occurred in 83 patients (10%), while 62 patients (7.5%) underwent revision surgery. Univariate analysis showed that mastectomy and age >70 doubled the risk of surgical morbidity. Multivariate regression analysis identified age >70 as the only independent prognostic parameter for the occurrence of morbidity (OR: 2.42, 95% CI: 1.41-4.1, p = 0,00134). Morbidity was not associated with worse oncologic outcome in terms of OS or DFS. SUMMARY: In our patient collective, modern techniques such as nCT, OPS or IORT did not influence surgical morbidity rates. Those were only increased by patient's age. Additionally, surgical morbidity did not show any significant impact on OS and DFS.

Multiphasic 68Ga-PSMA PET/CT in the Detection of Early Recurrence in Prostate Cancer Patients with a PSA Level of Less Than 1 ng/mL: A Prospective Study of 135 Patients.

The main objective of this prospective study was to determine the impact of multiphasic acquisition of 68Ga-PSMA PET/CT in the detection of recurrent prostate cancer in the early stage of biochemical recurrence with a prostate-specific antigen (PSA) level of less than 1 ng/mL. Also, 68Ga-PSMA PET/CT positivity was correlated with clinical parameters for the assessment of predictive markers. Methods: A prospective monocentric study was conducted on 135 prostate cancer patients with biochemical recurrence and a PSA level of less than 1 ng/mL. All patients had undergone initial prostatectomy, with additional radiation therapy in 19.3% of patients and androgen-deprivation therapy in 7.4%. The patients underwent dynamic acquisitions from the prostate bed (1-8 min after injection), standard whole-body acquisitions (60 min after injection), and limited-bed-position delayed acquisitions (120-150 min after injection). The studies were reviewed by 2 board-certified nuclear medicine specialists, independently. A combination of visual and semiquantitative analyses and correlation with morphologic (e.g., MRI) or clinical follow-up findings was used for the final interpretation of lesions as benign or malignant. 68Ga-prostate-specific membrane antigen (PSMA) PET/CT positivity was also correlated with primary clinical findings. Results: Incorporating the information from all phases, we were able to detect 116 lesions in 49.6% of patients (22 local recurrences, 63 lymph nodes, and 31 distant metastases). The detection rates were 31.8%, 44.9%, and 71.4% for PSA < 0.2 ng/mL, 0.2 ≤ PSA < 0.5, and 0.5 ≤ PSA < 1, respectively. Additional dynamic or delayed phases resulted in better determination of equivocal lesions and a higher diagnostic performance in 25.9% of patients. Stand-alone dynamic and delayed images led to better interpretation of equivocal findings in the prostate bed (31.4%) and in other lesions (lymph node or bone) (20%), respectively. Conclusion:68Ga-PSMA PET/CT showed promise for early detection of recurrent disease in patients with a PSA level of 0.5-1.0 ng/mL. However, it showed limited value in patients with a PSA level of less than 0.5 ng/mL. Multiphasic 68Ga-PSMA PET/CT led to a better determination of equivocal findings. Although dynamic images may provide helpful information for assessment of the prostate bed, delayed acquisitions seem to have a greater impact in clarifying equivocal findings.

Molecular imaging of bone metastases using tumor-targeted tracers.

Bone metastasis is a disastrous manifestation of most malignancies, especially in breast, prostate and lung cancers. Since asymptomatic bone metastases are not uncommon, early detection, precise assessment, and localization of them are very important. Various imaging modalities have been employed in the setting of diagnosis of bone metastasis, from plain radiography and bone scintigraphy to SPECT, SPECT/CT, PET/CT, MRI. However, each modality showed its own limitation providing accurate diagnostic performance. In this regard, various tumor-targeted radiotracers have been introduced for molecular imaging of bone metastases using modern hybrid modalities. In this article we review the strength of different cancer-specific radiopharmaceuticals in the detection of bone metastases. As shown in the literature, among various tumor-targeted tracers, 68Ga DOTA-conjugated-peptides, 68Ga PSMA, 18F DOPA, 18F galacto-RGD integrin, 18F FDG, 11C/18F acetate, 11C/18F choline, 111In octreotide, 123/131I MIBG, 99mTc MIBI, and 201Tl have acceptable capabilities in detecting bone metastases depending on the cancer type. However, different study designs and gold standards among reviewed articles should be taken into consideration.

[Imaging of parathyroid adenomas with F­18 choline PET-CT]. / Darstellung und Lokalisation von Nebenschilddrüsenadenomen mit F­18 Cholin PET/CT.

BACKGROUND: Ultrasound and sestamibi scintigraphy are the recommended standard procedures for initial diagnosis in primary hyperparathyroidism (pHPT). Recently, F­18 choline positron emission tomography computed tomography (choline PET/CT) has been shown promising results for the diagnostic work up of primary hyperparathyroidism (pHPT) suggesting superiority over conventional scintigraphy using Tc99m sestamibi based protocols using planar dual-phase imaging, SPECT or SPECT/CT. METHODS: This review presents the results of F­18 choline PET/CT on the basis of a literature search using the keywords "primary hyperparathyroidism and choline", "primary hyperparathyroidism and PET", "parathyroid adenoma and choline" und "parathyroid adenoma and PET". RESULTS: 6 studies were identified dealing with the diagnostic impact of choline PET/CT. The studies included 5 to 151 patients. Localization of single gland adenomas can be achieved with choline PET/CT in 80 up to 96% of cases. A high sensitivity and accuracy of choline PET/CT imaging is documented even in cases of repeated surgery for recurrent pHPT, in coexistant nodular goiter or in the detection of adenoma in atypical localization. CONCLUSIONS: Using choline PET/CT parathyroid adenoma and probably parathyroid hyperplasia can be exactly localized in most patients with pHPT. Thus, a minimal-invasive surgical procedure is feasible with decreased risk of complications but high success rate in terms of biochemical cure. The diagnostic accuracy in multiglandular disease remains to be established.

18F-Fluorocholine PET/CT in the assessment of primary hyperparathyroidism compared with 99mTc-MIBI or 99mTc-tetrofosmin SPECT/CT: a prospective dual-centre study in 100 patients.

PURPOSE: In this prospective study we compared the accuracy of 18F-fluorocholine PET/CT with that of 99mTc-MIBI or99mTc-tetrofosmin SPECT/CT in the preoperative detection of parathyroid adenoma in patients with primary hyperparathyroidism. We also assessed the value of semiquantitative parameters in differentiating between parathyroid hyperplasia and adenoma. METHODS: Both 18F-fluorocholine PET/CT and 99mTc-MIBI/tetrofosmin SPECT/CT were performed in 100 consecutive patients with biochemical evidence of primary hyperparathyroidism. At least one abnormal focus on either 18F-fluorocholine or 99mTc-MIBI/tetrofosmin corresponding to a parathyroid gland or ectopic parathyroid tissue was considered as a positive finding. In 76 patients with positive findings on at least one imaging modality, surgical exploration was performed within 6 months, and the results were related to histopathological findings and clinical and laboratory findings at 3-6 months as the standard of truth. In 24 patients, no surgery was performed: in 18 patients with positive imaging findings surgery was refused or considered risky, and in 6 patients imaging was negative. Therefore, data from 82 patients (76 undergoing surgery, 6 without surgery) in whom the standard of truth criteria were met, were used in the final analysis. RESULTS: All patients showed biochemical evidence of primary hyperparathyroidism with a mean serum calcium level of 2.78 ± 0.34 mmol/l and parathormone (PTH) level of 196.5 ± 236.4 pg/ml. The study results in 76 patients with verified histopathology and 3 patients with negative imaging findings were analysed. Three of six patients with negative imaging showed normalized serum PTH and calcium levels on laboratory follow-up at 3 and 6 months, and the results were considered true negative. In a patient-based analysis, the detection rate with 18F-fluorocholine PET/CT was 93% (76/82), but was only 61% (50/82) with 99mTc-MIBI/tetrofosmin SPECT/CT. In a lesion-based analysis, the sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of 18F-fluorocholine PET/CT in the detection of parathyroid adenoma were 93.7%, 96.0%, 90.2%, 97.4% and 95.3%, respectively, and of 99mTc-MIBI/tetrofosmin SPECT/CT were 60.8%, 98.5%, 94.1%, 86.3% and 87.7%, respectively. Although 18F-fluorocholine PET-positive adenomatous lesions showed higher SUVmax values than the hyperplastic glands (6.80 ± 3.78 vs. 4.53 ± 0.40) in the semiquantitative analysis, the difference was not significant (p = 0.236). The mean size (measured as the length of the greatest dimension) and weight of adenomas were 15.9 ± 7.6 mm (median 15 mm, range 1-40 mm) and 1.71 ± 1.86 g (median 1 g, range: 0.25-9 g), respectively. Among the analysed parameters including serum calcium and PTH and the size and weight of parathyroid adenomas, size was significantly different between patients with negative 99mTc-MIBI/tetrofosmin SPECT/CT and those with positive 99mTc-MIBI/tetrofosmin SPECT/CT (mean size 13.4 ± 7.6 mm vs. 16.9 ± 7.4 mm, respectively; p = 0.042). CONCLUSION: In this prospective study, 18F-fluorocholine PET/CT showed promise as a functional imaging modality, being clearly superior to 99mTc-MIBI/tetrofosmin SPECT/CT, especially in the detection and localization of small parathyroid adenomas in patients with primary hyperparathyroidism. SUVmax was higher in parathyroid adenomas than in hyperplasia. However, further evaluation of this modality is needed.

Optimal time-point for 68Ga-PSMA-11 PET/CT imaging in assessment of prostate cancer: feasibility of sterile cold-kit tracer preparation?

PURPOSE: In this prospective study, we evaluated the optimal time-point for 68Ga-PSMA-11 PET/CT acquisition in the assessment of prostate cancer. We also examined, for the first time the feasibility of tracer production using a PSMA-11 sterile cold-kit in the clinical workflow of PET/CT centres. METHODS: Fifty prostate cancer patients (25 staging, 25 biochemical recurrence) were enrolled in this study. All patients received an intravenous dose of 2.0 MBq/kg body weight 68Ga-PSMA-11 prepared using a sterile cold kit (ANMI SA, Liege, Belgium), followed by an early (20 min after injection) semi-whole-body PET/CT scan and a standard-delay (100 min after injection) abdominopelvic PET/CT scan. The detection rates with 68Ga-PSMA-11 were compared between the two acquisitions. The pattern of physiological background activity and tumour to background ratio were also analysed. RESULTS: The total preparation time was reduced to 5 min using the PSMA-11 sterile cold kit, which improved the final radionuclide activity by about 30% per single 68Ge/68Ga generator elution. Overall, 158 pathological lesions were analysed in 45 patients (90%) suggestive of malignancy on both (early and standard-delay) 68Ga-PSMA PET/CT images. There was a significant (p < 0.001) increase in SUVmax on delayed images in suspicious prostates (11.6 ± 8.2 to 14.8 ± 1.0) and lymph nodes (LNs; 9.7 ± 5.9 to 12.3 ± 8.8), while bone lesions showed no significant increase (8.5 ± 5.6 to 9.2 ± 7.0, p = 0.188). However, the SUVmax of suspicious lesions on early images was adequate to support the criteria for correct interpretation (mean SUVmax 9.83 ± 6.7).In 26 of 157 lesions, but a decrease in SUV was seen, mostly in subcentimetre lesions in patients with multiple metastases. However, it did not affect the staging of the disease or patient management. The tumour to background ratio of primary prostate lesions and LNs showed a significant (p < 0.001) increase from the early to the standard-delay acquisition, but no significant increase was seen in bony lesions (p = 0.11). CONCLUSION: The PSMA-11 sterile cold kit seems to be feasible for use in routine clinical practice, and it has a shorter radionuclide preparation time and is less operator-dependent than the synthesizer-based production method. In addition, early 68Ga-PSMA-11 PET/CT imaging seems to provide a detection rate comparable with that of standard-delay imaging. Furthermore, the shorter preparation time using the 68Ga-PSMA-11 sterile cold kit and promising value of early PET/CT scanning could allow tailoring of imaging protocols which may reduce the costs and improve the time efficiency in PET/CT centres.

Role of Pepsin and Oropharyngeal pH-Monitoring to Assess the Postoperative Outcome of Patients with Laryngopharyngeal Reflux: Results of a Pilot Trial.

BACKGROUND: The aim of this study was to evaluate the value of salivary pepsin and oropharyngeal pH-monitoring to assess the surgical outcome of patients with laryngopharyngeal reflux (LPR). MATERIALS AND METHODS: Twenty consecutive patients with LPR despite proton pump inhibitor treatment received laparoscopic antireflux surgery. Twenty-four hour esophageal pH-monitoring (multichannel intraluminal impedance monitoring [MII]-pH) and esophageal manometry (high-resolution manometry) data were documented preoperatively and at 3-month follow-up. An ears, nose and throat (ENT) examination was performed, including assessment of Belafsky Reflux Finding Score (RFS). Clinical symptoms were evaluated with the Belafsky Reflux Symptom Index (RSI) and the Gastrointestinal Quality of Life Index (GIQLI). Simultaneous to the MII-pH and collection of saliva samples, detection of oropharyngeal reflux events was performed. Treatment failure was defined as postoperative pathologic RFS or RSI score and improvement of GIQLI of <10 points, despite showing a normal DeMeester score. RESULTS: At baseline, all patients had a pathological ENT examination, RSI score, and MII-pH data. All patients showed postoperatively a normal DeMeester score (mean 6.39 ± 4.87). Five patients were defined as treatment failures with a change of pepsin concentration from median 157.0 (95% confidence interval [CI]: 0-422) to 180.7 (95% CI: 0-500). In patients defined as treatment success, median pepsin value decreased from 206.3 (95% CI: 89-278) to 76.0 (95% CI: 55-205); (P = .093). Oropharyngeal pH-monitoring data showed no significant change in both groups. CONCLUSION: Salivary pepsin could be a marker for treatment success, while oropharyngeal pH-monitoring seems to be inadequate in these terms. However, larger studies are required to reach firm conclusions.

Therapy assessment of bone metastatic disease in the era of 223radium.

PURPOSE: Defining an optimal imaging modality for assessment of therapy and the best time of evaluation are pivotal for ideal patient's management. METHODS: 223Ra (Xofigo®, formerly Alpharadin) has been approved by the FDA and European Medicines Agency for treatment of metastatic castration-resistant prostate cancer with painful osseous involvement. RESULTS: PET/CT imaging using various radiotracers such as 18F-FDG, 18F-FCH, 68Ga-PSMA and 18F-NaF have been investigated to mitigate the limitations of conventional imaging modalities. Diagnostic radiotracers that have properties similar to a therapeutic radiotracer will precisely assess of the possibility and efficacy of a treatment; this is the theranostic concept. An example of a diagnostic test employed for selecting targeted therapy is the combined use of 18F-fluoride PET/CT for evaluation of possible therapy with 223Ra. CONCLUSION: This review examines the most recent publications related to this topic.