Publications by authors named "Jukka Kemppainen"

90 Publications

More Than Meets the Eye: Scientific Rationale behind Molecular Imaging and Therapeutic Targeting of Prostate-Specific Membrane Antigen (PSMA) in Metastatic Prostate Cancer and Beyond.

Cancers (Basel) 2021 May 7;13(9). Epub 2021 May 7.

Institute of Biomedicine, Cancer Research Unit, FICAN West Cancer Center Laboratory, University of Turku and Turku University Hospital, FI-20520 Turku, Finland.

Prostate cancer is the second most common cancer type in men globally. Although the prognosis for localized prostate cancer is good, no curative treatments are available for metastatic disease. Better diagnostic methods could help target therapies and improve the outcome. Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is overexpressed on malignant prostate tumor cells and correlates with the aggressiveness of the disease. PSMA is a clinically validated target for positron emission tomography (PET) imaging-based diagnostics in prostate cancer, and during recent years several therapeutics have been developed based on PSMA expression and activity. The expression of PSMA in prostate cancer can be very heterogeneous and some metastases are negative for PSMA. Determinants that dictate clinical responses to PSMA-targeting therapeutics are not well known. Moreover, it is not clear how to manipulate PSMA expression for therapeutic purposes and develop rational treatment combinations. A deeper understanding of the biology behind the use of PSMA would help the development of theranostics with radiolabeled compounds and other PSMA-based therapeutic approaches. Along with PSMA several other targets have also been evaluated or are currently under investigation in preclinical or clinical settings in prostate cancer. Here we critically elaborate the biology and scientific rationale behind the use of PSMA and other targets in the detection and therapeutic targeting of metastatic prostate cancer.
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http://dx.doi.org/10.3390/cancers13092244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125679PMC
May 2021

Prospective comparison of F-PSMA-1007 PET/CT, whole-body MRI and CT in primary nodal staging of unfavourable intermediate- and high-risk prostate cancer.

Eur J Nucl Med Mol Imaging 2021 Mar 13. Epub 2021 Mar 13.

Department of Urology, University of Turku and Turku University Hospital, Turku, Finland.

Purpose: To prospectively compare F-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography (PET)/CT, whole-body magnetic resonance imaging (WBMRI) including diffusion-weighted imaging (DWI) and standard computed tomography (CT), in primary nodal staging of prostate cancer (PCa).

Methods: Men with newly diagnosed unfavourable intermediate- or high-risk PCa prospectively underwent F-PSMA-1007 PET/CT, WBMRI with DWI and contrast-enhanced CT within a median of 8 days. Six readers (two for each modality) independently reported pelvic lymph nodes as malignant, equivocal or benign while blinded to the other imaging modalities. Sensitivity, specificity and accuracy were reported according to optimistic (equivocal lesions interpreted as benign) and pessimistic (equivocal lesions interpreted as malignant) analyses. The reference standard diagnosis was based on multidisciplinary consensus meetings where available histopathology, clinical and follow-up data were used.

Results: Seventy-nine patients completed all the imaging modalities, except for one case of interrupted WBMRI. Thirty-one (39%) patients had pelvic lymph node metastases, which were detected in 27/31 (87%), 14/31 (45%) and 8/31 (26%) patients by F-PSMA-1007 PET/CT, WBMRI with DWI and CT, respectively (optimistic analysis). In 8/31 (26%) patients, only F-PSMA-1007 PET/CT detected malignant lymph nodes, while the other two imaging modalities were reported as negative. At the patient level, sensitivity and specificity values for F-PSMA-1007 PET/CT, WBMRI with DWI and CT in optimistic analysis were 0.87 (95%CI 0.71-0.95) and 0.98 (95%CI 0.89-1.00), 0.37 (95%CI 0.22-0.55) and 0.98 (95%CI 0.89-1.00) and 0.26 (95%CI 0.14-0.43) and 1.00 (95%CI 0.93-1.00), respectively.

Conclusion: F-PSMA-1007 PET/CT showed significantly greater sensitivity in nodal staging of primary PCa than did WBMRI with DWI or CT, while maintaining high specificity.

Clinical Trial Registration: Clinicaltrials.gov ID: NCT03537391.
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http://dx.doi.org/10.1007/s00259-021-05296-1DOI Listing
March 2021

Functional imaging with 11C-metomidate PET for subtype diagnosis in primary aldosteronism.

Eur J Endocrinol 2020 Dec;183(6):539-550

Endocrinology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Objective: Endocrine Society guidelines recommend adrenal venous sampling (AVS) in primary aldosteronism (PA) if adrenalectomy is considered. We tested whether functional imaging of adrenal cortex with 11C-metomidate (11C-MTO) could offer a noninvasive alternative to AVS in the subtype classification of PA.

Design: We prospectively recruited 58 patients with confirmed PA who were eligible for adrenal surgery.

Methods: Subjects underwent AVS and 11C-MTO-PET without dexamethasone pretreatment in random order. The lateralization of 11C-MTO-PET and adrenal CT were compared with AVS in all subjects and in a prespecified adrenalectomy subgroup in which the diagnosis was confirmed with immunohistochemical staining for CYP11B2.

Results: In the whole study population, the concordance of AVS and 11C-MTO-PET was 51% and did not differ from that of AVS and adrenal CT (53%). The concordance of AVS and 11C-MTO-PET was 55% in unilateral and 44% in bilateral PA. In receiver operating characteristics analysis, the maximum standardized uptake value ratio of 1.16 in 11C-MTO-PET had an AUC of 0.507 (P = n.s.) to predict allocation to adrenalectomy or medical therapy with sensitivity of 55% and specificity of 44%. In the prespecified adrenalectomy subgroup, AVS and 11C-MTO-PET were concordant in 10 of 19 subjects with CYP11B2-positive adenoma and in 6 of 10 with CYP11B2-positivity without an adenoma.

Conclusions: The concordance of 11C-MTO-PET with AVS was clinically suboptimal, and did not outperform adrenal CT. In a subgroup with CYP11B2-positive adenoma, 11C-MTO-PET identified 53% of cases. 11C-MTO-PET appeared to be inferior to AVS for subtype classification of PA.
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http://dx.doi.org/10.1530/EJE-20-0532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045447PMC
December 2020

Exercise training improves adipose tissue metabolism and vasculature regardless of baseline glucose tolerance and sex.

BMJ Open Diabetes Res Care 2020 08;8(1)

Turku PET Centre, University of Turku, Turku, Finland

Introduction: We investigated the effects of a supervised progressive sprint interval training (SIT) and moderate-intensity continuous training (MICT) on adipocyte morphology and adipose tissue metabolism and function; we also tested whether the responses were similar regardless of baseline glucose tolerance and sex.

Research Design And Methods: 26 insulin-resistant (IR) and 28 healthy participants were randomized into 2-week-long SIT (4-6×30 s at maximum effort) and MICT (40-60 min at 60% of maximal aerobic capacity (VO)). Insulin-stimulated glucose uptake and fasting-free fatty acid uptake in visceral adipose tissue (VAT), abdominal and femoral subcutaneous adipose tissues (SATs) were quantified with positron emission tomography. Abdominal SAT biopsies were collected to determine adipocyte morphology, gene expression markers of lipolysis, glucose and lipid metabolism and inflammation.

Results: Training increased glucose uptake in VAT (p<0.001) and femoral SAT (p<0.001) and decreased fatty acid uptake in VAT (p=0.01) irrespective of baseline glucose tolerance and sex. In IR participants, training increased adipose tissue vasculature and decreased CD36 and ANGPTL4 gene expression in abdominal SAT. SIT was superior in increasing VO and VAT glucose uptake in the IR group, whereas MICT reduced VAT fatty acid uptake more than SIT.

Conclusions: Short-term training improves adipose tissue metabolism both in healthy and IR participants independently of the sex. Adipose tissue angiogenesis and gene expression was only significantly affected in IR participants.
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http://dx.doi.org/10.1136/bmjdrc-2019-000830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437884PMC
August 2020

F-FDG positron emission tomography/computed tomography of cardiac implantable electronic device infections.

J Nucl Cardiol 2020 Jul 31. Epub 2020 Jul 31.

Division of Medicine, Turku University Hospital, P.O. Box 52, 20521, Turku, Finland.

Background: The diagnosis of cardiac implantable electronic device (CIED) infection is challenging because of its variable presentations. We studied the value of 2-[F]fluoro-2-deoxy-D-glucose (F-FDG) positron emission tomography/computed tomography (PET/CT) in the detection of CIED infection.

Methods And Results: Thirty patients with suspected CIED infection underwent F-FDG-PET/CT. The control group was ten patients with asymptomatic CIED who underwent cancer-related F-FDG-PET/CT. F-FDG-PET/CT was evaluated visually, semiquantitatively as maximum standardized uptake value (SUV) and target-to-background ratio (TBR). Final diagnosis of CIED infection was based on clinical and bacteriological data. F-FDG-PET/CT was visually positive in all 9 patients with recent (≤ 8 weeks) implantation of CIED, but only 4 had confirmed CIED infection. F-FDG-PET/CT was true positive in 9 out of 21 cases with remote implantation of CIED and false positive in 3 (14.3%) cases. F-FDG-PET/CT was also false positive in 3 (30%) cases of control group. The SUV of the pocket area was significantly higher in patients with CIED infection than in the control group (4.8 ± 2.4 vs 2.0 ± .8, P < .001). By using the cut-off value of TBR ≥ 1.8, sensitivity of F-FDG-PET/CT for the diagnosis of CIED infection in patients with remote implantation was 90% and specificity 73%, PPV 75%, and NPV 89%.

Conclusions: F-FDG-PET/CT is a sensitive but nonspecific method in the diagnosis of CIED infection.
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http://dx.doi.org/10.1007/s12350-020-02256-4DOI Listing
July 2020

The value of combined positron emission tomography/magnetic resonance imaging to diagnose inflammatory bowel disease: a prospective study.

Acta Radiol 2020 Jul 28:284185120944900. Epub 2020 Jul 28.

Department of Medicine, University of Turku, Turku, Finland.

Background: The clinical utility of positron emission tomography/magnetic resonance imaging (PET/MRI) in comparison to standard work-up with patients with known or suspected inflammatory bowel disease (IBD) is unknown.

Purpose: To evaluate the value of 18F-fluorodeoxyglucose (18F-FDG) PET/MRI in the diagnostics of IBD and further compare the data obtained using PET/MRI to histological findings.

Materials And Methods: Ten patients with relapse in IBD or with symptoms of suspected IBD were recruited either from a gastroenterology outpatient clinic or from a hospital ward. Intestinal inflammation was assessed with histology and 18F-FDG PET/MRI. Maximum standard uptake values (SUV) were calculated in six regions of the intestine (small bowel, ascending, transverse, descending and sigmoid colon, and rectum) and compared to histological analysis of inflammation activity.

Results: The study showed that both the inflammation activity ( = 0.008) and the region of the biopsy in the intestine ( = 0.015) had a significant effect on SUV. SUVs obtained from severe inflammation activity emerged significantly from the background ( = 0.006). In addition, the SUVs obtained from moderate inflammation raised from background, but the difference was not statistically significant ( = 0.083), while SUVs of mild inflammation were at the same level with SUVs of normal bowel wall ( = 0.988).

Conclusion: 18F-FDG PET/MRI is a promising method of detecting especially severe inflammatory bowel lesions. More data are required to define its sensitivity and specificity.
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http://dx.doi.org/10.1177/0284185120944900DOI Listing
July 2020

A Prospective Comparison of F-prostate-specific Membrane Antigen-1007 Positron Emission Tomography Computed Tomography, Whole-body 1.5 T Magnetic Resonance Imaging with Diffusion-weighted Imaging, and Single-photon Emission Computed Tomography/Computed Tomography with Traditional Imaging in Primary Distant Metastasis Staging of Prostate Cancer (PROSTAGE).

Eur Urol Oncol 2020 Jul 13. Epub 2020 Jul 13.

Department of Urology, University of Turku and Turku University Hospital, Turku, Finland.

Background: Computed tomography (CT) and bone scintigraphy (BS) are the imaging modalities currently used for distant metastasis staging of prostate cancer (PCa).

Objective: To compare standard staging modalities with newer and potentially more accurate imaging modalities.

Design, Setting, And Participants: This prospective, single-centre trial (NCT03537391) enrolled 80 patients with newly diagnosed high-risk PCa (International Society of Urological Pathology grade group ≥3 and/or prostate-specific antigen [PSA] ≥20 and/or cT ≥ T3; March 2018-June 2019) to undergo primary metastasis staging with two standard and three advanced imaging modalities.

Outcome Measurements And Statistical Analysis: The participants underwent the following five imaging examinations within 2 wk of enrolment and without a prespecified sequence: BS, CT, Tc-hydroxymethylene diphosphonate (Tc-HMDP) single-photon emission computed tomography (SPECT)-CT, 1.5 T whole-body magnetic resonance imaging (WBMRI) using diffusion-weighted imaging, and F-prostate-specific membrane antigen-1007 (F-PSMA-1007) positron emission tomography(PET)-CT. Each modality was reviewed by two independent experts blinded to the results of the prior studies, who classified lesions as benign, equivocal, or malignant. Pessimistic and optimistic analyses were performed to resolve each equivocal diagnosis. The reference standard diagnosis was defined using all available information accrued during at least 12 mo of clinical follow-up. Patients with equivocal reference standard diagnoses underwent MRI and/or CT to search for the development of anatomical correspondence. PSMA PET-avid lesions without histopathological verification were rated to be malignant only if there was a corresponding anatomical finding suspicious for malignancy at the primary or follow-up imaging.

Results And Limitations: Seventy-nine men underwent all imaging modalities except for one case of interrupted MRI. The median interval per patient between the first and the last imaging study was 8 d (interquartile range [IQR]: 6-9). The mean age was 70 yr (standard deviation: 7) and median PSA 12 ng/mL (IQR:7-23). The median follow-up was 435 d (IQR: 378-557). Metastatic disease was detected in 20 (25%) patients. The imaging modality F-PSMA-1007 PET-CT had superior sensitivity and highest inter-reader agreement. The area under the receiver-operating characteristic curve (AUC) values for bone metastasis detection with PSMA PET-CT were 0.90 (95% confidence interval [CI]: 0.85-0.95) and 0.91 (95% CI: 0.87-0.96) for readers 1 and 2, respectively, while the AUC values for BS, CT, SPECT-CT, and WBMRI were 0.71 (95% CI: 0.58-0.84) and 0.8 (95% CI: 0.67-0.92), 0.53 (95% CI: 0.39-0.67) and 0.66 (95% CI: 0.54-0.77), 0.77 (95% CI: 0.65-0.89) and 0.75 (95% CI: 0.62-0.88), and 0.85 (95% CI: 0.74-0.96) and 0.67 (95% CI: 0.54-0.80), respectively, for the other four pairs of readers. The imaging method F-PSMA-1007 PET-CT detected metastatic disease in 11/20 patients in whom standard imaging was negative and influenced clinical decision making in 14/79 (18%) patients. In 12/79 cases, false positive bone disease was reported only by PSMA PET-CT. Limitations included a nonrandomised study setting and few histopathologically validated suspicious lesions.

Conclusions: Despite the risk of false positive bone lesions, F-PSMA-1007 PET-CT outperformed all other imaging methods studied for the detection of primary distant metastasis in high-risk PCa.

Patient Summary: In this report, we compared the diagnostic performance of conventional and advanced imaging. It was found that F-prostate-specific membrane antigen-1007 positron emission tomography/computed tomography (F-PSMA-1007 PET-CT) was superior to the other imaging modalities studied for the detection of distant metastasis at the time of initial diagnosis of high-risk prostate cancer. PSMA PET-CT also appears to detect some nonmetastatic bone lesions.
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http://dx.doi.org/10.1016/j.euo.2020.06.012DOI Listing
July 2020

Prediction of prostate cancer aggressiveness using F-Fluciclovine (FACBC) PET and multisequence multiparametric MRI.

Sci Rep 2020 06 10;10(1):9407. Epub 2020 Jun 10.

Department of Diagnostic Radiology, University of Turku, Turku, Finland.

The aim of this prospective single-institution clinical trial (NCT02002455) was to evaluate the potential of advanced post-processing methods for F-Fluciclovine PET and multisequence multiparametric MRI in the prediction of prostate cancer (PCa) aggressiveness, defined by Gleason Grade Group (GGG). 21 patients with PCa underwent PET/CT, PET/MRI and MRI before prostatectomy. DWI was post-processed using kurtosis (ADC, K), mono- (ADC), and biexponential functions (f, D, D) while Logan plots were used to calculate volume of distribution (V). In total, 16 unique PET (V, SUV) and MRI derived quantitative parameters were evaluated. Univariate and multivariate analysis were carried out to estimate the potential of the quantitative parameters and their combinations to predict GGG 1 vs >1, using logistic regression with a nested leave-pair out cross validation (LPOCV) scheme and recursive feature elimination technique applied for feature selection. The second order rotating frame imaging (RAFF), monoexponential and kurtosis derived parameters had LPOCV AUC in the range of 0.72 to 0.92 while the corresponding value for V was 0.85. he best performance for GGG prediction was achieved by K parameter of kurtosis function followed by quantitative parameters based on DWI, RAFF and F-FACBC PET. No major improvement was achieved using parameter combinations with or without feature selection. Addition of F-FACBC PET derived parameters (V, SUV) to DWI and RAFF derived parameters did not improve LPOCV AUC.
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http://dx.doi.org/10.1038/s41598-020-66255-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287051PMC
June 2020

Changes in quadriceps femoris muscle perfusion following different degrees of cold-water immersion.

J Appl Physiol (1985) 2020 05 30;128(5):1392-1401. Epub 2020 Apr 30.

Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom.

We examined the influence of graded cold-water immersion (CWI) on global and regional quadriceps muscle perfusion with positron emission tomography (PET) and [O]HO. In 30 healthy men [33 ± 8 yr; 81 ± 10 kg; 184 ± 5 cm; percentage body fat: 13 ± 5%; peak oxygen uptake (V̇o): 47 ± 8 mL·kg·min] quadriceps perfusion, thigh and calf cutaneous vascular conductance (CVC), intestinal, muscle, and local skin temperatures, thermal comfort, mean arterial pressure, and heart rate were assessed before and after 10 min of CWI at 8°C, 15°C, or 22°C. Global quadriceps perfusion did not change beyond a clinically relevant threshold (0.75 mL·100 g·min) in any condition and was similar between conditions {range of differences [95% confidence interval (CI)]: 0.1 mL·100 g·min (-0.9 to 1.2 mL·100 g·min) to 0.9 mL·100 g·min (-0.2 to 1.9 mL·100 g·min)}. Muscle perfusion was greater in vastus intermedius (VI) compared with vastus lateralis (VL) (2.2 mL·100 g·min; 95% CI 1.5 to 3.0 mL·100 g·min) and rectus femoris (RF) (2.2 mL·100 g·min; 1.4 to 2.9 mL·100 g·min). A clinically relevant increase in VI muscle perfusion after immersion at 8°C and a decrease in RF muscle perfusion at 15°C were observed. A clinically relevant increase in perfusion was observed in VI in 8°C compared with 22°C water (2.3 mL·100 g·min; 1.1 to 3.5 mL·100 g·min). There were no clinically relevant between-condition differences in thigh CVC. Our findings suggest that CWI (8-22°C) does not reduce global quadriceps muscle perfusion to a clinically relevant extent; however, colder water increases (8°C) deep muscle perfusion and reduces (15°C) superficial muscle (RF) perfusion in the quadriceps muscle. Using positron emission tomography, we report for the first time muscle perfusion heterogeneity in the quadriceps femoris in response to different degrees of cold-water immersion (CWI). Noxious CWI temperatures (8°C) increase perfusion in the deep quadriceps muscle, whereas superficial quadriceps muscle perfusion is reduced in cooler (15°C) water. Therefore, these data have important implications for the selection of CWI approaches used in the treatment of soft tissue injury, while also increasing our understanding of the potential mechanisms underpinning CWI.
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http://dx.doi.org/10.1152/japplphysiol.00833.2019DOI Listing
May 2020

Prospective study on the effect of short-term androgen deprivation therapy on PSMA uptake evaluated with Ga-PSMA-11 PET/MRI in men with treatment-naïve prostate cancer.

Eur J Nucl Med Mol Imaging 2020 03 26;47(3):665-673. Epub 2019 Dec 26.

Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, Turku, Finland.

Purpose: Based on in vitro studies, it is known that androgen deprivation therapy (ADT) increases prostate-specific membrane antigen (PSMA) expression. Therefore, we hypothesised that ADT improves the performance of PSMA-PET imaging in primary staging of prostate cancer. The purpose of the study was to demonstrate the time course effect of ADT on PSMA uptake in different types of metastatic lesions evaluated with Ga-PSMA-11 PET/MRI.

Methods: Nine men with treatment-naïve prostate cancer were enrolled to a prospective, registered (NCT03313726) clinical trial. A Ga-PSMA-11 PET/MRI was performed once before and 3 times post-ADT (degarelix, Firmagon). Change of maximum standardised uptake values (SUVmax) in prostate, lymph nodes, bone metastases, and physiologically PSMA-avid organs were evaluated in a time frame of 1-8 weeks.

Results: All patients reached castration levels within 10 days, and 50% decrease in prostate-specific antigen (PSA) concentration was observed 14 days post-ADT. A heterogeneous increase in PSMA uptake was observed 3 to 4 weeks post-ADT. This phenomenon was definitively more evident in bone metastases: 13 (57%) of the metastasis, with a mean (range) SUVmax increase of 77% (8-238%). In one patient, already having bone metastases at baseline, three new bone metastases were observed post-ADT. Of lesions with reduced SUVmax, none disappeared.

Conclusions: Both in patient and region level, increase in PSMA uptake post-ADT is heterogenous and is seen most evidently in bone metastases. Preliminary results on a small cohort of patients suggest the clinical impact of ADT on improving the performance of Ga-PSMA PET in staging seems to be minor. However, the optimal imaging time point might be 3 to 4 weeks post-ADT. Since none of the metastases with decreasing SUVmax disappeared, it seems that short-term usage of ADT does not interfere with the interpretation of Ga-PSMA PET.

Trial Registration: NCT03313726, registered 18 October 2017; EUDRA-CT, 2017-002345-29.
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http://dx.doi.org/10.1007/s00259-019-04635-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081750PMC
March 2020

Prediction of the aggressiveness of non-functional pancreatic neuroendocrine tumors based on the dual-tracer PET/CT.

EJNMMI Res 2019 Dec 23;9(1):116. Epub 2019 Dec 23.

Division of Digestive Surgery and Urology, Turku University Hospital, P.O. Box 52, FIN-20521, Turku, Finland.

Background: Predicting the aggressive behavior of non-functional pancreatic neuroendocrine tumors (NF-PNET) remains controversial. We wanted to explore, in a prospective setting, whether the diagnostic accuracy can be improved by dual-tracer functional imaging Ga-DOTANOC and F-FDG-PET/CT in patients with NF-PNETs.

Methods: Thirty-one patients with NF-PNET (90% asymptomatic) underwent PET-imaging with F-FDG and Ga-DOTANOC, followed by surgery (n = 20), an endoscopic ultrasonography and fine-needle biopsy (n = 2) or follow-up (n = 9). A focal activity on PET/CT greater than the background that could not be identified as physiological activity was considered to indicate tumor tissue. The imaging results were compared to histopathology. The mean follow-up time was 31.3 months.

Results: Thirty-one patients presented a total of 53 lesions (40 histologically confirmed) on PET/CT. Thirty patients had a Ga-DOTANOC-positive tumor (sensitivity 97%) and 10 patients had an F-FDG-positive tumor. In addition, one Ga-DOTANOC-negative patient was F-FDG-positive. F-FDG-PET/CT was positive in 19% (3/16) of the G1 tumors, 63% (5/8) of the G2 tumors and 1/1 of the well-differentiated G3 tumor. Ga-DOTANOC-PET/CT was positive in 94% of the G1 tumors, 100% of the G2 tumors and 1/1 of the well-differentiated G3 tumor. Two out of six (33%) of the patients with lymph node metastases (LN+) were F-FDG-positive. The F-FDG-PET/CT correlated with tumor Ki-67 (P = 0.021). Further, the Krenning score correlated with tumor Ki-67 (P = 0.013). F-FDG-positive tumors were significantly larger than the F-FDG-negative tumors (P = 0.012). F-FDG-PET/CT showed a positive predictive value of 78% in the detection of potentially aggressive tumors (G2, G3, or LN + PNETs); the negative predictive value was 69%.

Conclusions: F-FDG-PET/CT is useful to predict tumor grade but not the LN+ of NF-PNETs. Patients with F-FDG-avid NF-PNETs should be referred for surgery. The Ga-DOTANOC-PET/CT also has prognostic value since the Krenning score predicts the histopathological tumor grade.

Trial Registration: The study has been registered at ClinicalTrials.gov; Non-functional Pancreatic NET and PET imaging, NCT02621541.
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http://dx.doi.org/10.1186/s13550-019-0585-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928175PMC
December 2019

PET/CT for Evaluation of Ovarian Cancer.

Semin Nucl Med 2019 11 4;49(6):484-492. Epub 2019 Jul 4.

Turku PET Centre, University of Turku, Turku, Finland; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku Finland.

Ovarian cancer is the leading cause of death from gynecologic cancer in the developed countries. It is usually diagnosed in advanced stage since it is often symptomless or symptoms are nonspecific in early course of the disease. It has a high recurrence rate and poor prognosis in advanced disease. Ovarian cancer has distinct type of disease spread in abdomen and above diaphragm. Surgery is irreplaceable in staging but multimodality imaging approach is often needed during the diagnosis, treatment monitoring, and follow-up of patients with ovarian cancer, typically ultrasound, CT, MRI and PET/CT are the main modalities used. The current clinical role of PET/CT in evaluation of ovarian cancer during staging, treatment prognostication and response assessment, and in disease recurrence is discussed in this review compared to conventional imaging.
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http://dx.doi.org/10.1053/j.semnuclmed.2019.06.010DOI Listing
November 2019

The Clinical Impact of Using F-FDG-PET/CT in the Diagnosis of Suspected Vasculitis: The Effect of Dose and Timing of Glucocorticoid Treatment.

Contrast Media Mol Imaging 2019 29;2019:9157637. Epub 2019 Aug 29.

Department of Medicine, University of Turku, Turku, Finland.

F-Fluorodeoxyglucose positron-emission tomography (F-FDG-PET) with computed tomography (CT) is effective for diagnosing large vessel vasculitis, but its usefulness in accurately diagnosing suspected, unselected vasculitis remains unknown. We evaluated the feasibility of F-FDG-PET/CT in real-life cohort of patients with suspicion of vasculitis. The effect of the dose and the timing of glucocorticoid (GC) medication on imaging findings were in special interest. 82 patients with suspected vasculitis were evaluated by whole-body F-FDG-PET/CT. GC treatment as prednisolone equivalent doses at the scanning moment and before imaging was evaluated. 38/82 patients were diagnosed with vasculitis. Twenty-one out of 38 patients had increased F-FDG accumulation in blood vessel walls indicating vasculitis in various sized vessels. Vasculitis patients with a positive vasculitis finding in F-FDG-PET/CT had a significantly shorter duration of GC use (median = 4.0 vs 7.0 days, =0.034), and they used lower GC dose during the PET scan (median dose = 15.0 mg/day vs 40.0 mg/day, =0.004) compared to F-FDG-PET/CT-negative patients. Vasculitis patients with a positive F-FDG-PET/CT result had significantly higher C-reactive protein (CRP) than patients with a negative F-FDG-PET/CT finding (mean value = 154.5 vs 90.4 mg/L, =0.018). We found that F-FDG-PET/CT positivity was significantly associated with a lower dose and shorter duration of GC medication and higher CRP level in vasculitis patients. F-FDG-PET/CT revealed clinically significant information in over half of the patients and was effective in confirming the final diagnosis.
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http://dx.doi.org/10.1155/2019/9157637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735179PMC
July 2020

Myocardial Blood Flow and Metabolic Rate of Oxygen Measurement in the Right and Left Ventricles at Rest and During Exercise Using O-Labeled Compounds and PET.

Front Physiol 2019 19;10:741. Epub 2019 Jun 19.

Turku PET Centre, University of Turku, Turku, Finland.

Simultaneous measurement of right (RV) and left ventricle (LV) myocardial blood flow (MBF), oxygen extraction fraction (OEF), and oxygen consumption (MVO) non-invasively in humans would provide new possibilities to understand cardiac physiology and different patho-physiological states. We developed and tested an optimized novel method to measure MBF, OEF, and MVO simultaneously both in the RV and LV free wall (FW) using positron emission tomography in healthy young men at rest and during supine bicycle exercise. Resting MBF was not significantly different between the three myocardial regions. Exercise increased MBF in the LVFW and septum, but MBF was lower in the RV compared to septum and LVFW during exercise. Resting OEF was similar between the three different myocardial regions (~70%) and increased in response to exercise similarly in all regions. MVO increased approximately two to three times from rest to exercise in all myocardial regions, but was significantly lower in the RV during exercise as compared to septum LVFW. MBF, OEF, and MVO can be assessed simultaneously in the RV and LV myocardia at rest and during exercise. Although there are no major differences in the MBF and OEF between LV and RV myocardial regions in the resting myocardium, MVO per gram of myocardium appears to be lower the RV in the exercising healthy human heart due to lower mean blood flow. The presented method may provide valuable insights for the assessment of MBF, OEF and MVO in hearts in different pathophysiological states.
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http://dx.doi.org/10.3389/fphys.2019.00741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593089PMC
June 2019

Correlation between F-1-amino-3-fluorocyclobutane-1-carboxylic acid (F-fluciclovine) uptake and expression of alanine-serine-cysteine-transporter 2 (ASCT2) and L-type amino acid transporter 1 (LAT1) in primary prostate cancer.

EJNMMI Res 2019 May 31;9(1):50. Epub 2019 May 31.

Turku PET Centre, Turku, Finland.

Purpose: To evaluate the expression of alanine-serine-cysteine-transporter 2 (ASCT2) and L-type amino acid transporter1 (LAT1) in prostate cancer (PCa) and their impact on uptake of F-1-amino-3-fluorocyclobutane-1-carboxylic acid (F-fluciclovine) which is approved for the detection of recurrent PCa.

Methods: Twenty-five hormone-naïve patients with histologically confirmed PCa underwent PET/CT before prostatectomy. Dynamic imaging was performed immediately after injection of 368 ± 10 MBq of F-fluciclovine and the uptake in PCa was expressed as SUV at six sequential 4-min time frames and as tracer distribution volume (V) using Logan plots over 0-24 min. The expression of ASCT2 and LAT1 was studied with immunohistochemistry (IHC) on a tissue microarray (TMA) containing three cores per carcinoma lesion. The TMA slides were scored independently by two trained readers based on visual intensity of ASCT2/LAT1 expression on a four-tiered scale. The correlations between ASCT2/LAT1 staining intensity, SUVmax/V, and Gleason grade group (GGG) were assessed using Spearman's rank correlation coefficient (ρ).

Results: Forty tumor foci (> 0.5 mm in diameter, max. 3 per patient) were available for TMA. In visual scoring, low, moderate, and high staining intensity of ASCT2 was observed in 4 (10%), 24 (60%), and 12 (30%) tumors, respectively. No tumors showed high LAT1 staining intensity while moderate intensity was found in 10 (25%), 25 (63%) showed low, and the remaining 5 (12%) were negative for staining with LAT1. Tumors with GGG > 2 showed significantly higher uptake of F-fluciclovine and higher LAT1 staining intensity (p < 0.05). The uptake of F-fluciclovine correlated significantly with LAT1 expression (ρ = 0.39, p = 0.01, for SUV at 2 min and ρ = 0.39, p = 0.01 for V). No correlation between ASCT2 expression and F-fluciclovine uptake or GGG was found.

Conclusions: Our findings suggest that LAT1 is moderately associated with the transport of F-fluciclovine in local PCa not exposed to hormonal therapy. Both high and low Gleason grade tumors express ASCT2 while LAT1 expression is less conspicuous and may be absent in some low-grade tumors. Our observations may be of importance when using F-fluciclovine imaging in the planning of focal therapies for PCa.
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http://dx.doi.org/10.1186/s13550-019-0518-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544711PMC
May 2019

Behavior of FDG-avid supradiaphragmatic lymph nodes in PET/CT throughout primary therapy in advanced serous epithelial ovarian cancer: a prospective study.

Cancer Imaging 2019 May 29;19(1):27. Epub 2019 May 29.

Department of Obstetrics and Gynecology, Turku University Hospital, University of Turku, Kiinamyllynkatu 4-8, 20521, Turku, Finland.

Background: Epithelial ovarian cancer (EOC) typically spreads intra-abdominally, but preoperative evaluation with FDG PET/CT often reveals metabolically active supradiaphragmatic lymph nodes (sdLNs). Their clinical significance and behavior during treatment has not been established.

Methods: EOC patients with PET positive sdLNs at diagnosis were prospectively followed with PET/CT after primary chemotherapy and at the first recurrence. In each patient, 2 most active LNs in 5 different supradiaphramatic regions were evaluated and the size and changes in FDG uptake (SUVmax) were recorded. The patients´ overall response to primary treatment was defined with RECIST criteria. The behavior of sdLNs during chemotherapy were compared in treatment responders and non-responders. Recurrence patterns were monitored.

Results: Forty-one patients with 127 PET/CT scans were systematically evaluated. In pretreatment scan, 76% (31/41) of patients had FDG-avid sdLNs in multiple anatomical sites. Only a minority (22/136) of the sdLNs were enlarged in size, but their histopathologic confirmation by biopsy was not possible. Only 6/41 patients had FDG-avid sdLNs in a single surgically approachable site. The sdLNs became inactive during primary chemotherapy more often in the RECIST responders compared to the non-responders (HR 1.46 (95%CI: 1.09-1.96), p = 0.002). The size and SUVmax values did not predict treatment outcome. In 50% of the responders the same sdLNs reactivated when recurrence occurred. Persistent post-treatment metabolic activity did not predict earlier disease relapse (p = 0.59).

Conclusion: The behavior of metabolically active sdLNs during chemotherapy supports their metastatic nature. Due to their distribution to multiple regions, the benefit of removal of reachable sdLNS seems unlikely.

Trial Registration: NCT, NCT01276574 . Registered 1 September 2010.
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http://dx.doi.org/10.1186/s40644-019-0215-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542004PMC
May 2019

Perioperative EOX treatment in operable locally advanced gastroesophageal adenocarcinoma: Prediction of tumor response by FDG -PET and histopathology.

Surg Oncol 2019 Mar 7;28:42-49. Epub 2018 Nov 7.

Turku University Hospital, Department of Digestive Surgery, Finland.

Purpose: The aim of this retrospective single-center analysis was to evaluate the feasibility of fluorine-18 fluorodeoxyglucose (FDG)-PET imaging in evaluating metabolic response of preoperative chemotherapy in the treatment of locally advanced operable gastroesophageal adenocarcinoma and to investigate the association between histopathologic and FDG-PET response and overall survival.

Methods: Patients with locally advanced adenocarcinoma of distal esophagus, gastroesophageal junction or stomach were assessed for the study during 2008-2012. After evaluation with endoscopy, computed tomography and FDG-PET, patients with clinical stage II or III disease were assigned for perioperative EOX (epirubicin-oxaliplatin-capecitabine) treatment targeted at three cycles both pre- and postoperatively, if possible. Metabolic response was evaluated by repeated FDG-PET during or right after the second chemotherapy cycle. Becker tumor regression grade (TRG) was used to evaluate histopathologic response. For statistical purposes, the clinically significant cut-off for tumor maximum standardized uptake value (SUV) change (SUVδ%) was set at -35%.

Results: 54 patients were included in the study. 53 PET images were obtained before chemotherapy, 11 (21%) of those were PET negative. A major metabolic response was detected in 19 patients and major histopathologic response in 14 patients. No statistically significant association was observed between SUVδ% and histopathological responses. Median overall survival (OS) time of the patients was 49.9 months. No association between OS and PET response was found in our study. The administration of all six cycles of perioperative EOX was associated with improved OS.

Conclusions: Follow-up PET during or right after second preoperative chemotherapy cycle did not assist in identifying patients with favorable histopathological response or OS.
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http://dx.doi.org/10.1016/j.suronc.2018.11.002DOI Listing
March 2019

Comparison of standardized uptake values between Tc-HDP SPECT/CT and F-NaF PET/CT in bone metastases of breast and prostate cancer.

EJNMMI Res 2019 Jan 24;9(1). Epub 2019 Jan 24.

Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Kiinamyllynkatu 4-8, 20521, Turku, Finland.

Background: Despite recent technological advances allowing for quantitative single-photon emission computed tomography (SPECT), quantitative SPECT has not been widely used in the clinical practice. The aim of this study is to evaluate the feasibility of quantitative SPECT for measuring metastatic bone uptake in breast and prostate cancer by comparing standard uptake values (SUVs) measured with Tc-HDP SPECT/CT and F-NaF PET/CT.

Methods: Twenty-six breast and 27 prostate cancer patients at high risk of bone metastases underwent both Tc-HDP SPECT/CT and F-NaF PET/CT within 14 days of each other. The SPECT and PET data were reconstructed using ordered-subset expectation-maximization algorithms achieving quantitative images. Metastatic and benign skeletal lesions visible in both data sets were identified, and their maximum, peak, and mean SUVs (SUV, SUV, and SUV) were determined. SUV ratios (SUVRs) between the lesions and adjacent normal appearing bone were also calculated. Linear regression was used to evaluate the correlations between the SUVs of SPECT and PET and Bland-Altman plots to evaluate the differences between the SUVs and SUVRs of SPECT and PET.

Results: A total of 231 skeletal lesions, 129 metastatic and 102 benign, were analyzed. All three SUV measures correlated very strongly between SPECT and PET (R ≥ 0.80, p < 0.001) when all lesions were included, and the PET SUVs were significantly higher than SPECT SUVs (p < 0.001). The median differences were 21%, 12%, and 19% for SUV, SUV, and SUV, respectively. On the other hand, the SUVRs were similar between SPECT and PET with median differences of 2%, - 9%, and 2% for SUVR, SUVR, and SUVR, respectively.

Conclusion: The strong correlation between SUVs and similar SUVRs of Tc-HDP SPECT/CT and F-NaF PET/CT demonstrate that SPECT is an applicable tool for clinical quantification of bone metabolism in osseous metastases in breast and prostate cancer patients.
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http://dx.doi.org/10.1186/s13550-019-0475-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346696PMC
January 2019

Muscle Free Fatty-Acid Uptake Associates to Mechanical Efficiency During Exercise in Humans.

Front Physiol 2018 21;9:1171. Epub 2018 Aug 21.

Turku PET Centre, University of Turku, Turku, Finland.

Intrinsic factors related to muscle metabolism may explain the differences in mechanical efficiency (ME) during exercise. Therefore, this study aimed to investigate the relationship between muscle metabolism and ME. Totally 17 healthy recreationally active male participants were recruited and divided into efficient (EF; = 8) and inefficient (IE; = 9) groups, which were matched for age (mean ± SD 24 ± 2 vs. 23 ± 2 years), BMI (23 ± 1 vs. 23 ± 2 kg m), physical activity levels (3.4 ± 1.0 vs. 4.1 ± 1.0 sessions/week), and Opeak (53 ± 3 vs. 52 ± 3 mL kg min), respectively, but differed for ME at 45% of Opeak intensity during submaximal bicycle ergometer test (EF 20.5 ± 3.5 vs. IE 15.4 ± 0.8%, < 0.001). Using positron emission tomography, muscle blood flow (BF) and uptakes of oxygen (m O), fatty acids (FAU) and glucose (GU) were measured during dynamic submaximal knee-extension exercise. Workload-normalized BF (EF 35 ± 14 vs. IE 34 ± 11 mL 100 g min, = 0.896), m O (EF 4.1 ± 1.2 vs. IE 3.9 ± 1.2 mL 100 g min, = 0.808), and GU (EF 3.1 ± 1.8 vs. IE 2.6 ± 2.3 μmol 100 g min, = 0.641) as well as the delivery of oxygen, glucose, and FAU, as well as respiratory quotient were not different between the groups. However, FAU was significantly higher in EF than IE (3.1 ± 1.7 vs. 1.7 ± 0.6 μmol 100 g min, = 0.047) and it also correlated with ME ( = 0.56, = 0.024) in the entire study group. EF group also demonstrated higher use of plasma FAU than IE, but no differences in use of plasma glucose and intramuscular energy sources were observed between the groups. These findings suggest that the effective use of plasma FAU is an important determinant of ME during exercise.
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http://dx.doi.org/10.3389/fphys.2018.01171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6110921PMC
August 2018

Increase of Glucose Uptake in Human Bone Marrow With Increasing Exercise Intensity.

Int J Sport Nutr Exerc Metab 2019 May 18;29(3):254-258. Epub 2018 Nov 18.

1 University of Turku.

Human bone marrow is a metabolically active tissue that responds to acute low-intensity exercise by having increased glucose uptake (GU). Here, the authors studied whether bone marrow GU increases more with increased exercise intensities. Femoral bone marrow GU was measured using positron emission tomography and [F]-fluorodeoxyglucose in six healthy young men during cycling at intensities of 30% (low), 55% (moderate), and 75% (high) of maximal oxygen consumption on three separate days. Bone marrow GU at low was 17.2 µmol·kg·min (range 9.0-25.4) and increased significantly ( = .003) at moderate (31.2 µmol·kg·min, 22.9-39.4) but was not significant from moderate to high (37.4 µmol·kg·min, 29.0-45.7,  = .26). Furthermore, the ratio between bone and muscle GU decreased from low to moderate exercise intensity ( < .01) but not ( = .99) from moderate to high exercise intensity. In conclusion, these results show that although the increase is not as large as observed in exercising skeletal muscle, GU in femoral bone marrow increases with increasing exercise intensity at least from low- to moderate-intensity effort, which may be important for bone and whole-body metabolic health.
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http://dx.doi.org/10.1123/ijsnem.2018-0094DOI Listing
May 2019

Ga-PSMA-PET: added value and future applications in comparison to the current use of choline-PET and mpMRI in the workup of prostate cancer.

Radiol Med 2018 Dec 16;123(12):952-965. Epub 2018 Aug 16.

Nuclear Medicine Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

Positron emission tomography (PET) has been commonly and successfully used, in combination with computed tomography (CT) and more recently magnetic resonance (MRI), in the workup of intermediate or high-risk prostate cancer (PCa). Nowadays, new specific receptor targeted PET tracers in prostate cancer imaging have been introduced; one of the most used is Ga-PSMA, that evaluates the expression of prostate-specific membrane antigen (PSMA). This tracer has been rapidly taken into account for its better sensitivity and specificity compared to lipid metabolism tracers, such as C/F labelled fluorocholine. Besides, in the era of theranostics, this tracer is having a useful application not only for imaging but also for therapeutic purposes. The aim of this review article is, in the first part, to give an overview of the main indications and future development of Ga-PSMA imaging, using PET/CT or PET/MRI, according to the clinical course of the disease and in view of the current use of multiparametric MRI (mpMRI) and choline PET in the management of PCa. In the second part, a brief overview of the promising F-labelled PSMA tracers and the current use of PSMA radionuclide therapy will be provided.
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http://dx.doi.org/10.1007/s11547-018-0929-9DOI Listing
December 2018

C-acetate PET/MRI in bladder cancer staging and treatment response evaluation to neoadjuvant chemotherapy: a prospective multicenter study (ACEBIB trial).

Cancer Imaging 2018 Aug 2;18(1):25. Epub 2018 Aug 2.

Department of Urology, University of Turku and Turku University hospital, Kiinamyllynkatu 4-8, 20520, Turku, Finland.

Background: To evaluate the accuracy of C-acetate Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) in bladder cancer (BC) staging and monitoring response to neoadjuvant chemotherapy (NAC).

Methods: Eighteen patients were prospectively enrolled. Fifteen treatment naive patients underwent C-acetate PET/MRI before transurethral resection of bladder tumor (TUR-BT) for primary tumor evaluation. Five patients with muscle invasive BC were imaged after NAC and prior to radical cystectomy (RC) with extended pelvic lymph node dissection (ePLND) for NAC treatment response evaluation. Two patients were part of both cohorts. C-acetate PET/MRI findings were correlated with histopathology. Accuracy for lymph node detection was evaluated on patient and the ePLND template (10 regions) levels.

Results: The sensitivity, specificity and accuracy of C-acetate PET/MRI for the detection of muscle invasive BC was 1.00, 0.69 and 0.73 while the area under the receiver operating characteristic curve (95% confidence interval) was 0.85 (0.55-1.0), respectively. All five NAC patients underwent chemotherapy as planned and C-acetate PET/MRI correctly staged three patients, overstaged one and understaged one patient compared with RC and ePLND findings. A total of 175 lymph node were removed, median of 35 (range, 27-43) per patient in five patients who had RC and ePLND while 12 (7%) harboured metastases. Sensitivity, specificity, accuracy and AUC for N-staging were 0.20, 0.96, 0.80 and 0.58 on the ePLND template (10 regions) level.

Conclusions: C-acetate PET/MRI is feasible for staging of BC although sensitivity for the detection of nodal metastases is low. Monitoring response to NAC shows promise and warrants evaluation in larger studies.

Trial Registration: ClinicalTrials.gov Identifier: NCT01918592 , registered August 8 2013.
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http://dx.doi.org/10.1186/s40644-018-0158-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090957PMC
August 2018

Mathematical Modeling Predicts Response to Chemotherapy and Drug Combinations in Ovarian Cancer.

Cancer Res 2018 07 16;78(14):4036-4044. Epub 2018 May 16.

Genome-Scale Biology Research Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Platinum-based chemotherapy constitutes the backbone of clinical care in advanced solid cancers such as high-grade serous ovarian cancer (HGSOC) and has prolonged survival of millions of patients with cancer. Most of these patients, however, become resistant to chemotherapy, which generally leads to a fatal refractory disease. We present a comprehensive stochastic mathematical model and simulator approach to describe platinum resistance and standard-of-care (SOC) therapy in HGSOC. We used pre- and posttreatment clinical data, including F-FDG-PET/CT images, to reliably estimate the model parameters and simulate "virtual patients with HGSOC." Treatment responses of the virtual patients generated by our mathematical model were indistinguishable from real-life patients with HGSOC. We demonstrated the utility of our approach by evaluating the survival benefit of combination therapies that contain up to six drugs targeting platinum resistance mechanisms. Several resistance mechanisms were already active at diagnosis, but combining SOC with a drug that targets the most dominant resistance subpopulation resulted in a significant survival benefit. This work provides a theoretical basis for a cancer treatment paradigm in which maximizing platinum's killing effect on cancer cells requires overcoming resistance mechanisms with targeted drugs. This freely available mathematical model and simulation framework enable rapid and rigorous evaluation of the benefit of a targeted drug or combination therapy in virtual patients before clinical trials, which facilitates translating preclinical findings into clinical practice. These findings present a comprehensive mathematical model for platinum resistance and standard-of-care therapy in a solid cancer, allowing virtual evaluation of novel therapy regimens. .
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http://dx.doi.org/10.1158/0008-5472.CAN-17-3746DOI Listing
July 2018

Capnocytophaga canimorsus: a rare case of conservatively treated prosthetic valve endocarditis.

APMIS 2018 May;126(5):453-456

Division of Medicine, Turku University Hospital, Turku, Finland.

We describe a rare case of prosthetic valve endocarditis caused by the canine bacterium Capnocytophaga canimorsus in a male aged 73 years. The diagnosis of infective endocarditis was unequivocal, as it blood cultures were positive for C. canimorsus and vegetations were detected on transesophageal echocardiography; the modified Duke criteria were fulfilled. PET-CT showed intense F-FDG uptake of the prosthetic valve area. The patient was treated with antibiotics alone (no surgery), and is now on life-long suppressive antibiotic therapy. To our knowledge, this is the third reported case of prosthetic valve endocarditis caused by C. canimorsus and the first one to have been treated conservatively.
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http://dx.doi.org/10.1111/apm.12839DOI Listing
May 2018

F-FDG-PET/CT based total metabolic tumor volume change during neoadjuvant chemotherapy predicts outcome in advanced epithelial ovarian cancer.

Eur J Nucl Med Mol Imaging 2018 07 23;45(7):1224-1232. Epub 2018 Feb 23.

Department of Clinical Physiology and Nuclear Medicine, Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland.

Objective: To evaluate the predictive potential of total metabolic tumor volume (MTV) reduction during neoadjuvant chemotherapy (NACT) with F-FDG-PET/CT in an advanced FIGO stage III/IV epithelial ovarian cancer (EOC) patient cohort.

Methods: Twenty-nine primarily inoperable EOC patients underwent F-FDG-PET/CT before and after NACT. The pre- and post-NACT total MTV, in addition to the percentage MTV reduction during NACT, were compared with primary therapy outcome and progression-free survival (PFS). ROC-analysis determined an optimal threshold for MTV reduction identifying patients with progressive or stable disease (PD/SD) at the end of primary therapy. A multivariate analysis with residual tumor (0/>0), FIGO stage (III/IV) and MTV reduction compared to PFS was performed. The association between MTV reduction and overall survival (OS) was evaluated.

Results: The median pre- and post-NACT total MTV were 352 cm (range 150 to 1322 cm) and 51 cm (range 0 to 417 cm), respectively. The median MTV reduction during NACT was 89% (range 24% to 100%). Post-NACT MTV and MTV reduction associated with primary therapy outcome (MTV post-NACT p = 0.007, MTV reduction p = 0.001) and PFS (MTV post-NACT p = 0.005, MTV reduction p = 0.005). MTV reduction <85% identified the PD/SD patients (sensitivity 70%, specificity 78%, AUC 0.79). In a multivariate analysis, MTV reduction (p = 0.002) and FIGO stage (p = 0.003) were statistically significant variables associated with PFS. MTV reduction during NACT corresponded to OS (p = 0.05).

Conclusion: F-FDG-PET/CT is helpful in NACT response evaluation. Patients with total MTV reduction <85% during NACT might be candidates for second-line chemotherapy and clinical trials, instead of interval debulking surgery.
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http://dx.doi.org/10.1007/s00259-018-3961-zDOI Listing
July 2018

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

Eur J Nucl Med Mol Imaging 2018 03 16;45(3):355-364. Epub 2017 Nov 16.

Turku PET Centre, Turku, Finland.

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

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

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

Conclusions: Quantitative F-FACBC imaging significantly correlated with GS but failed to outperform MRI in lesion detection. F-FACBC may assist in targeted biopsies in the setting of hybrid imaging with MRI.
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http://dx.doi.org/10.1007/s00259-017-3875-1DOI Listing
March 2018

Head-to-Head Comparison of Ga-Citrate and F-FDG PET/CT for Detection of Infectious Foci in Patients with Bacteraemia.

Contrast Media Mol Imaging 2017 17;2017:3179607. Epub 2017 Oct 17.

Turku PET Centre, University of Turku, Turku, Finland.

Purpose: This study evaluated the potential of Ga-citrate positron emission tomography/computed tomography (PET/CT) for the detection of infectious foci in patients with bacteraemia by comparing it with 2-[F]fluoro-2-deoxy--glucose (F-FDG) PET/CT.

Methods: Four patients admitted to hospital due to bacteraemia underwent both F-FDG and Ga-citrate whole-body PET/CT scans to detect infectious foci.

Results: The time from hospital admission and the initiation of antibiotic treatment to the first PET/CT was 4-10 days. The time interval between F-FDG and Ga-citrate PET/CT was 1-4 days. Three patients had vertebral osteomyelitis (spondylodiscitis) and one had osteomyelitis in the toe; these were detected by both F-FDG (maximum standardised uptake value [SUV] 6.0 ± 1.0) and Ga-citrate (SUV  6.8 ± 3.5, = 0.61). Three patients had soft tissue infectious foci, with more intense F-FDG uptake (SUV  6.5 ± 2.5) than Ga-citrate uptake (SUV  3.9 ± 1.2, = 0.0033).

Conclusions: Our small cohort of patients with bacteraemia revealed that Ga-citrate PET/CT is comparable to F-FDG PET/CT for detection of osteomyelitis, whereas F-FDG resulted in a higher signal for the detection of soft tissue infectious foci.
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http://dx.doi.org/10.1155/2017/3179607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664237PMC
July 2018

Somatostatin receptor expression in lymphomas: a source of false diagnosis of neuroendocrine tumor at Ga-DOTANOC PET/CT imaging.

Acta Oncol 2018 Feb 7;57(2):283-289. Epub 2017 Jul 7.

b Turku PET Centre, Turku University Hospital, University of Turku , Turku , Finland.

Background: Ga-DOTANOC PET/CT is routinely used to image neuroendocrine tumors (NETs). A case of lymphoma initially thought to be NET based on a positive Ga-DOTANOC PET/CT was recently seen at our institution. This prompted us to determine prospectively somatostatin receptor (SSTR) status in patients with lymphoma by immunohistochemical analysis of SSTR subtypes 2, 3 and 5 (SSTR) and Ga-DOTANOC PET/CT imaging.

Material And Methods: Twenty-one patients with newly diagnosed lymphoma were referred to Ga-DOTANOC and FDG PET/CT prior to any treatment. Tracer uptake was evaluated visually by two nuclear medicine specialists. Maximum standardized uptake values (SUVmax) were determined from 14 nodal and two extranodal regions with highest uptake in each patient. Lesions were then graded with Deauville score (1-5) on FDG PET/CT and modified Krenning score (0-4) on Ga-DOTANOC PET/CT, respectively. SSTR status was analyzed from routine biopsies of lymphomatous tissue and matched to corresponding PET/CT findings.

Results: About 20/21 patients had FDG-positive lymphoma (Deauville score ≥3). Uptake of Ga-DOTANOC was regarded as positive if Krenning score was ≥2 and resulted in 13/21 (62%) patients having Ga-DOTANOC-positive lymphomas. The highest uptake of Ga-DOTANOC was seen in Hodgkin's lymphoma of nodular sclerosis subtype and in diffuse large B-cell lymphoma (SUVmax median 9.8 and 9.7, respectively). Both cases showed strong SSTR immunopositivity in tumor cells. Some patients had SSTR immunopositivity predominantly in endothelial and dendritic cells and follicular centers of lymph nodes contributing to a positive PET/CT with probably low tumor-specific uptake. SSTR and SSTR were negative in most lymphoma subtypes.

Conclusions: According to this pilot study, Ga-DOTANOC PET/CT is positive in some lymphoma subtypes which express SSTRs. These tumors present a potential risk of being misinterpreted as NETs if a representative tumor sample is not available. Lymphomas with high expression of SSTRs may be amenable to treatments targeting these receptors.
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http://dx.doi.org/10.1080/0284186X.2017.1342864DOI Listing
February 2018

Decreased insulin-stimulated brown adipose tissue glucose uptake after short-term exercise training in healthy middle-aged men.

Diabetes Obes Metab 2017 10 6;19(10):1379-1388. Epub 2017 Jul 6.

Turku PET Centre, University of Turku, Turku, Finland.

Aims: To test the hypothesis that high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) improve brown adipose tissue (BAT) insulin sensitivity.

Participants And Methods: Healthy middle-aged men (n = 18, age 47 years [95% confidence interval {CI} 49, 43], body mass index 25.3 kg/m [95% CI 24.1-26.3], peak oxygen uptake (VO ) 34.8 mL/kg/min [95% CI 32.1, 37.4] ) were recruited and randomized into six HIIT or MICT sessions within 2 weeks. Insulin-stimulated glucose uptake was measured using 2-[ F]flouro-2-deoxy-D-glucose positron-emission tomography in BAT, skeletal muscle, and abdominal and femoral subcutaneous and visceral white adipose tissue (WAT) depots before and after the training interventions.

Results: Training improved VO (P = .0005), insulin-stimulated glucose uptake into the quadriceps femoris muscle (P = .0009) and femoral subcutaneous WAT (P = .02) but not into BAT, with no difference between the training modes. Using pre-intervention BAT glucose uptake, we next stratified subjects into high BAT (>2.9 µmol/100 g/min; n = 6) or low BAT (<2.9 µmol/100 g/min; n = 12) groups. Interestingly, training decreased insulin-stimulated BAT glucose uptake in the high BAT group (4.0 [2.8, 5.5] vs 2.5 [1.7, 3.6]; training*BAT, P = .02), whereas there was no effect of training in the low BAT group (1.5 [1.2, 1.9] vs 1.6 [1.2, 2.0] µmol/100 g/min). Participants in the high BAT group had lower levels of inflammatory markers compared with those in the low BAT group.

Conclusions: Participants with functionally active BAT have an improved metabolic profile compared with those with low BAT activity. Short-term exercise training decreased insulin-stimulated BAT glucose uptake in participants with active BAT, suggesting that training does not work as a potent stimulus for BAT activation.
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http://dx.doi.org/10.1111/dom.12947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5607085PMC
October 2017