High uptake on PSMA PET has been reported for several solid non-prostate cancers, including thyroid carcinoma. PSMA uptake in benign thyroid nodules has been reported as well. In this retrospective single institution study, we investigated the incidence and etiology of incidentally detected thyroid nodules with uptake on PSMA PET in a cohort of prostate cancer patients. We performed a search of our imaging database and identified PSMA PET demonstrating focal thyroid uptake. When multiple PSMA PET, only the first that demonstrated a thyroid nodule with PSMA-uptake was included. PET images were reviewed visually and by measuring the maximum standardized uptake value (SUVmax) of the focal thyroid uptake. Ultrasound images, TI-RADS scores, cytology (Bethesda grade) and surgical pathology reports were reviewed. 110 patients with focal thyroid PSMA-uptake who subsequently underwent ultrasound were included. Five had normal thyroid ultrasound. Five demonstrated two foci. FNAC was performed for 71 nodules in 68 patients. Cytology was nondiagnostic in 3 (4.2

Semi-quantitative uptake measurements are part of the PROMISE framework for PET/CT interpretation of tracers targeting the prostate-specific membrane antigen (PSMA), where tumor uptake is compared to uptake in reference tissues. [18F]PSMA-1007 has primarily hepatobiliary excretion and it is suggested to use spleen as reference tissue instead of liver. The aim of this study is to investigate the normal range and interpatient variability of [18F]PSMA-1007 uptake in reference tissue for prostate cancer patients, with particular focus on the splenic uptake. A total of 102 [18F]PSMA-1007 PET/CT scans of prostate cancer patients with biochemical recurrence (BCR) from three hospitals were included in the analysis. SUVmax and SUVmean measurements were performed in the blood pool, liver, spleen, and parotid glands. Results are reported as median with percentiles [5th, 95th]. For 15/102 (15

Background:Positron emission tomography (PET) with fluorine-18 or carbon-11 labeled choline (choline PET) has been found to have higher diagnostic accuracy for localizing hyperfunctioning parathyroid glands than other imaging methods. To evaluate if ultrasound (US) still has value in the diagnostic workup, we compared the findings on choline PET with US findings in patients with hyperparathyroidism (HPT). Methods:We retrospectively reviewed all patients with HPT who underwent a choline PET in the University Hospital of North Norway between 2019-2022. The indications for choline PET were negative or inconclusive localization with [99mTc]Tc-sestamibi scintigraphy and US, previous parathyroid surgery, or suspicion of multiglandular disease. Additionally, a focused parathyroid US was performed either before (67% of patients) or after the choline PET, without any blinding between modalities. Results:Sixty-two patients were included, of which 50 had been operated on at the time of analysis. Parathyroid tissue was removed in all patients, and multiglandular disease was found intraoperatively in 15 patients (30%). 96% of patients became normocalcemic after surgery. Diagnostic accuracy for choline PET and US was 98% and 89%, respectively, and 100% combined. Multiglandular disease was detected in 28% of patients by both modalities. Two patients with negative choline PET had a true positive US finding. Conclusions:Choline PET in combination with US performed by a radiologist specialized in neck US, successfully localized parathyroid disease in all operated patients. Both modalities detected 28% multiglandular disease. Findings on choline PET had better correspondence with intraoperative findings than US.

Radioiodine ablation therapy is commonly used for patients with well-differentiated thyroid cancer. False-positive radioiodine uptake in benign cystic lesions on post-therapy SPECT/CT presents a recognized diagnostic challenge. Here, we present the case of a 33-year-old woman who underwent total thyroidectomy, followed by I-131 radioiodine therapy. Her post-I-131 therapy SPECT/CT revealed incidental radioiodine uptake in a diaphragmatic mesothelial cyst, prompting further investigation. She subsequently underwent a dedicated liver MRI and excision biopsy, both of which were negative for thyroid cancer metastasis. This case highlights the importance of identifying benign sources of radioiodine uptake to avoid unnecessary interventions.

BackgroundProstate‐specific membrane antigen (PSMA) positron emission tomography (PET) can change management in a large fraction of patients with biochemically recurrent prostate cancer (BCR).PurposeTo investigate the added value of PET to MRI and CT for this patient group, and to explore whether the choice of the PET paired modality (PET/MRI vs. PET/CT) impacts detection rates and clinical management.Study TypeRetrospective.Subjects41 patients with BCR (median age [range]: 68 [55–78]).Field Strength/Sequence3T, including T1‐weighted gradient echo (GRE), T2‐weighted turbo spin echo (TSE) and dynamic contrast‐enhanced GRE sequences, diffusion‐weighted echo‐planar imaging, and a T1‐weighted TSE spine sequence. In addition to MRI, [18F]PSMA‐1007 PET and low‐dose CT were acquired on the same day.AssessmentImages were reported using a five‐point Likert scale by two teams each consisting of a radiologist and a nuclear medicine physician. The radiologist performed a reading using CT and MRI data and a joint reading between radiologist and nuclear medicine physician was performed using MRI, CT, and PET from either PET/MRI or PET/CT.Findings were presented to an oncologist to create intended treatment plans. Intrareader and interreader agreement analysis was performed.Statistical TestsMcNemar test, Cohen's κ, and intraclass correlation coefficients. A P‐value <0.05 was considered significant.Results7 patients had positive findings on MRI and CT, 22 patients on joint reading with PET/CT, and 18 patients joint reading with PET/MRI. For overall positivity, interreader agreement was poor for MR and CT (κ = 0.36) and almost perfect with addition of PET (PET/CT κ = 0.85, PET/MRI κ = 0.85). The addition of PET from PET/CT and PET/MRI changed intended treatment in 20 and 18 patients, respectively. Between joint readings, intended treatment was different for eight patients.Data ConclusionThe addition of [18F]PSMA‐1007 PET/MRI or PET/CT to MRI and CT may increase detection rates, could reduce interreader variability, and may change intended treatment in half of patients with BCR.Level of Evidence3Technical EfficacyStage 3

PURPOSE:The purpose was to evaluate the pathological nature of focal thyroid uptake seen in 11C-Choline PET/CT performed for prostate cancer. MATERIAL AND METHODS:The study was IRB-approved. All 11C-Choline PET/CT exam reports for studies performed between January 01, 2018, and July 30, 2021, in male patients with prostate cancer in our institution were retrospectively reviewed. Exams with "focal thyroid uptake" on their final report were selected. Patients with surgery or ablation in the thyroid prior to the PET/CT, proven parathyroid adenomas or absent thyroid ultrasound were excluded. Repeated PET/CT exams of same patient were excluded. PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value (SUVmax) of the focal thyroid uptake. Available thyroid ultrasound images, cytology and pathology reports were reviewed. Statistical analyses were performed. RESULTS:Out of 10,047 sequential 11C-Choline PET/CT studies, 318 reports included "focal thyroid uptake." About 128 of these studies were repeat exams and were excluded. Additional 87 patients were excluded, because the uptake was determined to be adjacent, rather than confined to the thyroid gland. Out of the remaining 103 patients, 74 patients had focal thyroid uptake and concurrent thyroid sonographic evaluation. Out of the 74 focal uptakes evaluated with ultrasound, 21 were presumed benign thyroid nodules based on the ultrasound and 53 had further evaluation with biopsy. Sixty three nodules were benign (21 presumed benign on ultrasound and 42 cytology or surgical pathology-proven), 9 nodules were malignant and 2 remained indeterminate. There was no significant difference between the SUVs of the benign and malignant groups (P > .3). CONCLUSION:In this retrospective study of patients with prostate cancer who underwent 11C-Choline PET/CT, we identified a group of patients who underwent thyroid ultrasound for incidental finding of focal 11C-Choline thyroid uptake. Incidence of malignancy in this group was 12%. Therefore, further investigation with ultrasound and possibly ultrasound-guided biopsy may be warranted when a choline avid thyroid nodule is found incidentally on choline PET.

Background:Treatment of castration-resistant metastatic prostate cancer with [¹⁷⁷Lu]PSMA radioligand. Case presentation:A man in his seventies with metastatic prostate cancer received castration therapy for four years, developing castration-resistant disease. PET/CT with [⁶⁸Ga]PSMA-11 showed high uptake in metastatic lymph nodes. The patient received 7.4 GBq [¹⁷⁷Lu]PSMA-I&T (Curium, Finland) as five treatments at five-week intervals. Five weeks after the first treatment, p-PSA dropped from 154 to 53 µg/L. Five weeks after the fifth treatment, p-PSA was 1.8 µg/L. [⁶⁸Ga]PSMA-11 PET/CT showed significant reduction in the size of metastases, with the largest decreasing in diameter from 10 to 4 mm. Seven months after the fifth treatment, p-PSA increased to 14.3 µg/L, and [⁶⁸Ga]PSMA-11 PET/ CT revealed additional skeletal metastases, while the lymph node metastases remained unchanged. Thus, the treatment had a good but temporary effect on the metastases. Interpretation:Treatment with [¹⁷⁷Lu]PSMA radioligand resulted in a temporary regression of the metastases.

The main objective is to discuss why treatment of non-prostate cancers with [177Lu]Lu-PSMA-radioligand achieved only low tumor dose in most published cases, despite high uptake on PSMA PET. We use a patient with renal cell carcinoma as an illustrative example. Furthermore, we discuss how the problem with early washout and low tumor dose might be overcome by using a radionuclide with shorter half-life, matching the target binding residence time. [68Ga]Ga-PSMA-11 PET/CT of a 56-year old man with metastatic renal cell carcinoma showed high lesion uptake. One dose of 6.9 GBq [177Lu]Lu-PSMA-I T was administrated. Post-therapy dosimetry was performed with SPECT/CT and whole-body planar imaging after 5, 24 and 48 h. Doses to target lesions were only 0.2–0.5 Gy. No treatment effect was achieved. Rapid tumor washout of [177Lu]Lu-PSMA-I T and low tumor dose despite high uptake of [68Ga]Ga-PSMA-11 are most likely caused by localization of PSMA-receptors on neovasculature rather than on the tumor cells, and unlike in prostate cancer cells, the PSMA-RL / PSMA-receptor complex is not internalized. To overcome the problem with early washout, the use of a radionuclide with shorter half-life matching the target binding residence time will be needed.

The primary aim was to evaluate whether anti-3-[18F]FACBC PET combined with conventional MRI correlated better with histomolecular diagnosis (reference standard) than MRI alone in glioma diagnostics. The ability of anti-3-[18F]FACBC to differentiate between molecular and histopathological entities in gliomas was also evaluated. In this prospective study, patients with suspected primary or recurrent gliomas were recruited from two sites in Norway and examined with PET/MRI prior to surgery. Anti-3-[18F]FACBC uptake (TBRpeak) was compared to histomolecular features in 36 patients. PET results were then added to clinical MRI readings (performed by two neuroradiologists, blinded for histomolecular results and PET data) to assess the predicted tumor characteristics with and without PET. Histomolecular analyses revealed two CNS WHO grade 1, nine grade 2, eight grade 3, and 17 grade 4 gliomas. All tumors were visible on MRI FLAIR. The sensitivity of contrast-enhanced MRI and anti-3-[18F]FACBC PET was 61 https://clinicaltrials.gov/study/NCT04111588

ThyroidVol. 33, No. 6 Letters To The EditorLetter to the Editor: Repeat Redifferentiation of Radioiodine Refractory BRAFV600E Mutated Thyroid Cancer with DabrafenibTrond Bogsrud, Marita Jacobsen, Jolanta Durski, Eivind Larsen, Ola Engelsen, Olav Inge Haskjold, Miguel Castillejo, Tore Bach-Gansmo, and Douglas Van NostrandTrond BogsrudAddress correspondence to: Trond Bogsrud, MD, PhD, PET-Centre, University Hospital of North Norway, Tromso 9038, Norway E-mail Address: [email protected]PET-Centre, University Hospital of North Norway, Tromso, Norway.PET-Centre, Aarhus University Hospital, Aarhus, Denmark.Search for more papers by this author, Marita JacobsenDepartment of Oncology, University Hospital of North Norway, Tromso, Norway.Search for more papers by this author, Jolanta DurskiDivision of Nuclear Medicine, Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.Search for more papers by this author, Eivind LarsenDepartment of Medical Physics, University Hospital of North Norway, Tromso, Norway.Search for more papers by this author, Ola EngelsenDepartment of Medical Physics, University Hospital of North Norway, Tromso, Norway.Search for more papers by this author, Olav Inge HaskjoldDepartment of Radiology, University Hospital of North Norway, Tromso, Norway.Search for more papers by this author, Miguel CastillejoPET-Centre, University Hospital of North Norway, Tromso, Norway.Search for more papers by this author, Tore Bach-GansmoPET-Centre, University Hospital of North Norway, Tromso, Norway.Search for more papers by this author, and Douglas Van NostrandDepartment of Nuclear Medicine, MedStar Washington Hospital Center, Georgetown University Medical Center, Washington, District of Columbia, USA.Search for more papers by this authorPublished Online:8 Jun 2023https://doi.org/10.1089/thy.2022.0651AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookXLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 33Issue 6Jun 2023 InformationCopyright 2023, Mary Ann Liebert, Inc., publishersTo cite this article:Trond Bogsrud, Marita Jacobsen, Jolanta Durski, Eivind Larsen, Ola Engelsen, Olav Inge Haskjold, Miguel Castillejo, Tore Bach-Gansmo, and Douglas Van Nostrand.Letter to the Editor: Repeat Redifferentiation of Radioiodine Refractory BRAFV600E Mutated Thyroid Cancer with Dabrafenib.Thyroid®.Jun 2023.771-773.http://doi.org/10.1089/thy.2022.0651Published in Volume: 33 Issue 6: June 8, 2023Online Ahead of Print:May 30, 2023Online Ahead of Editing: May 22, 2023PDF download

The aim of this prospective study was to investigate the prognostic value of metabolic tumor volume (MTV) and apparent diffusion coefficient (ADC) from baseline FDG PET/MRI compared to established clinical risk factors in terms of progression free survival (PFS) at 2 years in a cohort of diffuse large B-cell Lymphoma (DLBCL) and high-grade-B-cell lymphoma (HGBCL). Thirty-three patients and their baseline PET/MRI examinations were included. Images were read by two pairs of nuclear medicine physicians and radiologists for defining lymphoma lesions. MTV was computed on PET, and up to six lymphoma target lesions with restricted diffusion was defined for each PET/MRI examination. Minimum ADC (ADCmin) and the corresponding mean ADC (ADCmean) from the target lesion with the lowest ADCmin were included in the analyses. For the combined PET/MRI parameters, the ratio between MTV and the target lesion with the lowest ADCmin (MTV/ADCmin) and the corresponding ADCmean (MTV/ADCmean) was calculated for each patient. Clinical, histological, and PET/MRI parameters were compared between the treatment failure and treatment response group, while survival analyses for each variable was performed by using univariate Cox regression. In case of significant variables in the Cox regression analyses, Kaplan-Meier survival analyses with log-rank test was used to study the effect of the variables on PFS. ECOC PS scale ≥2 (p = 0.05) and ADCmean (p = 0.05) were significantly different between the treatment failure group (n = 6) and those with treatment response (n = 27). Survival analyses showed that ADCmean was associated with PFS (p = 0.02, [HR 2.3 for 1 SD increase]), while combining MTV and ADC did not predict outcome. In addition, ECOG PS ≥2 (p = 0.01, [HR 13.3]) and histology of HGBCL (p = 0.02 [HR 7.6]) was significantly associated with PFS. ADCmean derived from baseline MRI could be a prognostic imaging biomarker for DLBCL and HGBCL. Baseline staging with PET/MRI could therefore give supplementary prognostic information compared to today’s standard PET/CT.

Glioblastoma multiforme (GBM) is the most common glioma and standard therapies can only slightly prolong the survival. Neo-vascularization is a potential target to image tumor microenvironment, as it defines its brain invasion. We investigate [18F]rhPSMA-7.3 with PET/MRI for quantitative imaging of neo-vascularization in GBM bearing mice and human tumor tissue and compare it to [18F]FET and [18F]fluciclovine using PET pharmacokinetic modeling (PKM). [18F]rhPSMA-7.3, [18F]FET, and [18F]fluciclovine were i.v. injected with 10.5 ± 3.1 MBq, 8.0 ± 2.2 MBq, 11.5 ± 1.9 MBq (n = 28, GL261-luc2) and up to 90 min PET/MR imaged 21/28 days after surgery. Regions of interest were delineated on T2-weighted MRI for (i) tumor, (ii) brain, and (iii) the inferior vena cava. Time-activity curves were expressed as SUV mean, SUVR and PKM performed using 1-/2-tissue-compartment models (1TCM, 2TCM), Patlak and Logan analysis (LA). Immunofluorescent staining (IFS), western blotting, and autoradiography of tumor tissue were performed for result validation. [18F]rhPSMA-7.3 showed a tumor uptake with a tumor-to-background-ratio (TBR) = 2.1–2.5, in 15–60 min. PKM (2TCM) confirmed higher K1 (0.34/0.08, p = 0.0012) and volume of distribution VT (0.24/0.1, p = 0.0017) in the tumor region compared to the brain. Linearity in LA and similar k3 = 0.6 and k4 = 0.47 (2TCM, tumor, p = ns) indicated reversible binding. K1, an indicator for vascularization, increased (0.1/0.34, 21 to 28 days, p < 0.005). IFS confirmed co-expression of PSMA and tumor vascularization. [18F]fluciclovine showed higher TBR (2.5/1.8, p < 0.001, 60 min) and VS (1.3/0.7, p < 0.05, tumor) compared to [18F]FET and LA indicated reversible binding. VT increased (p < 0.001, tumor, 21 to 28 days) for [18F]FET (0.5–1.4) and [18F]fluciclovine (0.84–1.5). [18F]rhPSMA-7.3 showed to be a potential candidate to investigate the tumor microenvironment of GBM. Following PKM, this uptake was associated with tumor vascularization. In contrast to what is known from PSMA-PET in prostate cancer, reversible binding was found for [18F]rhPSMA-7.3 in GBM, contradicting cellular trapping. Finally, [18F]fluciclovine was superior to [18F]FET rendering it more suitable for PET imaging of GBM.

Purpose The study aims to evaluate whether combined F-18-FACBC PET/MRI could provide additional diagnostic information compared with MRI alone in brain metastases. Patients and Methods Eighteen patients with newly diagnosed or suspected recurrence of brain metastases received dynamic F-18-FACBC PET/MRI. Lesion detection was evaluated on PET and MRI scans in 2 groups depending on prior stereotactic radiosurgery (SRS group) or not (no-SRS group). SUVs, time-activity curves, and volumetric analyses of the lesions were performed. Results In the no-SRS group, 29/29 brain lesions were defined as "MRI positive." With PET, 19/29 lesions were detected and had high tumor-to-background ratios (TBRs) (D-max MR, >= 7 mm; SUVmax, 1.2-8.4; TBR, 3.9-25.9), whereas 10/29 lesions were undetected (D-max MR, <= 8 mm; SUVmax, 0.3-1.2; TBR, 1.0-2.7). In the SRS group, 4/6 lesions were defined as "MRI positive," whereas 2/6 lesions were defined as "MRI negative" indicative of radiation necrosis. All 6 lesions were detected with PET (D-max MR, >= 15 mm; SUVmax, 1.4-4.2; TBR, 3.6-12.6). PET volumes correlated and were comparable in size with contrast-enhanced MRI volumes but were only partially congruent (mean DSC, 0.66). All time-activity curves had an early peak, followed by a plateau or a decreasing slope. Conclusions F-18-FACBC PET demonstrated uptake in brain metastases from cancer of different origins (lung, gastrointestinal tract, breast, thyroid, and malignant melanoma). However, F-18-FACBC PET/MRI did not improve detection of brain metastases compared with MRI but might detect tumor tissue beyond contrast enhancement on MRI. F-18-FACBC PET should be further evaluated in recurrent brain metastases.

The aim of the current study was to investigate the diagnostic performance of FDG PET/MR compared to PET/CT in a patient cohort including Hodgkins lymphoma, diffuse large B-cell lymphoma, and high-grade B-cell lymphoma at baseline and response assessment. Sixty-one patients were examined with FDG PET/CT directly followed by PET/MR. Images were read by two pairs of nuclear medicine physicians and radiologists. Concordance for lymphoma involvement between PET/MR and the reference standard PET/CT was assessed at baseline and response assessment. Correlation of prognostic biomarkers Deauville score, criteria of response, SUVmax, SUVpeak, and MTV was performed between PET/MR and PET/CT. Baseline FDG PET/MR showed a sensitivity of 92.5% and a specificity 97.9% compared to the reference standard PET/CT (κ 0.91) for nodal sites. For extranodal sites, a sensitivity of 80.4% and a specificity of 99.5% were found (κ 0.84). Concordance in Ann Arbor was found in 57 of 61 patients (κ 0.92). Discrepancies were due to misclassification of region and not lesion detection. In response assessment, a sensitivity of 100% and a specificity 99.9% for all sites combined were found (κ 0.92). There was a perfect agreement on Deauville scores 4 and 5 and criteria of response between the two modalities. Intraclass correlation coefficient (ICC) for SUVmax, SUVpeak, and MTV values showed excellent reliability (ICC > 0.9). FDG PET/MR is a reliable alternative to PET/CT in this patient population, both in terms of lesion detection at baseline staging and response assessment, and for quantitative prognostic imaging biomarkers.

ABSTRACT A previously published model (Atkins) allows for calculation of 131I maximum tolerated activity on the basis of 48-hour whole-body retention of 131I on a pretherapy diagnostic scan. Our practice uses iodine 123I for diagnostic imaging of metastatic thyroid cancer for staging before 131I therapy, with images typically acquired 24 hours after administration of the radiopharmaceutical. We explored the feasibility of an additional 123I whole-body scan and retention measurement at 48 hours, with application of the model to estimate maximum tolerated activity of radioiodine before 131I treatment of metastatic thyroid cancer.

The aim of this guideline is to provide standards for the recommendation, performance, interpretation, and reporting of [18F]Fluciclovine PET/CT for prostate cancer imaging. These recommendations will help to improve accuracy, precision, and repeatability of [18F]Fluciclovine PET/CT for prostate cancer essentially needed for implementation of this modality in science and routine clinical practice.

Semi-automated quantitative measurement of metabolic tumor volume (MTV) for prognosis in diffuse large B-Cell lymphoma (DLBCL) has gained considerable interest lately. However, simple tumor volume measures may be inadequate for assessment of prognosis in DLBCL as other characteristics such as growth pattern and metabolic heterogeneity may be just as important. In addition, MTV measurements require delineation of tumor lesions by semi-automated software, which can be time-consuming. We hypothesized that a simple visual assessment of tumor volume performs as well as standardized MTV measurements in DLBCL prognostication. Quantitative and visual analyses of pre-therapy 18F-FDG PET/CT scans in 118 patients with newly diagnosed DLBCL were conducted. Quantitative analyses were performed using Hermes TumourFinder® to obtain MTV2.5 (SUV 2.5 cut-off) and MTV41 (41% SUVmax isocontour cut-off). Visual assessments included a binary prediction (good/poor prognosis) as well as tumor burden based on a visual analog scale (MTVVAS) and an estimated volume (eMTV). Three experienced nuclear medicine physicians who were blinded to clinical outcome performed visual evaluations. Progression-free survival was evaluated by Kaplan-Meier curves and log-rank test. Inter-observer variability was evaluated by Fleiss’ kappa for multiple observers. In the quantitative analysis, a ROC-determined MTV2.5 cut-off (log-rank p = 0.11) seemed to outperform MTV41 (log-rank p = 0.76) for PFS prediction. TLG2.5 (log-rank p = 0.14) and TLG41 (log-rank p = 0.34) were not associated with outcomes. By visual analysis, all three reviewers were able to stratify patients into good/poor prognosis (reviewer A log-rank p = 0.002, reviewer B log-rank p = 0.016, and reviewer C log-rank p = 0.012) with fair inter-observer agreement (Fleiss’ kappa 0.47). MTVVAS and eMTV were not consistently correlated with the outcome. Predictions of outcome after first-line treatment for DLBCL were surprisingly good when left to the unsupervised, subjective judgment of experienced readers of lymphoma 18F-FDG-PET/CT. The study highlights the importance of non-standardized clinical judgments and shows potential loss of valuable prognostic information when relying solely on semi-automated MTV measurements.