Whole-body parametric mapping of tumour perfusion in metastatic prostate cancer using long axial field-of-view [15O]H2O PET.

PURPOSE: Tumour perfusion is a nutrient-agnostic biomarker for cancer metabolic rate. Use of tumour perfusion for cancer growth assessment has been limited by complicated image acquisition, image analysis and limited field-of-view scanners. Long axial field-of-view (LAFOV) PET scan using [15O]H2O, allows quantitative assessment of whole-body tumour perfusion. We created a tool for automated creation of quantitative parametric whole-body tumour perfusion images in metastatic cancer. METHODS: Ten metastatic prostate cancer patients underwent dynamic LAFOV [15O]H2O PET (Siemens, Quadra) followed by [18F]PSMA-1007 PET. Perfusion was measured as [15O]H2O K1 (mL/min/mL) with a single-tissue compartment model and an automatically captured cardiac image-derived input function. Parametric perfusion images were automatically calculated using the basis-function method with initial voxel-wise delay estimation and a leading-edge approach. Subsequently, perfusion of volumes-of-interest (VOI) can be directly extracted from the parametric images. We used a [18F]PSMA-1007 SUV 4 fixed threshold for tumour delineation and transferred these VOIs to the perfusion map. RESULTS: For 8 primary tumours, 64 lymph node metastases, and 85 bone metastases, median tumour perfusion were 0.19 (0.15-0.27) mL/min/mL, 0.16 (0.13-0.27) mL/min/mL, and 0.26 (0.21-0.39), respectively. The correlation between calculated perfusion from time-activity-curves and parametric images was excellent (r = 0.99, p < 0.0001). CONCLUSION: LAFOV PET imaging using [15O]H2O enables truly quantitative parametric images of whole-body tumour perfusion, a potential biomarker for guiding personalized treatment and monitoring treatment response.

Splenic switch-off in [15O]H2O-positron emission tomography myocardial perfusion imaging using parametric blood flow images.

BACKGROUND: Evaluation of sufficient adenosine response constitutes a significant challenge in myocardial perfusion imaging (MPI). Splenic switch-off in MPI studies denotes a visually (qualitatively) reduced splenic radiotracer signal during adenosine stress and is considered indicative of sufficient cardiac vasodilation. In this study, we examined semi-quantitative and quantitative approaches to splenic switch-off assessment using [15O]H2O-PET with either summed activity images or calculated parametric splenic blood flow images. METHODS: Cohort 1: 90 clinical patients undergoing [15O]H2O MPI in whom adenosine response was considered clinically adequate were identified to characterize the corresponding splenic switch-off. Spleen stress/rest-ratio (SSR-ratio) was calculated as spleen stress signal intensity/spleen rest signal intensity on both summed activity and parametric blood flow images. Cohort 2: Twenty-five patients with repeat MPI due to suspected insufficient adenosine response were identified to observe if splenic switch-off on the initial MPI could predict the outcome of the repeat MPI. Cohort 3: Fifty-four patients who were considered adenosine responders on MPI and who had a coronary angiogram (CAG) follow-up within 3 months after MPI served as a separate validation group. RESULTS: Splenic switch-off was present in most patients with a clinically sufficient adenosine response (Cohort 1), illustrated by both visual (74.4%-86.7%), semi-quantitative (summed activity images) (85.6%), and quantitative (parametric blood flow images) (92.2%) evaluation, which corresponds to the distribution in patients with sufficient adenosine response and follow-up CAG (Cohort 3). In patients suspected of insufficient adenosine response on the initial MPI (Cohort 2), the repeat MPI only yielded different myocardial blood flow (MBF) results if the initial SSR-ratio was >0.90 on splenic parametric blood flow images. CONCLUSION: quantitative splenic switch-off assessment on parametric blood flow images was superior to the semi-quantitative splenic switch-off approach. Patients with a suspected insufficient initial adenosine response and SSR-ratio >0.90 can benefit from a repeat MPI. Thus, the integration of quantitative splenic switch-off using parametric blood flow images in the evaluation of adenosine response may support future clinical decision-making.

Extracardiac findings with increased perfusion during clinical O-15-H2O PET/CT myocardial perfusion imaging: A case series.

BACKGROUND: Coincidental extracardiac findings with increased perfusion were reported during myocardial perfusion imaging (MPI) with various retention radiotracers. Clinical parametric O-15-H2O PET MPI yielding quantitative measures of myocardial blood flow (MBF) was recently implemented at our facility. We aim to explore whether similar extracardiac findings are observed using O-15-H2O. METHODS AND RESULTS: All patients (2963) were scanned with O-15-H2O PET MPI according to international guidelines and extracardiac findings were collected. In contrast to parametric O-15-H2O MBF images, extracardiac perfusion was assessed using summed images. Biopsy histopathology and other imaging modalities served as reference standards. Various malignant lesions with increased perfusion were detected, including lymphomas, large-celled neuroendocrine tumour, breast, and lung cancer plus metastases from colonic and renal cell carcinomas. Furthermore, inflammatory and hyperplastic benign conditions with increased perfusion were observed: rib fractures, gynecomastia, atelectasis, sarcoidosis, pneumonia, chronic lung inflammation and fibrosis, benign lung nodule, chronic diffuse lung infiltrates, pleural plaques and COVID-19 infiltrates. CONCLUSIONS: Malignant and benign extracardiac coincidental findings with increased perfusion are readily visible and frequently seen on O-15-H2O PET MPI. We recommend evaluating the summed O-15-H2O PET images in addition to the low-dose CT attenuation images.

Tumour blood flow for prediction of human prostate cancer aggressiveness: a study with Rubidium-82 PET, MRI and Na+/K+-ATPase-density.

PURPOSE: Tumour blood flow (TBF) is a crucial determinant of cancer growth. Recently, we validated Rubidium-82 (82Rb) positron emission tomography (PET) for TBF measurement in prostate cancer (PCa) and found TBF and cancer aggressiveness positively correlated. The aims of the present study were to determine the ability of TBF for separating significant from insignificant PCa and to examine the relation to underlying Na+/K+-ATPase density, which is relevant as 82Rb is transported intracellularly via the Na+/K+-ATPase. METHODS: One hundred and two patients were included for pelvic 82Rb PET scan prior to magnetic resonance imaging (MRI)-guided prostate biopsy. Findings constituted 100 PCa lesions (86 patients) and 25 benign lesions (16 patients). Tumours were defined on MRI and transferred to 82Rb PET for TBF measurement. Immunohistochemical Na+/K+-ATPase staining was subsequently performed on biopsies. RESULTS: TBF was the superior predictor (rho = 0.68, p < 0.0001, inflammatory lesions excluded) of MRI-guided biopsy grade group (GG) over lowest apparent diffusion coefficient (ADC) value (rho = -0.23, p = 0.01), independent of ADC value and tumour volume (p < 0.0001). PET could separate GG-2-5 from GG-1 and benign lesions with an area under the curve (AUC), sensitivity, and specificity of 0.79, 96%, and 59%, respectively. For separating GG-3-5 from GG-1-2 and benign lesions the AUC, sensitivity, and specificity were 0.82, 95%, and 63%, respectively. Na+/K+-ATPase density per PCa cell profile was 38% lower compared with that of the benign prostate cell profiles. Neither cell density nor Na+/K+-ATPase density determined tumour 82Rb uptake. CONCLUSION: TBF is an independent predictor of PCa aggressiveness and deserves more attention, as it may be valuable in separating clinically significant from insignificant PCa.

Prospective comparative study of 18F-sodium fluoride PET/CT and planar bone scintigraphy for treatment response assessment of bone metastases in patients with prostate cancer.

AIM: To compare 18F-sodium fluoride positron emission tomography/computed tomography (NaF PET/CT) and 99mTc-labelled diphosphonate bone scan (BS) for the monitoring of bone metastases in patients with prostate cancer undergoing anti-cancer treatment. MATERIAL AND METHODS: Data from 64 patients with prostate cancer were included. The patients received androgen-deprivation therapy (ADT), next-generation hormonal therapy (NGH) or chemotherapy. The patients had a baseline scan and 1-3 subsequent scans during six months of treatment. Images were evaluated by experienced nuclear medicine physicians and classified for progressive disease (PD) or non-PD according to the Prostate Cancer Working Group 2 (PCWG-2) criteria. The patients were also classified as having PD/non-PD according to the clinical and prostate-specific antigen (PSA) responses. RESULTS: There was no difference between NaF PET/CT and BS in the detection of PD and non-PD during treatment (McNemar's test, p = .18). The agreement between BS and NaF PET/CT for PD/non-PD was moderate (Cohen's kappa 0.53, 95% confidence interval 0.26-0.79). Crude agreement between BS and NaF PET/CT for the assessment of PD/non-PD was 86% (89% for ADT, n = 28; 88% for NGH, n = 16, and 80% for chemotherapy, n = 20). In most discordant cases, BS found PD when NaF PET/CT did not, or BS detected PD on an earlier scan than NaF PET/CT. Biochemical progression (27%) occurred more frequently than progression on functional imaging (BS, 22% and NaF PET/CT, 14%). Clinical progression was rare (11%), and almost exclusively seen in patients receiving chemotherapy. CONCLUSION: There was no difference between NaF PET/CT and BS in the detection of PD and non-PD; however, BS seemingly detects PD by the PCWG-2 criteria earlier than NaF-PET, which might be explained by the fact that NaF-PET is more sensitive at the baseline scan.

PSMA PET/CT for Primary Staging of Prostate Cancer - An Updated Overview.

Prostate-specific membrane antigen PET/CT for primary staging of prostate cancer is becoming increasingly popular due to simultaneous assessment of whole-body disease burden, with superior sensitivity and specificity for detecting metastases compared to conventional imaging. PSMA PET in combination with multiparametric MRI (mpMRI) improves the sensitivity of assessment of extra-prostatic extension and seminal vesicle invasion compared to mpMRI alone, and may serve as a second line modality for image-guided biopsy in selected patients with negative mpMRI and/or negative primary biopsies. The superior diagnostic accuracy of PSMA PET/CT affects clinical decision-making with a change of clinical management in one-fourth of patients compared to conventional imaging. However, at present, the effect of implementing PSMA PET/CT for primary staging on patient outcomes is not clear, and prospective studies are warranted. There are several PSMA tracers with similar performance and minor individual pharmacokinetic differences such as higher rate of unspecific bone uptake with 18F-PSMA-1007, but on the other hand, lower urinary excretion, which could give an advantage in the detection of local recurrence. Proper training of the reporting physicians and knowledge of the pitfalls of the specific PSMA tracer used is of utmost importance for high-quality reading. We aim to provide an overview of the current literature and an update on the status of PSMA PET/CT for primary staging of prostate cancer.

Skeletal "Superscan" With 11 C-Methionine PET/CT in Polycythemia Vera.

ABSTRACT: 11 C-methionine PET/CT for parathyroid adenoma localization on a 60-year-old woman known with polycythemia vera revealed highly methionine-avid red bone marrow, an uptake pattern that has previously been described in hematological disease such as multiple myeloma. An equivalent skeletal "superscan" pattern in polycythemia vera has been described with other PET tracers, but this case illustrates that this pattern can be seen with 11 C-methionine PET/CT as well and can be added to the list of potential pitfalls.

Potential synergy between PSMA uptake and tumour blood flow for prediction of human prostate cancer aggressiveness.

BACKGROUND: Both prostate-specific membrane antigen (PSMA) uptake and tumour blood flow (TBF) correlate with International Society of Urological Pathology (ISUP) Grade Group (GG) and hence prostate cancer (PCa) aggressiveness. The aim of the present study was to evaluate the potential synergistic benefit of combining the two physiologic parameters for separating significant PCa from insignificant findings. METHODS: From previous studies of [82Rb]Rb positron emission tomography (PET) TBF in PCa, the 43 patients that underwent clinical [68Ga]Ga-PSMA-11 PET were selected for this retrospective study. Tumours were delineated on [68Ga]Ga-PSMA-11 PET or magnetic resonance imaging. ISUP GG was recorded from 52 lesions. RESULTS: [68Ga]Ga-PSMA-11 maximum standardized uptake value (SUVmax) and [82Rb]Rb SUVmax correlated moderately with ISUP GG (rho = 0.59 and rho = 0.56, both p < 0.001) and with each other (r = 0.65, p < 0.001). A combined model of [68Ga]Ga-PSMA-11 and [82Rb]Rb SUVmax separated ISUP GG > 2 from ISUP GG 1-2 and benign with an area-under-the-curve of 0.85, 96% sensitivity, 74% specificity, and 95% negative predictive value. The combined model performed significantly better than either tracer alone did (p < 0.001), primarily by reducing false negatives from five or six to one (p ≤ 0.025). CONCLUSION: PSMA uptake and TBF provide complementary information about tumour aggressiveness. We suggest that a combined analysis of PSMA uptake and TBF could significantly improve the negative predictive value and allow non-invasive separation of significant from insignificant PCa.

Avid 68Ga-PSMA Uptake in Periappendicular Abscess.

Ga-prostate-specific membrane antigen (PSMA) PET/CT for primary staging of high-risk prostate cancer revealed increased Ga-PSMA uptake in a known periappendicular abscess in a patient, who had undergone surgical drainage of the abscess 1 month earlier. The case presents another example of Ga-PSMA uptake in a benign infectious and inflammatory condition.

Renal Potassium Excretion Visualized on 82Rubidium PET/CT.

The positron emission tomography (PET) flow tracer 82Rubidium is a known potassium analogue. During our studies of tumor blood flow in prostate cancer, we found that approximately 10% of the patients had high urinary 82Rubidium activity. In roughly half of these patients, the increased renal rubidium/potassium excretion was either causing hypokalemia or explained by Thiazide treatment. In the other half, there was no obvious explanation or clinical consequence of the renal rubidium/potassium excretion. This is the first time enhanced renal potassium excretion is visualized on 82Rubidium PET/CT.

68Ga-PSMA Uptake in Escherichia coli Spondylodiscitis.

In a patient with recently diagnosed intermediate-risk prostate cancer, Ga-prostate-specific-membrane-antigen (PSMA) PET/CT for primary staging discovered increased Ga-PSMA uptake in spondylodiscitis in the thoracic spine. The bacteria Escherichia coli was found both in blood cultures and bone biopsies from the thoracic lesion. This case presents spondylodiscitis as a potential benign pitfall to be aware of when interpreting PSMA PET/CT in prostate cancer patients.

68Ga-PSMA Uptake in Anal Fistula on PET/CT Scan.

Ga-prostate-specific membrane antigen (PSMA) PET/CT scan for primary staging discovered increased Ga-PSMA uptake in a known anal fistula in a recently diagnosed high-risk prostate cancer patient. The patient had an ongoing history of surgical revisions of complex fistulas in the perianal region, contributing to active inflammation and infection. Recently, reports have demonstrated increased Ga-PSMA uptake in different benign inflammatory conditions. This case demonstrates another case of a benign condition associated with increased Ga-PSMA uptake.

Repeatability of tumor blood flow quantification with 82Rubidium PET/CT in prostate cancer - a test-retest study.

BACKGROUND: Non-invasive tumor blood flow (TBF) quantification is a candidate approach for risk stratification and monitoring of prostate cancer patients. Validation data have recently been published on prostate TBF measurement with the widely used positron emission tomography (PET) flow tracer 82Rubidium (82Rb). However, no test-retest data is available for TBF measurement with 82Rb PET in prostate cancer. Such information is important to determine the potential clinical usefulness of the technique. The aim of the present study was to determine the test-retest repeatability of TBF measurement with both dynamic and static 82Rb PET. METHODS: We recruited 10 low-to-high-risk prostate cancer patients scheduled for clinical prostate-specific membrane antigen (PSMA) PET/computed tomography (CT) or magnetic resonance imaging. Pelvic and cardiac static and dynamic 82Rb PET/CT were performed at baseline and repeated on a different day within 1 week. In total, 11 primary lesions were analyzed. RESULTS: For K1, standardized uptake values (SUV)max, SUVmean, and SUVpeak, prostate cancer 82Rb PET TBF has a repeatability of 32%, 51%, 53%, and 58% and an intraclass correlation of 0.98, 0.89, 0.88, and 0.88, respectively. CONCLUSION: Dynamic 82Rb PET/CT with kinetic modeling measures TBF in prostate cancer with high repeatability, which allows identification of blood flow changes of 32%. Static late-uptake 82Rb PET/CT is inferior, and only intra-individual blood flow changes above 51% can hence be recognized.

Benign Esophageal Findings on 68Ga-Prostate-Specific Membrane Antigen PET/CT Scan.

In 2 high-risk prostate cancer patients, PET scans revealed focally increased Ga-prostate-specific membrane antigen uptake in the distal esophagus. Both patients had hiatus herniation on gastroscopy, and esophageal biopsies revealed acute and chronic inflammation in both patients and a benign hyperplastic polyp in one of the patients. Recently, reports have demonstrated that inflammation can cause false-positive findings on Ga-prostate-specific membrane antigen PET/CT, and these cases present this phenomenon in the esophagus as well.

Intense 68Ga-PSMA Uptake in Diverticulum of the Sigmoid Colon.

We present a case of a diverticulum of the sigmoid colon with intense prostate-specific membrane antigen (PSMA) activity on Ga-PSMA PET/CT. CT scan and colonoscopy showed no signs of inflammation or malignancy. This case presents an addition to the collection of benign pitfalls when reporting PSMA PET/CT; however, a Ga-PSMA up-taking focus in the colon should always cause further examination, as malignant etiology must be ruled out.

Follicular thyroid cancer avid on C-11 Methionine PET/CT.

A case of follicular thyroid cancer with intense focal Methionine uptake on 11C-Methionine PET/CT is reported here. The use of 11C-Methionine PET in differentiated thyroid cancer is currently being investigated as a surrogate tracer compared to the more widely used 18F-FDG PET. This case illustrates the potential incremental value of this modality, not only in the localizing of parathyroid adenoma, but also indicating that 11C-Methionine PET might have a potential of increasing the pretest likelihood of thyroid malignancy in a cold nodule with highly increased Sestamibi uptake. LEARNING POINTS: 11C-Methionine PET/CT and 18F-Fluorocholine PET/CT often visualizes the parathyroid adenoma in case of negative Tc-99m-MIBI SPECT/CT.A cold nodule in Tc-99m Pertechnetat thyroid scintigraphy with a negative Sestamibi scintigraphy has a very low probability of being malignant.However, the pretest likelihood of thyroid cancer in a cold nodule with increased Sestamibi uptake is low.11C-Methionine PET might have a potential incremental value in increasing the pretest likelihood of thyroid malignancy in a cold nodule with highly increased Sestamibi uptake.

68Ga-PSMA Avid Primary Adenocarcinoma of the Lung With Complementary Low 18F-FDG Uptake.

Ga-PSMA PET/CT scan on a 70-year-old man with recently diagnosed prostate cancer revealed a spiculating nodule in the apex of the left lung with intense Ga-PSMA uptake. The nodule had no pathological F-FDG uptake and turned out to be a primary adenocarcinoma of the lung. Cases with complementary pattern of uptake in F-FDG and Ga-PSMA in metastatic clear cell renal carcinoma and in well-differentiated hepatocellular carcinoma have previously been reported; however, this case illustrates that this unusual pattern can also be present in primary lung cancer.

Benign Traumatic Rib Fracture: A Potential Pitfall on 68Ga-Prostate-Specific Membrane Antigen PET/CT for Prostate Cancer.

Two, respectively, 72- and 76-year-old men with recently diagnosed high-risk prostate cancer were referred for primary staging with Ga-prostate-specific membrane antigen (PSMA) PET/CT. In both patients, the PET scans revealed increased Ga-PSMA uptake in, respectively, 3 and 4 rib fractures, characteristically placed as "pearls on a string." These cases illustrate important pitfalls when reporting PSMA PET.

Lumbar Osteophyte Avid on 68Ga-Prostate-Specific Membrane Antigen PET/CT.

A 75-year-old man with recently diagnosed high-risk prostate cancer was referred for primary staging with Ga-prostate-specific membrane antigen (PSMA) PET/CT. The scan revealed intense Ga-PSMA uptake in a lumbar osteophyte on the right side of level L2/L3, whereas several other spinal osteophytes showed no Ga-PSMA uptake. MRI findings in the L3 vertebra was consistent with a benign Modic type 1 lesion, but MRI showed no signs of malignancy in the osteophyte with high Ga-PMSA uptake. This case presents an osteophyte as an addition to the list of potential benign pitfalls to be aware of when interpreting Ga-PSMA PET/CT.

Metastases From Colorectal Cancer Avid on 68Ga-PSMA PET/CT.

Ga-PSMA PET/CT is currently used for detection of prostate cancer including metastases, even at low prostate-specific antigen values. A grown number of reports have shown increased uptake of PSMA in neovessels of nonprostatic malignancies including lung cancer, and recently a case report has demonstrated increased PSMA uptake in colorectal adenocarcinoma. In this case report, we demonstrate increased Ga-PMSA uptake on PET/CT in metastases from previously treated colon adenocarcinoma, and it illustrates the importance of histology of suspicious lesions on Ga-PSMA PET/CT.