The additional value of 68Ga-PSMA PET/CT SUVmax in predicting ISUP GG ≥ 2 and ISUP GG ≥ 3 prostate cancer in biopsy.

BACKGROUND: Prebiopsy magnetic resonance imaging (MRI) increases the detection rate of clinically significant prostate cancer (csPCa). Prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA PET/CT) maximum standardized uptake value (SUVmax) of the prostate may offer additional value in predicting the likelihood of csPCa in biopsy. METHODS: A single-center cohort study involving patients with biopsy-proven PCa who underwent both MRI and PSMA PET/CT between 2020 and 2021. Logistic regression models were developed for International Society of Urological Pathology (ISUP) Grade Group (GG) ≥ 2 and GG ≥ 3 using noninvasive prebiopsy parameters: age, (log-)prostate-specific antigen (PSA) density, PI-RADS 5 lesion presence, extraprostatic extension (EPE) on MRI, and SUVmax of the prostate. Models with and without SUVmax were compared using Likelihood ratio tests and area under the curve (AUC). DeLong's test was used to compare the AUCs. RESULTS: The study included 386 patients, with 262 (68%) having ISUP GG ≥ 2 and 180 (47%) having ISUP GG ≥ 3. Including SUVmax significantly improved both models' goodness of fit (p < 0.001). The GG ≥ 2 model had a higher AUC with SUVmax 89.16% (95% confidence interval [CI]: 86.06%-92.26%) than without 87.34% (95% CI: 83.93%-90.76%) (p = 0.026). Similarly, the GG ≥ 3 model had a higher AUC with SUVmax 82.51% (95% CI: 78.41%-86.6%) than without 79.33% (95% CI: 74.84%-83.83%) (p = 0.003). The SUVmax inclusion improved the GG ≥ 3 model's calibration at higher probabilities. CONCLUSION: SUVmax of the prostate on PSMA PET/CT potentially improves diagnostic accuracy in predicting the likelihood of csPCa in prostate biopsy.

The association of quantitative PSMA PET parameters with pathologic ISUP grade: an international multicenter analysis.

PURPOSE: To assess if PSMA PET quantitative parameters are associated with pathologic ISUP grade group (GG) and upgrading/downgrading. METHODS: PCa patients undergoing radical prostatectomy with or without pelvic lymph node dissection staged with preoperative PSMA PET at seven referral centres worldwide were evaluated. PSMA PET parameters which included SUVmax, PSMAvolume, and total PSMA accumulation (PSMAtotal) were collected. Multivariable logistic regression evaluated the association between PSMA PET quantified parameters and surgical ISUP GG. Decision-tree analysis was performed to identify discriminative thresholds for all three parameters related to the five ISUP GGs The ROC-derived AUC was used to determine whether the inclusion of PSMA quantified parameters improved the ability of multivariable models to predict ISUP GG ≥ 4. RESULTS: A total of 605 patients were included. Overall, 2%, 37%, 37%, 10% and 13% patients had pathologic ISUP GG1, 2, 3, 4, and 5, respectively. At multivariable analyses, all three parameters SUVmax, PSMAvolume and PSMAtotal were associated with GG ≥ 4 at surgical pathology after accounting for PSA and clinical T stage based on DRE, hospital and radioligand (all p < 0.05). Addition of all three parameters significantly improved the discrimination of clinical models in predicting GG ≥ 4 from 68% (95%CI 63 - 74) to 74% (95%CI 69 - 79) for SUVmax, 72% (95%CI 67 - 76) for PSMAvolume, 74% (70 - 79) for PSMAtotal and 75% (95%CI 71 - 80) when all parameters were included (all p < 0.05). Decision-tree analysis resulted in thresholds that discriminate between GG (SUVmax 0-6.5, 6.5-15, 15-28, > 28, PSMAvol 0-2, 2-9, 9-20 and > 20 and PSMAtotal 0-12, 12-98 and > 98). PSMAvolume was significantly associated with GG upgrading (OR 1.03 95%CI 1.01 - 1.05). In patients with biopsy GG1-3, PSMAvolume ≥ 2 was significantly associated with higher odds for upgrading to ISUP GG ≥ 4, compared to PSMAvolume < 2 (OR 6.36, 95%CI 1.47 - 27.6). CONCLUSION: Quantitative PSMA PET parameters are associated with surgical ISUP GG and upgrading. We propose clinically relevant thresholds of these parameters which can improve in PCa risk stratification in daily clinical practice.

Current research topics in FAPI theranostics: a bibliometric analysis.

PURPOSE: The study aimed to provide a comprehensive bibliometric overview of the current scientific publications on fibroblast activation protein inhibitor (FAPI) positron emission tomography imaging and radionuclide therapy. METHODS: A PubMed search was performed to identify all MEDLINE-indexed publications on FAPI imaging and radionuclide therapy. The last update was performed on 31 May 2022. An online database of this literature was created, and hierarchical topic-related tags were subsequently assigned to all relevant studies. Frequency analysis was used to evaluate the distribution of the following characteristics: first author's country of origin, journal of publication, study design, imaging techniques and radiopharmaceutical used, histopathological correlation, the type of cancer, and benign disease/uptake types evaluated. RESULTS: A total of 294 relevant publications on original studies were identified, consisting of 209 (71%) case reports/series and 85 cohort studies (29%). The majority of studies focused on imaging topics, predominantly comparing uptake on FAPI-PET/CT with 2-[18F]FDG-PET/CT, anatomical imaging, and/or histopathology results. 68% of studies focused on malignancies, with gastro-intestinal cancer, hepato-pancreato-biliary cancer, mixed cancers/metastases, lung cancer, sarcoma, head and neck cancer, and breast cancer being the most frequently reported. 42% of studies focused on benign disease categories, with cardiovascular, musculoskeletal, HPB, head and neck, and IgG4-related disease as most common categories. 16/294 (5%) studies focused on radionuclide therapy, with preliminary reports of acceptable toxicity profiles, tumour activity retention, and suggestion of disease control. CONCLUSION: FAPI research is rapidly expanding from diagnostic studies in malignancies and benign diseases to the first reports of salvage radionuclide therapy. The research activity needs to shift now from low-level-of-evidence case reports and series to prospectively designed studies in homogenous patient groups to provide evidence on how and in which clinical situations FAPI theranostics can be of added value to clinical care. We have provided an overview of current research topics to build upon.

Sentinel Lymph Node Mapping in Breast Cancer Patients Through Fluorescent Imaging Using Indocyanine Green: The INFLUENCE Trial.

OBJECTIVE: The aim was to compare the (sentinel) lymph node detection rate of indocyanine green (ICG)-fluorescent imaging versus standard-of-care 99m Tc-nanocoilloid for sentinel lymph node (SLN)-mapping. BACKGROUND: The current gold standard for axillary staging in patients with breast cancer is sentinel lymph node biopsy (SLNB) using radio-guided surgery using radioisotope technetium ( 99m Tc), sometimes combined with blue dye. A promising alternative is fluorescent imaging using ICG. METHODS: In this noninferiority trial, we enrolled 102 consecutive patients with invasive early-stage, clinically node-negative breast cancer. Patients were planned for breast conserving surgery and SLNB between August 2020 and June 2021. The day or morning before surgery, patients were injected with 99m Tc-nanocolloid. In each patient, SLNB was first performed using ICG-fluorescent imaging, after which excised lymph nodes were tested with the gamma-probe for 99m Tc-uptake ex vivo, and the axilla was checked for residual 99m Tc-activity. The detection rate was defined as the proportion of patients in whom at least 1 (S)LN was detected with either tracer. RESULTS: In total, 103 SLNBs were analyzed. The detection rate of ICG-fluorescence was 96.1% [95% confidence interval (95% CI)=90.4%-98.9%] versus 86.4% (95% CI=78.3%-92.4%) for 99m Tc-nanocoilloid. The detection rate for pathological lymph nodes was 86.7% (95% CI=59.5%-98.3%) for both ICG and 99m Tc-nanocoilloid. A median of 2 lymph nodes were removed. ICG-fluorescent imaging did not increase detection time. No adverse events were observed. CONCLUSIONS: ICG-fluorescence showed a higher (S)LN detection rate than 99m Tc-nanocoilloid, and equal detection rate for pathological (S)LNs. ICG-fluorescence may be used as a safe and effective alternative to 99m Tc-nanocoilloid for SLNB in patients with early-stage breast cancer.

Prospective Validation of Gallium-68 Prostate Specific Membrane Antigen-Positron Emission Tomography/Computerized Tomography for Primary Staging of Prostate Cancer.

PURPOSE: Prospective validation of 68Ga prostate specific membrane antigen positron emission tomography/computerized tomography is lacking in initial staging of prostate cancer. In this study we evaluated the diagnostic accuracy of 68Ga prostate specific membrane antigen positron emission tomography/computerized tomography for detecting lymph node metastasis in patients with intermediate-high risk prostate cancer. MATERIALS AND METHODS: Patients with newly diagnosed prostate cancer and negative bone scan findings at greater than 10% MSKCC (Memorial Sloan Kettering Cancer Center) risk for lymph node metastasis were prospectively included in study from October 2017 to October 2018. In candidates for extended pelvic lymph node dissection 68Ga prostate specific membrane antigen positron emission tomography/computerized tomography was performed prior to planned surgery. Scan results were evaluated in a second tumor board meeting to assess a potential change of management. Sensitivity, specificity, and positive and negative predictive value for detecting lymph node metastasis were calculated per patient and per resection template using histopathology as the reference. A positron emission tomography based change of management was also reported. RESULTS: A total of 103 patients were eligible for analysis and 97 extended pelvic lymph node dissections were performed. In 41 patients (42.3%) there was a total of 85 lymph node metastases. Positron emission tomography was positive in 17 patients, resulting in 41.5% patient based sensitivity (95% CI 26.7-57.8) for detecting lymph node metastasis. The patient based specificity rate was 90.9% (95% CI 79.3-96.6), and positive and negative predictive values were 77.3% (95% CI 54.2-91.3) and 67.6% (95% CI 55.6-77.7), respectively. A positron emission tomography based change of treatment was observed in 13 patients (12.6%). CONCLUSIONS: In patients with newly diagnosed prostate cancer at greater than 10% MSKCC risk for lymph node involvement 68Ga prostate specific membrane antigen positron emission tomography/computerized tomography detected lymph node metastasis with high specificity and moderate sensitivity. This led to a treatment change in 12.6% of patients.

Real-world outcomes of radium-223 dichloride for metastatic castration resistant prostate cancer.

Aim: Timing of radium-223 (Ra-223) in metastatic castration-resistant prostate cancer (mCRPC) remains challenging due to alternative options and short window of opportunity. Methods: Ra-223 treated patients in the CAPRI-registry were included. Outcomes were evaluated based on treatment line of Ra-223. Results: Out of 285 patients, 49% received Ra-223 in line ≥3. 51% completed six Ra-223 injections and 34% had a symptomatic skeletal event after first Ra-223 without differences between subgroups. After correction of known prognostic factors Ra-223 in line ≥3 (HR: 3.267; 95% CI: 1.689-6.317; p < 0.01) remained associated with worse OS. Conclusion: In the Netherlands, Ra-223 was mainly started as second or third mCRPC-treatment in 2014-2018. Later timing of Ra-223 did affect OS, but not treatment completion and occurrence of symptomatic skeletal events.

Measuring the actual I-131 thyroid uptake curve with a collar detector system: a feasibility study.

Radionuclide therapy using I-131 is commonly used for the treatment of benign thyroid diseases. The therapeutic dose to be administered is calculated based on the type of disease, the volume of the thyroid, and the measured uptake percentage. This methodology assumes a similar biological half-life of iodine, whereas in reality a large variation in biological half-life is observed. More knowledge about the actual biological half-life of iodine for individual patients will improve the quantification of the delivered radiation dose during radioiodine therapy and could aid the evaluation of the success of the therapy. In this feasibility study we used a novel measurement device [Collar Therapy Indicator (CoTI)] to measure the uptake curve of patients undergoing I-131 radioiodine therapy. The CoTI device is a light-weight wearable device that contains two independent gamma radiation detectors that are placed in a collar. By comparing results of thyroid uptake measurements with results obtained with a gamma camera, the precision of the system is demonstrated. Additionally, for three patients the uptake curve is measured during 48 h of admission in the hospital. The presented results demonstrate the feasibility of the new measurement device to measure the uptake curve during radioiodine therapy.

Gallium-68 Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography in Active Surveillance for Prostate Cancer Trial (PASPoRT).

BACKGROUND: The use of clinical parameters, including prebiopsy magnetic resonance imaging (MRI), to decide between active surveillance (AS) and active therapy for prostate cancer (PCa) leads to imperfect selection. Additional prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) imaging may improve risk stratification. OBJECTIVE: To study risk stratification and patient selection for AS with the addition of PSMA PET/CT to standard practice. DESIGN, SETTING, AND PARTICIPANTS: A single-centre prospective cohort study (NL69880.100.19) enrolled patients recently diagnosed with PCa who started AS. At diagnosis, all participants had undergone prebiopsy MRI and targeted biopsy for visualised lesions. Patients underwent an additional [68Ga]-PSMA PET/CT and targeted biopsy of all PSMA lesions with a maximum standardised uptake value (SUVmax) of ≥4 not covered by previous biopsies. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the number needed to scan (NNS) to detect one patient with upgrading. The study was powered to detect an NNS of 10. Regarding secondary outcomes, univariate logistic regressions analyses were performed on all patients and on the patients who received additional PSMA targeted biopsies on the likelihood of upgrading. RESULTS AND LIMITATIONS: A total of 141 patients were included. Additional PSMA targeted biopsies were performed in 45 (32%) patients. In 13 (9%) patients, upgrading was detected: nine grade group (GG) 2, two GG 3, one GG 4, and one GG 5. The NNS was 11 (95% confidence interval 6-18). Of all participants, PSMA PET/CT and targeted biopsies yielded upgrading most frequently in patients with negative MRI (Prostate Imaging Reporting and Data System [PI-RADS] 1-2). Of patients who received additional PSMA targeted biopsies, upgrading was most frequently found in those with higher prostate-specific antigen density and negative MRI. Limitations included the lack of comparison with standard repeat biopsy, no central review of MRI, and possibility of biopsy sampling error. CONCLUSIONS: PSMA PET/CT can further improve PCa risk stratification and selection for AS patients diagnosed after MRI and targeted biopsies. PATIENT SUMMARY: Prostate-specific membrane antigen positron emission tomography/computed tomography and additional targeted prostate biopsies can identify more aggressive prostate cancer cases previously missed in patients recently started with expectant management for favourable-risk prostate cancer.

[PSMA PET, an important addition in prostate cancer diagnostics]. / PSMA-PET: aanwinst voor de prostaatkankerdiagnostiek.

PSMA PET/CT is a diagnostic technique for patients with prostate cancer. It makes use of a radioligand that specifically binds to 'prostate specific membrane antigen' (PSMA), expressed by the prostate cancer cells. PSMA PET has proven to be highly effective in prostate cancer diagnostics in both primary staging and re-staging. PSMA PET/CT has a much higher accuracy than traditional CT and skeletal scintigraphy for the detection of metastases, allowing metastases to be detected in an earlier stage. The clinical relevance of the improved detection is now under investigation. Staging with PSMA PET/CT sometimes leads to avoiding surgery because distant metastases are found that were not detected with conventional imaging. In the Netherlands, PSMA PET/CT is now indicated both in primary prostate cancer diagnostics for the detection of metastases and for the detection of biochemical recurrence after prostatectomy or after radiotherapy.

Cost-effectiveness of the implementation of [68Ga]Ga-PSMA-11 PET/CT at initial prostate cancer staging.

BACKGROUND: Despite its high specificity, PSMA PET/CT has a moderate to low sensitivity of 40-50% for pelvic lymph node detection, implicating that a negative PSMA PET/CT cannot rule out lymph node metastases. This study investigates a strategy of implementing PSMA PET/CT for initial prostate cancer staging and treatment planning compared to conventional diagnostics. In this PSMA PET/CT strategy, a bilateral extended pelvic lymph node dissection (ePLND) is only performed in case of a negative PSMA PET/CT; in case of a positive scan treatment planning is solely based on PSMA PET/CT results. METHOD: A decision table and lifetime state transition model were created. Quality-adjusted life years and health care costs were modelled over lifetime. RESULTS: The PSMA PET/CT strategy of treatment planning based on initial staging with [68Ga]Ga-PSMA-11 PET/CT results in cost-savings of €674 and a small loss in quality of life (QoL), 0.011 QALY per patient. The positive effect of [68Ga]Ga-PSMA-11 PET/CT was caused by abandoning both an ePLND and unnecessary treatment in iM1 patients, saving costs and resulting in higher QoL. The negative effect was caused by lower QoL and high costs in the false palliative state, due to pN1lim patients (≤ 4 pelvic lymph node metastases) being falsely diagnosed as iN1ext (> 4 pelvic lymph node metastases). These patients received subsequently palliative treatment instead of potentially curative therapy. CONCLUSION: Initial staging and treatment planning based on [68Ga]Ga-PSMA-11 PET/CT saves cost but results in small QALY loss due to the rate of false positive findings.

Symptomatic Skeletal Events and the Use of Bone Health Agents in a Real-World Treated Metastatic Castration Resistant Prostate Cancer Population: Results From the CAPRI-Study in the Netherlands.

BACKGROUND: Patients with metastatic castration resistant prostate cancer (mCRPC) are at risk of symptomatic skeletal events (SSE). Bone health agents (BHA, ie bisphosphonates and denosumab) and new life-prolonging drugs (LPDs) can delay SSEs. The aim of this study is to investigate the use of BHAs in relation to SSEs in treated real-world mCRPC population. PATIENTS AND METHODS: We included patients from the CAPRI registry who were treated with at least one LPD and diagnosed with bone metastases prior to the start of first LPD (LPD1). Outcomes were SSEs (external beam radiation therapy (EBRT) to the bone, orthopedic surgery, pathologic fracture or spinal cord compression) and SSE-free survival (SSE-FS) since LPD1. RESULTS: One-thousand nine hundred and twenty-three patients were included with a median follow-up from LPD1 of 16.7 months. Fifty-two percent (n = 996) started BHA prior or within 4 weeks after the start of LPD1 (early BHA). In total, 41% experienced at least one SSE. SSE incidence rate was 0.29 per patient year for patients without BHA and 0.27 for patients with early BHA. Median SSE-FS from LPD1 was 12.9 months. SSE-FS was longer in patients who started BHA early versus patients without BHA (13.2 vs. 11.0 months, P = .001). CONCLUSION: In a real-world population we observed an undertreatment with BHAs, although patients with early BHA use had lower incidence rates of SSEs and longer SSE-FS. This finding was irrespective of type of SSE and presence of risk factors. In addition to LPD treatment, timely initiation of BHAs is recommended in bone metastatic CRPC-patients with both pain and/or opioid use and prior SSE.

High-Intensity Care in the End-of-Life Phase of Castration-Resistant Prostate Cancer Patients: Results from the Dutch CAPRI-Registry.

Background: Intensive end-of-life care (i.e., the overuse of treatments and hospital resources in the last months of life), is undesirable since it has a minimal clinical benefit with a substantial financial burden. The aim was to investigate the care in the last three months of life (end-of-life [EOL]) in castration-resistant prostate cancer (CRPC). Methods: Castration-resistant prostate cancer registry (CAPRI) is an investigator-initiated, observational multicenter cohort study in 20 hospitals retrospectively including patients diagnosed with CRPC between 2010 and 2016. High-intensity care was defined as the initiation of life-prolonging drugs (LPDs) in the last month, continuation of LPD in last 14 days, >1 admission, admission duration ≥14 days, and/or intensive care admission in last three months of life. Descriptive and binary logistic regression analyses were performed. Results: High-intensity care was experienced by 41% of 2429 patients in the EOL period. Multivariable analysis showed that age (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.97-0.99), performance status (OR 0.57, 95% CI 0.33-0.97), time from CRPC to EOL (OR 0.98, 95% CI 0.97-0.98), referral to a medical oncologist (OR 1.99, 95% CI 1.55-2.55), prior LPD treatment (>1 line OR 1.72, 95% CI 1.31-2.28), and opioid use (OR 1.45, 95% CI 1.08-1.95) were significantly associated with high-intensity care. Conclusions: High-intensity care in EOL is not easily justifiable due to high economic cost and little effect on life span, but further research is awaited to give insight in the effect on patients' and their caregivers' quality of life.

Oligometastatic Prostate Cancer: Results of a Dutch Multidisciplinary Consensus Meeting.

BACKGROUND: Oligometastatic prostate cancer (OMPC) is a heterogeneous disease state that is imperfectly understood, and its clinical implications are unclear. OBJECTIVE: To determine the consensus of a Dutch multidisciplinary expert panel on biological aspects, treatment goals, and management of OMPC in daily clinical practice. DESIGN, SETTING, AND PARTICIPANTS: The study comprised a modified Delphi method including an explorative survey with various statements and questions, followed by a consensus meeting to discuss and determine the agreement with revised statements and related items. The panel consisted of 34 Dutch representatives from urology, medical and radiation oncology, radiology, nuclear medicine, and basic research. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Agreement was determined with statements (five-point scale). Consensus was defined as ≥75% panel agreement with a statement. RESULTS AND LIMITATIONS: Consensus existed for 56% of statements. The panel agreed that OMPC comprises a limited metastatic spread in the hormone-sensitive setting, in both the synchronous and the metachronous presentation. Limited metastatic spread was believed to involve three to five metastases and a maximum of two organs. Prostate-specific membrane antigen positron emission tomography/computed tomography scan was currently perceived as the most accurate diagnostic imaging modality. Although there was a consensus that targeted treatment of all metastases in OMPC will delay further dissemination of the disease, opinions on specific treatment regimens were divided. Panel outcomes were limited by the lack of scientific evidence on OMPC. CONCLUSIONS: A multidisciplinary panel reached a consensus that OMPC is a specific disease state requiring a tailored treatment approach. OMPC registries and clinical studies should focus on both the biology and the clinical parameters in relation to optimal treatment strategies in synchronous and metachronous OMPC. PATIENT SUMMARY: A group of Dutch medical specialists agreed that prostate cancer patients having few metastases may benefit from a new therapeutic approach. Clinical studies need to determine which treatment is best for each specific situation.

Imaging of fibrogenesis in patients with idiopathic pulmonary fibrosis with cis-4-[(18)F]-Fluoro-L: -proline PET.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease for which no single diagnostic modality is able to evaluate the activity of the disease process. Cis-4-(18)F-fluoro-L: -proline ((18)F-proline) was shown in animal studies to be a reliable marker for fibrosis formation. We tested this candidate radioligand for imaging of fibrogenesis in patients with IPF. METHODS: Five patients with IPF proven by lung biopsy and computed tomography were included. Furthermore, we also included one patient with non-specific interstitial pneumonia (NSIP) and scleroderma and one with NSIP and organising pneumonia. Positron emission tomography (PET) acquisition was performed 1, 2 and 3h after injection of 400MBq (18)F-proline. We scored (18)F-proline activity visually and quantitatively by calculating the activity in the regions of interest over lung, liver and mediastinum. RESULTS: We found low uptake of (18)F-proline in the lungs of all patients with IPF. The highest uptake was seen at 2h post-injection, with a decline at 3h past injection. The differences in lung uptake between patients were small, except for one patient with NSIP and organising pneumonia who had a slightly higher (18)F-proline uptake. No significant correlations between (18)F-proline uptake and clinical parameters were found. CONCLUSIONS: Due to the low pulmonary uptake of (18)F-proline in patients with IPF, (18)F-proline does not seem to be a suitable radioligand to evaluate the activity of fibrosis formation in patients with IPF. The low uptake in the lungs of patients with interstitial fibrosis may be explained by the slow nature of fibrogenesis or to the relatively low dose of proline that can be used.

Healthy Tissue Uptake of 68Ga-Prostate-Specific Membrane Antigen, 18F-DCFPyL, 18F-Fluoromethylcholine, and 18F-Dihydrotestosterone.

PET is increasingly used for prostate cancer (PCa) diagnostics. Important PCa radiotracers include 68Ga-prostate-specific membrane antigen HBED-CC (68Ga-PSMA), 18F-DCFPyL, 18F-fluoromethylcholine (18F-FCH), and 18F-dihydrotestosterone (18F-FDHT). Knowledge on the variability of tracer uptake in healthy tissues is important for accurate PET interpretation, because malignancy is suspected only if the uptake of a lesion contrasts with its background. Therefore, the aim of this study was to quantify uptake variability of PCa tracers in healthy tissues and identify stable reference regions for PET interpretation. Methods: A total of 232 PCa PET/CT scans from multiple hospitals was analyzed, including 87 68Ga-PSMA scans, 50 18F-DCFPyL scans, 68 18F-FCH scans, and 27 18F-FDHT scans. Tracer uptake was assessed in the blood pool, lung, liver, bone marrow, and muscle using several SUVs (SUVmax, SUVmean, SUVpeak). Variability in uptake between patients was analyzed using the coefficient of variation (COV%). For all tracers, SUV reference ranges (95th percentiles) were calculated, which could be applicable as image-based quality control for future PET acquisitions. Results: For 68Ga-PSMA, the lowest uptake variability was observed in the blood pool (COV, 19.9%), which was significantly more stable than all other tissues (COV, 29.8%-35.2%; P = 0.001-0.024). For 18F-DCFPyL, the lowest variability was observed in the blood pool and liver (COV, 14.4% and 21.7%, respectively; P = 0.001-0.003). The least variable 18F-FCH uptake was observed in the liver, blood pool, and bone marrow (COV, 16.8%-24.2%; P = 0.001-0.012). For 18F-FDHT, low uptake variability was observed in all tissues, except the lung (COV, 14.6%-23.6%; P = 0.001-0.040). The different SUV types had limited effect on variability (COVs within 3 percentage points). Conclusion: In this multicenter analysis, healthy tissues with limited uptake variability were identified, which may serve as reference regions for PCa PET interpretation. These reference regions include the blood pool for 68Ga-PSMA and 18F-DCFPyL and the liver for 18F-FCH and 18F-FDHT. Healthy tissue SUV reference ranges are presented and applicable as image-based quality control.

A method to measure the absorbed dose of the thyroid during I-131 therapy, using a collar detector system and a SPECT acquisition.

PURPOSE: Due to variations in biological half-life, accurate thyroid dosimetry for I-131 therapy is not trivial in clinical practice. In recent publications, systems are described to measure the uptake of I-131 in the thyroid repeatedly over time. In this work, we present a method to calculate patient specific pharmacokinetics and absorbed dose using such a collar detector system (CoTI) in combination with a SPECT acquisition and a two-compartment model fit. METHODS: For three patients receiving I-131 therapy for benign thyroid conditions, the complete uptake profile is measured over a period of 15 to 25 days after administration. A SPECT measurement is performed to assess the functional volume of the thyroid and the amount of I-131 in the thyroid. The uptake profile measured in counts-per-second is converted to absolute activity in MBq using the absolute quantification of the SPECT. A two-compartment model is used as a fit to the uptake data of the thyroid and to estimate the activity in the blood-pool. The estimated absorbed dose to the thyroid is then calculated from the integral of the activity. The assessed parameters from the method (6- and 24-h uptake, thyroid volume and I-131 uptake concentration) are compared with the values as determined in clinical practice. Furthermore, the convergence of the calculated absorbed dose as a function of measurement series duration is determined to assess the required measurement duration of the uptake profile. RESULTS: The two-compartment model fit shows a good agreement with the measured data points. Resulting dynamic uptake profiles of the three patients differ from each other. The uptake percentages differ from the pretherapy I-123 uptake measurements that are used in usual clinical practice, which shows the potential added value of the proposed method. The duration of the required measurement series appears to be patient dependent and therefore needs to be determined for each patient individually. The proposed method allows for a basic investigation of the individual dynamic uptake profile of I-131 in the thyroid and the calculation of the absorbed dose. CONCLUSIONS: The proposed measurement method is feasible and easily implementable given a system that can measure the uptake of I-131 in the thyroid repeatedly over time. The observed differences in dynamic uptake profiles and the differences in the absorbed thyroid dose as calculated with our method and the parameters of the usual clinical care support the relevance of the proposed method. In future studies, this approach may possibly be used for outcome prediction and therapeutic activity optimization.

Occupancy of dopamine D2 receptors by antipsychotic drugs is related to nicotine addiction in young patients with schizophrenia.

RATIONALE: Occupancy of dopamine D2 receptors by antipsychotic drugs depends on the individual availability of D2 receptors and on the dose and type of antipsychotic medication. It has been suggested that a low availability of these receptors may increase the risk for addictive behavior. OBJECTIVE: This study aims to show that patients with relatively high occupancy of D2 receptors by antipsychotic drugs are more prone to nicotine consumption. METHODS: Striatal D2 receptor occupancy by equivalent doses of olanzapine or risperidone was assessed with [123I]iodobenzamide single-photon emission computed tomography (SPECT) in 36 patients with schizophrenia. Smoking status at the time of SPECT imaging was assessed. The number of cigarettes used in the following three consecutive years was estimated with the Life Chart Schedule (LCS). RESULTS: There was a positive and significant relation between D2 receptor occupancy following treatment with olanzapine (n=19) or risperidone (n=12) and the number of cigarettes smoked in three consecutive years (r=0.60, p<0.001) in patients who smoked. There was a significant difference in the percentage of D2 occupancy for smokers (mean 74.3%, SD 12.8, n=31) and nonsmokers (mean 49.8%, SD 9.1, n=5). CONCLUSION: Frequency of cigarette smoking in schizophrenic patients treated with antipsychotic medication is significantly and negatively related to the availability of striatal D2 receptors.

GMP-compliant (68)Ga radiolabelling in a conventional small-scale radiopharmacy: a feasible approach for routine clinical use.

BACKGROUND: The number of routine care patient examinations with (68)Ga radiopharmaceuticals is still relatively limited, probably caused by the presumed need for large investments in hot cells, automated synthesis modules, laboratory equipment and validation efforts. Our aim was to set up the preparation of (68)Ga-DOTA-NOC in compliance with all current European Union-Good Manufacturing Practices (EU-GMP), current Good Radiopharmacy Practice (cGRPP) and European Pharmacopoeia (Ph. Eur.) guidance but without the availability of a hot cell and gas chromatography (GC), high-performance liquid chromatography (HPLC) and atomic absorption spectrometry (AAS) equipment. METHODS: A risk-based approach was applied to align preparation conditions with applicable regulations, together with a validation of a thin-layer chromatography (ITLC) method to replace HPLC as modality for examining radiochemical purity. RESULTS: Using an internally shielded labelling module for manual operation, a (68)Ga-DOTA-NOC labelling procedure was set up that meets all applicable Ph. Eur. specifications. The applied ITLC method showed very good correlation with HPLC results (r = 0.961) and was able to detect relevant deviations in radiolabelling procedures. All identified quality assurance aspects were made compliant with EU-GMP and cGRPP guidance. CONCLUSIONS: We consider the described configuration and validation approach feasible for many conventional small-scale radiopharmacies, something that could help to increase the availability of (68)Ga radiopharmaceuticals to a large number of patients.