Diagnostic accuracy of anti-3-[18F]-FACBC PET/MRI in gliomas.

PURPOSE: 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. METHODS: 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. RESULTS: 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% (95%CI [45, 77]) and 72% (95%CI [58, 87]), respectively, in the detection of gliomas. Median TBRpeak was 7.1 (range: 1.4-19.2) for PET positive tumors. All CNS WHO grade 1 pilocytic astrocytomas/gangliogliomas, grade 3 oligodendrogliomas, and grade 4 glioblastomas/astrocytomas were PET positive, while 25% of grade 2-3 astrocytomas and 56% of grade 2-3 oligodendrogliomas were PET positive. Generally, TBRpeak increased with malignancy grade for diffuse gliomas. A significant difference in PET uptake between CNS WHO grade 2 and 4 gliomas (p < 0.001) and between grade 3 and 4 gliomas (p = 0.002) was observed. Diffuse IDH wildtype gliomas had significantly higher TBRpeak compared to IDH1/2 mutated gliomas (p < 0.001). Adding anti-3-[18F]FACBC PET to MRI improved the accuracy of predicted glioma grades, types, and IDH status, and yielded 13.9 and 16.7 percentage point improvement in the overall diagnoses for both readers, respectively. CONCLUSION: Anti-3-[18F]FACBC PET demonstrated high uptake in the majority of gliomas, especially in IDH wildtype gliomas, and improved the accuracy of preoperatively predicted glioma diagnoses. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04111588, URL: https://clinicaltrials.gov/study/NCT04111588.

Glioblastoma PET/MRI: kinetic investigation of [18F]rhPSMA-7.3, [18F]FET and [18F]fluciclovine in an orthotopic mouse model of cancer.

PURPOSE: 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). METHODS: [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. RESULTS: [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). CONCLUSION: [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.

Prognostic value of combined MTV and ADC derived from baseline FDG PET/MRI in aggressive non-Hodgkins lymphoma.

PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[18F]Fluciclovine PET/CT: joint EANM and SNMMI procedure guideline for prostate cancer imaging-version 1.0.

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.

Simple dichotomous assessment of cranial artery inflammation by conventional 18F-FDG PET/CT shows high accuracy for the diagnosis of giant cell arteritis: a case-control study.

PURPOSE: To estimate the diagnostic accuracy of conventional 18F-FDG PET/CT of cranial arteries in the diagnosis of giant cell arteritis (GCA). METHODS: The study was a retrospective case-control study. The reference diagnosis was fulfillment of the 1990 ACR criteria for GCA. All patients had new-onset GCA. Conventional 18F-FDG PET/CT was performed before glucocorticoid treatment. Controls were age- and sex-matched patients with a previous history of malignant melanoma (MM) undergoing surveillance PET/CT >6 months after MM resection. PET images were evenly cropped to include only head and neck and were assessed in random order by four nuclear medicine physicians blinded to reference diagnosis. Temporal (TA), maxillary (MA) and vertebral (VA) arteries were visually rated for 18F-FDG uptake. Interreader agreement was evaluated by Fleiss kappa. RESULTS: A total of 44 patients and 44 controls were identified. In both groups, the mean age was 69 years (p = 0.45) and 25/44 were women. 35/41 GCA patients were temporal artery biopsy positive (TAB). Considering only FDG uptake in TA and/or MA, diagnostic sensitivity and specificity was 64 and 100%. Including VA, sensitivity increased to 82% and specificity remained 100%. Interreader agreement was 91% and Fleiss kappa 0.82 for the PET diagnosis based on the cranial arteries. CONCLUSION: Conventional 18F-FDG PET/CT is an accurate and reliable tool to diagnose cranial arteritis in glucocorticoid-naïve GCA patients. The high diagnostic specificity suggests that TAB can be omitted in patients with 18F-FDG uptake in cranial arteries. 18F-FDG PET/CT performed in patients with suspected vasculitis should always include the head and neck.

Sequential intranodal immunotherapy induces antitumor immunity and correlated regression of disseminated follicular lymphoma.

Advanced stage follicular lymphoma (FL) is incurable by conventional therapies. In the present pilot clinical trial, we explored the efficacy and immunogenicity of a novel in situ immunotherapeutic strategy. Fourteen patients with untreated or relapsed stage III/IV FL were included and received local radiotherapy to solitary lymphoma nodes and intranodal injections of low-dose rituximab (5 mg), immature autologous dendritic cells, and granulocyte-macrophage colony-stimulating factor at the same site. The treatment was repeated 3 times targeting different lymphoma nodes. Primary end points were clinical responses and induction of systemic immunity. Five out of 14 patients (36%) displayed objective clinical responses, including 1 patient with cutaneous FL who showed regression of skin lesions. Two of the patients had durable complete remissions. Notably, the magnitude of vaccination-induced systemic CD8 T-cell-mediated responses correlated closely with reduction in total tumor area (r = 0.71, P = .006), and immune responders showed prolonged time to next treatment. Clinical responders did not have a lower tumor burden than nonresponders pretreatment, suggesting that the T cells could eliminate large tumor masses once immune responses were induced. In conclusion, the combined use of 3 treatment modalities, and in situ administration in single lymphoma nodes, mediated systemic T-cell immunity accompanied by regression of disseminated FL. The trial was registered at www.clinicaltrials.gov as #NCT01926639.

Nordic MCL3 study: 90Y-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma.

The main objective of the MCL3 study was to improve outcome for patients not in complete remission (CR) before transplant by adding (90)Y-ibritumomab-tiuxetan (Zevalin) to the high-dose regimen. One hundred sixty untreated, stage II-IV mantle cell lymphoma patients <66 years received rituximab (R)-maxi-CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) alternating with R-high-dose cytarabine (6 cycles total), followed by high-dose BEAM/C (bis-chloroethylnitrosourea, etoposide, cytarabine, and melphalan or cyclophosphamide) and autologous stem cell transplantation from 2005 to 2009. Zevalin (0.4 mCi/kg) was given to responders not in CR before transplant. Overall response rate pretransplant was 97%. The outcome did not differ from that of the historic control: the MCL2 trial with similar treatment except for Zevalin. Overall survival (OS), event-free survival (EFS), and progression-free survival (PFS) at 4 years were 78%, 62%, and 71%, respectively. For responding non-CR patients who received Zevalin, duration of response was shorter than for the CR group. Inferior PFS, EFS, and OS were predicted by positron emission tomography (PET) positivity pretransplant and detectable minimal residual disease (MRD) after transplant. In conclusion, positive PET and MRD were strong predictors of outcome. Intensification with Zevalin may be too late to improve the outcome of patients not in CR before transplant. This trial was registered at www.clinicaltrials.gov as #NCT00514475.

An implementation of time-efficient respiratory-gated PET acquisition by repeated breath-holds.

BACKGROUND: Respiratory gating in positron emission tomography (PET) is used to improve detection of small tumors in the lower lung regions and in the liver, and to obtain a better estimate of the standardized uptake value (SUV). PURPOSE: To develop a time-efficient method for acquisition of respiratory-gated PET/CT that would produce one single high quality image volume corresponding to a breath-hold state. MATERIAL AND METHODS: An instrument was developed that displayed to the patient either red or green numbers, counting down from a chosen maximum to one at a rate of one dial per second. The patient was instructed to repeatedly hold the breath in moderate inspiration when red numbers were displayed and to breathe freely during display of green numbers. PET data were acquired in list mode and trigger signals were sent to the scanner and inserted into the list file each time the color of the countdown numbers switched from green to red. Data acquired during breath-holds were used to create one single image volume. RESULTS: High quality breath-hold images were obtained from 10 min data acquisition at one bed position. Improved image quality compared to standard whole-body PET was demonstrated by a significant reduction of noise (standard deviation) in regions of normal liver tissues. CONCLUSION: The instruction to perform repeated breath-holds was well understood by patients and they cooperated satisfactorily. When the new procedure is used the duration of the data acquisition may typically be reduced by a factor of 4 compared to conventional respiratory-gated protocols where the patient breathes freely.

Effect of Androgen Deprivation Therapy on the Results of PET/CT with 18F-Fluciclovine in Patients with Metastatic Prostate Cancer.

Background: 18F-fluciclovine is a positron emission tomography (PET) radiotracer approved for the detection of prostate cancer recurrence. No effect of androgen deprivation therapy (ADT) on its performance has been established. Purpose: To study the impact of concurrent ADT on disease detection with 18F-fluciclovine PET in patients with prostate cancer. Materials and Methods: Data from patients with prostate cancer who had been receiving ADT for ≥3 months at the time of undergoing an 18F-fluciclovine PET/CT at our institution were retrospectively reviewed. Seventy-three scans from 71 patients were included. The scans indicated rising prostate-specific antigen (n = 58), staging advanced disease (n = 4) or therapeutic monitoring (n = 9). Patients' medical records provided baseline clinical data and post-scan outcomes (median follow-up 40 months). Results: Malignant lesions with increased uptake of 18F-fluciclovine were detected in 60/73 (82%) scans; 33 (45%) had lesions in the prostate/bed and 46 (63%) in extraprostatic sites. Patients received ADT for a median of 2 years (range 3 months to >10 years) pre-scan. The time on ADT did not influence detection; the detection rates were 89% for patients who had received ADT for <1 year, 63% for a treatment period of 1−<2 years, 83% for 2−4 years, 78% for >4−10 years, and 67% for a treatment period of >10 years. Conclusion: 18F-fluciclovine detected recurrent or metastatic lesions in 82% of patients with prostate cancer receiving ADT. The rates achieved in the present study are consistent with widely reported data for 18F-fluciclovine PET/CT, suggesting that withdrawal of ADT before scanning is not necessary.

Diagnostic Value of 18 F-FACBC PET/MRI in Brain Metastases.

PURPOSE: The study aims to evaluate whether combined 18 F-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 18 F-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; SUV max , 1.2-8.4; TBR, 3.9-25.9), whereas 10/29 lesions were undetected (D max MR , ≤8 mm; SUV max , 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; SUV max , 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: 18 F-FACBC PET demonstrated uptake in brain metastases from cancer of different origins (lung, gastrointestinal tract, breast, thyroid, and malignant melanoma). However, 18 F-FACBC PET/MRI did not improve detection of brain metastases compared with MRI but might detect tumor tissue beyond contrast enhancement on MRI. 18 F-FACBC PET should be further evaluated in recurrent brain metastases.

The prognostic role of 18F-fluorodeoxyglucose PET in head and neck cancer depends on HPV status.

BACKGROUND AND PURPOSE: Standardized uptake value (SUV) and related parameters derived from 2-deoxy-2-[18F]-fluoro-d-glucose (FDG) PET/CT prior to radiochemotherapy of head and neck cancer (HNC) were significantly associated with survival in a number of studies. The aim of this study was to validate these findings and to evaluate the prognostic role of PET parameters also including clinical factors and HPV status. MATERIALS AND METHODS: We reviewed 166 HNC cases with a radiotherapy planning FDG PET/CT scan. All patients received radiotherapy, 68-70 Gy with or without concomitant cisplatin. Primary endpoint was disease-free survival (DFS). Twelve clinical factors, including HPV, performance status, stage and treatment parameters and ten PET/CT image parameters including gross tumor volume (GTV), metastatic lymph node volume, SUVmax, metabolic tumor volume (MTV) and total lesion glycolysis (TLG), were collected. Univariate and multivariate Cox regression analyses were employed. RESULTS: Of the 166 patients included, 48 had locoregional and 23 had metastatic recurrence. None of the FDG PET parameters were significant in the univariate analysis using DFS as endpoint. HPV status, ECOG status and GTV-U (primary tumor and lymph node volume from CT) were statistically significant (p < 0.01). Only in the subgroup of HPV-unrelated HNC (HPV negative oropharyngeal cancer [OPC] and non-OPC; n = 73), the multivariate model could be improved by including MTV (p < 0.001). DFS events were 29 (31%) in HPV-related and 53 (73%) in HPV-unrelated HNC. CONCLUSION: FDG PET parameters appear less important for overall prognostication of radiochemotherapy outcome for HNC. Still, the association between the FDG PET parameters and survival is strong for HNC not related to HPV. Tumor volume from CT is generally more closely related to outcome than parameters derived from FDG PET/CT.

A comparative study of standardized quantitative and visual assessment for predicting tumor volume and outcome in newly diagnosed diffuse large B-cell lymphoma staged with 18F-FDG PET/CT.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

18F-FDG PET in the management of patients with anaplastic thyroid carcinoma.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive solid tumors in humans. The use of positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) in ATC has not been studied, and only a few case reports have been published. The objective of this study was to investigate the potential contribution of 18F-FDG PET to the clinical management of patients with ATC. METHODS: All patients with ATC studied with 18F-FDG PET from August 2001 through March 2007 were included. The PET results were correlated with computed tomography, ultrasound, magnetic resonance imaging, bone scan, histology, and clinical follow-up. The FDG uptake was semiquantified as maximum standard uptake value. Any change in the treatment plan as a direct result of the PET findings as documented in the clinical notes was recorded. RESULTS: Sixteen patients were included. True-positive PET findings were seen for all primary tumors, in all nine patients with lymph node metastases, in five out of eight patients with lung metastases, and in two patients with distant metastases other than lung metastases. In 8 of the 16 patients, the medical records reported a direct impact of the PET findings on the clinical management. CONCLUSIONS: ATC demonstrates intense uptake on 18F-FDG PET images. In 8 of the 16 patients (50%), the medical records reported a direct impact of the PET findings on the management of the patient. PET may improve disease detection and have an impact on the management of patients with ATC relative to other imaging modalities.

Optimal 2-[(18)F]fluoro-2-deoxy-D-galactose PET/CT protocol for detection of hepatocellular carcinoma.

BACKGROUND: Positron emission tomography (PET) with the liver-specific galactose tracer 2-[(18)F]fluoro-2-deoxy-D-galactose ((18)F-FDGal) may improve diagnosis of hepatocellular carcinoma (HCC). The aim of this study was to test which of three different (18)F-FDGal PET protocols gives the highest tumour-to-background (T/B) ratio on PET images and thus better detection of HCC tumours. METHODS: Ten patients with a total of 15 hepatic HCC tumours were enrolled prior to treatment. An experienced radiologist defined volumes of interest (VOIs) encircling HCC tumours on contrast-enhanced CT (ce-CT) images. Three PET/CT protocols were conducted following an intravenous (18)F-FDGal injection: (i) a 20-min dynamic PET/CT of the liver (to generate a 3D metabolic image), (ii) a traditional static whole-body PET/CT after 1 h, and (iii) a late static whole-body PET/CT after 2 or 3 h. PET images from each PET/CT protocol were fused with ce-CT images, and the average standardized uptake values (SUV) in tumour and background liver tissue were used to calculate (T/B) ratios. Furthermore, Tpeak/B ratios were calculated using the five hottest voxels in all hot tumours. The ratios for the three different PET protocols were compared. RESULTS: For the individual tumours, there was no significant difference in the T/B ratio between the three PET protocols. The metabolic image yielded higher Tpeak/B ratios than the two static images, but it was easier to identify tumours on the static images. One extrahepatic metastasis was detected. CONCLUSIONS: Neither metabolic images nor static whole-body images acquired 2 or 3 h after (18)F-FDGal injection offered an advantage to traditional whole-body PET/CT images acquired after 1 h for detection of HCC.

Changes in prostate-specific antigen, markers of bone metabolism and bone scans after treatment with radium-223.

OBJECTIVE: The aim of this study was to assess treatment-related changes in prostate-specific antigen (PSA), total and bone alkaline phosphatase (total ALP, bone ALP), and changes on conventional bone scans in patients with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases who received six cycles of radium-223 (Ra-223). MATERIALS AND METHODS: Changes in PSA, total ALP and bone ALP (≥30% increase or decrease), and changes on bone scans were assessed before and after six monthly cycles of Ra-223 therapy (50 kBq/kg body weight) in 14 patients with mCRPC with bone metastases and four patients on placebo. RESULTS: Post-treatment PSA increased by at least 30% in 11 out of 14 patients and remained stable in three. Total ALP and bone ALP decreased in six and nine patients, respectively. In 10 out of 12 evaluable patients the uptake on post-treatment bone scan was reduced in lesions with high pretreatment uptake, in 11 patients accompanied by the development of new or expanded bone lesions. FACBC position emission tomography/computed tomography scans confirmed the growth of new or expanded bone metastases in two patients. CONCLUSIONS: These observations support the notion that Ra-223 kills tumour cells in metastases surrounded by highly proliferating osteoblasts, consistent with the reported survival benefit. The radiation effect in small tumour deposits not surrounded by increased osteoblast activity seems, however, insufficient, thus allowing continuous tumour growth. Long-lasting PSA reductions are the exception rather than the rule during Ra-223 treatment, whereas alkaline phosphatases decrease more frequently. To improve the overall anticancer effect, Ra-223 might be a valuable component of combination treatment.

Respiratory gated PET/CT of the liver: A novel method and its impact on the detection of colorectal liver metastases.

PURPOSE: To evaluate the diagnostic performance of a new method for respiratory gated positron emission tomography (rgPET/CT) for colorectal liver metastases (CRLM), secondly, to assess its additional value to standard PET/CT (PET/CT). MATERIALS AND METHODS: Forty-three patients scheduled for resection of suspected CRLM were prospectively included from September 2011 to January 2013. None of the patients had previously undergone treatment for their CRLM. All patients underwent PET/CT and rgPET/CT in the same session. For rgPET/CT an in-house developed electronic circuit was used which displayed a color-coded countdown for the patient. The patients held their breath according to the countdown and only the data from the inspiration breath-hold period was used for image reconstruction. Two independent and blinded readers evaluated both PET/CT and rgPET/CT separately. The reference standard was histopathological confirmation for 73 out of 131 CRLM and follow-up otherwise. RESULTS: Reference standard identified 131 CRLM in 39/43 patients. Nine patients accounted for 25 mucinous CRLM. The overall per-lesion sensitivity for detection of CRLM was for PET/CT 60.0%, for rgPET/CT 63.1%, and for standard+rgPET/CT 67.7%, respectively. Standard+rgPET/CT was overall significantly more sensitive for CRLM compared to PET/CT (p=0.002) and rgPET/CT (p=0.031). The overall positive predictive value (PPV) for detection of CRLM was for PET/CT 97.5%, for rgPET/CT 95.3%, and for standard+rgPET/CT 93.6%, respectively. CONCLUSION: Combination of PET/CT and rgPET/CT improved the sensitivity significantly for CRLM. However, high patient compliance is mandatory to achieve optimal performance and further improvements are needed to overcome these limitations. The diagnostic performance of the evaluated new method for rgPET/CT was comparable to earlier reported technically more complex and expensive methods.

[Sentinel lymph node biopsy in breast carcinoma: the experience from the Norwegian Radium Hospital]. / Biopsi av vaktpostlymfeknute ved brystkreft.

BACKGROUND: We report our experience with sentinel lymph node (SLN) biopsy in breast carcinoma. MATERIAL AND METHODS: The series included 51 women with invasive carcinoma and 3 ductal carcinoma in situ. The first 32 patients underwent axillary lymph node dissection (ALND) independently of the results of the SLN biopsy. SLN was evaluated on frozen sections, paraffin sections and with immunohistochemistry. RESULTS: The surgical detection rate was 98 % with a combined technique of radiocolloid and blue dye. Negative SLN was seen in 36 patients. ALND was done in 19 of these patients, with no metastases found in non-SLN. Metastases were found in SLN in 18 patients, in 3 patients detected only on immunohistochemistry. ALND was done in all positive cases. Three patients had positive non-SLN. INTERPRETATION: SLN biopsy seems accurate in breast carcinoma, performed with the use of radiotracer and blue dye. Immunohistochemistry increases the sensitivity of SLN biopsy.

[Positron emission tomography in the diagnosis of lung cancer]. / Positronemisjonstomografi i utredningen av lungekreftpasienter.

BACKGROUND: Lung cancer is a common malignancy. Positron emission tomography (PET) has become an important tool in the staging of the disease with regard to operability and in order to determine radiation volume when surgery is not indicated. MATERIALS AND METHODS: We have assessed and discuss results recently published in major international journals. RESULTS: In approximately 60% of the patients, the planning of treatment is modified after a PET investigation. INTERPRETATION: In contrast to the state the art in most industrialised countries, dedicated PET is not available in Norway. Hence lung cancer is suboptimally treated.