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PURPOSE: Despite improved treatment options, multiple myeloma (MM) remains an incurable disease. The aim of this study was to investigate the prognostic value of positron emission tomography/computed tomography (PET/CT) using 18F-2'-deoxy-2'-fluorodeoxyglucose ([18F]FDG) in MM patients shortly before and ~100 days after allogeneic hematopoietic cell transplantation (allo-HCT). METHODS: In this retrospective analysis, we evaluated [18F]FDG-PET/CT-scans of 45 heavily pre-treated MM patients before and 27 patients after scheduled allo-HCT. All scans were qualitatively and semi-quantitatively assessed for the presence of active disease. Serological response was recorded according to International Myeloma Working Group (IMWG) criteria. Progression-free (PFS) and overall survival (OS) were correlated with different PET/CT-derived parameters, such as presence, number and maximum standardized uptake value (SUVmax) of focal myeloma lesions. The impact of extramedullary disease on patient outcome was also assessed. RESULTS: PET/CT negativity -prior to or following allo-HCT- was a favorable prognostic factor for progression-free and overall survival (both, PFS and OS: pre-HSCT p < 0.001, post-HCT p < 0.005). High FDG-uptake (SUVmax > 6.5) revealed a significantly shortened survival compared to patients with a lower SUVmax (<6.5) (OS, 5.0 ± 1.1 m vs. not reached - longest 122.0 m; p < 0.001). Moreover, our data prove that a higher number (>3) of focal lesions (pre-HCT: both PFS and OS: p < 0.001; post-HCT PFS: p < 0.001, OS: p = 0.139) as well as the presence of extramedullary disease serve as adverse prognostic factors prior to and after allo-HCT. At response assessment after allo-HCT, [18F]FDG-PET/CT had a complementary value in prognostication in addition to IMWG criteria alone. CONCLUSION: [18F]FDG-PET/CT before and shortly after allogeneic HCT is a powerful predictor for progression-free and overall survival in MM patients.

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AIM: Recently, [F]tetrafluoroborate ([F]TFB) has been introduced as a versatile PET probe for imaging the human sodium/iodide symporter activity. This pilot study aimed to compare [F]TFB-PET/CT with [I]NaI-PET/CT imaging in thyroid cancer patients. METHODS: Nine patients with newly diagnosed differentiated thyroid cancer underwent both [F]TFB- and [I]NaI-PET/CT after total thyroidectomy. PET/CT scans were visually analyzed for the presence of remnant thyroid tissue and for metastatic lesions on a patient and lesion basis. For semiquantitative analysis, thyroid remnant/tumor to blood pool ratios were calculated. RESULTS: All patients presented with positive [F]TFB and [I]NaI-PET/CT scans. Retention of I in remnant thyroid tissue was significantly higher as compared with [F]TFB (P < 0.01). In a lesion-based analysis, both tracers identified an almost equal number of foci with [F]TFB depicting a total of 41 foci and I a total of 40 foci, respectively. In 6 of 9 patients, both radiopharmaceuticals returned an identical number of foci. Two I-positive benign thyroid remnants were missed by [F]TFB-PET/CT in a single patient. In another case, both tracers identified different thyroid remnant tissues in the cervical region. Notably, [F]TFB demonstrated additional (I-negative) cervical lymph node metastases in 2 patients, leading to an overall agreement between the radiotracers of 91% (74/81 foci). DISCUSSION: In this pilot study, [F]TFB-PET was not inferior to [I]NaI-PET for detecting thyroid cancer and its metastases and was able to detect [I]NaI-PET-negative viable differentiated thyroid cancer metastases. Further clinical evaluation as a PET tracer for imaging thyroid pathophysiology and human sodium/iodide symporter expressing neoplasms is highly warranted.

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Therapeutic options in advanced medullary thyroid carcinoma (MTC) have markedly improved since the introduction of tyrosine kinase inhibitors (TKIs). We aimed to assess the role of metabolic imaging using 18F-FDG PET/CT shortly before and 3 mo after initiation of TKI treatment. Methods: Eighteen patients with advanced and progressive MTC scheduled for vandetanib treatment underwent baseline 18F-FDG PET/CT before and 3 mo after TKI treatment initiation. During follow-up, CT scans were obtained every 3 mo and analyzed according to RECIST. The predictive value for estimating progression-free survival (PFS) and overall survival (OS) was examined by investigating the 18F-FDG SUVmean/max of the metabolically most active lesion, as well as by analyzing clinical parameters (tumor marker doubling times [calcitonin, carcinoembryonic antigen], prior therapies, rearranged-during-transfection mutational status, and disease type). Results: Within a median follow-up of 5.2 y, 9 patients experienced disease progression after a median interval of 2.1 y, whereas the remainder had ongoing disease control (5 with a partial response and 4 with stable disease). Eight of the 9 patients with progressive disease died from MTC after a median of 3.5 y after TKI initiation. A pretherapeutic SUVmean of more than 4.0 predicted a significantly shorter PFS (1.9 y vs. 5.2 y, P = 0.04). Furthermore, sustained high 18F-FDG uptake at 3 mo with a SUVmean of more than 2.8 tended to portend an unfavorable prognosis, with a PFS of 1.9 y (vs. 3.5 y, P = 0.3). Prolonged carcinoembryonic antigen doubling times were significantly correlated with longer PFS (r = 0.7) and OS (r = 0.76, P < 0.01). None of the other clinical parameters had prognostic significance. Conclusion: Pretherapeutic 18F-FDG PET/CT provides prognostic information in patients with advanced MTC scheduled for treatment with the TKI vandetanib. A low tumor metabolism with an SUVmean of less than 4.0 before treatment predicts a longer PFS.

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11C-methionine (MET) has recently emerged as an accurate marker of tumor burden and disease activity in patients with multiple myeloma (MM). This dual-center study aimed at further corroboration of the superiority of MET as positron emission tomography (PET) tracer for staging and re-staging MM, as compared to 18F-2`-deoxy-2`-fluoro-D-glucose (FDG). 78 patients with a history of solitary plasmacytoma (n=4), smoldering MM (SMM, n=5), and symptomatic MM (n=69) underwent both MET- and FDG-PET/computed tomography (CT) at the University Centers of Würzburg, Germany and Navarra, Spain. Scans were compared on a patient and on a lesion basis. Inter-reader agreement was also evaluated. In 2 patients, tumor biopsies for verification of discordant imaging results were available. MET-PET detected focal lesions (FL) in 59/78 subjects (75.6%), whereas FDG-PET/CT showed lesions in only 47 patients (60.3%; p<0.01), accordingly disease activity would have been missed in 12 patients. Directed biopsies of discordant results confirmed MET-PET/CT results in both cases. MET depicted more FL in 44 patients (56.4%; p<0.01), whereas in two patients (2/78), FDG proved superior. In the remainder (41.0%, 32/78), both tracers yielded comparable results. Inter-reader agreement for MET was higher than for FDG (κ = 0.82 vs κ = 0.72). This study demonstrates higher sensitivity of MET in comparison to standard FDG to detect intra- and extramedullary MM including histologic evidence of FDG-negative, viable disease exclusively detectable by MET-PET/CT. MET holds the potential to replace FDG as functional imaging standard for staging and re-staging of MM.

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PURPOSE: Radioguided sentinel lymph node biopsy (SLNB) is the standard of care in breast cancer and melanoma. Additional preoperative Single-photon emission computed tomography (SPECT/CT) for improved anatomical co-registration of the SLNs causes additional radiation exposure and is time-consuming and expensive. The aim of this prospective study was to evaluate a novel approach involving real-time fusion of freehand SPECT (fhSPECT) and ultrasound (US) for anatomical co-registration of SLNs. METHODS: From February 2015 to February 2016, 153 patients were included in this prospective study. All patients underwent lymphoscintigraphy according to practical guidelines and 151 (118 cases of breast cancer, 30 cutaneous malignancies, and three cases of vulvar cancer) of the 153 patients were additionally investigated with fhSPECT-US. FhSPECT connected to a hand-held gamma detector generates three-dimensional images of the radioactivity distribution in the scanned area. For co-registration and real-time fusion of fhSPECT and subsequently performed US, an infrared stereo tracking system was used. RESULTS: In all patients an SLN was found on lymphoscintigraphy, and the fhSPECT detected corresponding hotspots in all but one patient. In 72 % of patients and 73 % of lymph node basins, real-time anatomical co-registration with US was feasible. The rate of success in achieving good co-registration increased from 60 to 75 % after training by a radiologist specialized in breast imaging. A higher co-registration rate (78 %) was observed in patients with only one SLN than in those with two SLNs (68 %) or three or more SLNs (0 %). CONCLUSIONS: Real-time fusion of fhSPECT and US for preoperative anatomical co-registration of SLNs is feasible. However, before this approach can completely replace preoperative lymphatic imaging, further technical developments are needed.

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Diagnosis of recurrent hepatocellular carcinoma (HCC) is sometimes challenging, especially when extrahepatic disease is present. Here, we report on a 49-year-old woman with a history of HCC who was referred to our institution with suspicion of tumor recurrence for further workup. Combined F-choline PET/CT revealed a soft tissue mass at the right thoracic wall highly consistent with HCC.

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Chemokine receptor CXCR4 is a key factor for tumor growth and metastasis in several types of human cancer. This study investigated the feasibility of CXCR4-directed imaging of small cell lung cancer (SCLC) with positron emission tomography/computed tomography (PET/CT) using the radiolabelled chemokine ligand [68Ga]Pentixafor. 10 patients with primarily diagnosed (n=3) or pre-treated (n=7) SCLC (n=9) or large cell neuroendocrine carcinoma of the lung (LCNEC, n=1) underwent [68Ga]Pentixafor-PET/CT. 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG, n=6) and/or somatostatin receptor (SSTR)-directed PET/CT with [68Ga]DOTATOC (n=5) and immunohistochemistry (n=10) served as standards of reference. CXCR4-PET was positive in 8/10 patients and revealed more lesions with significantly higher tumor-to-background ratios than SSTR-PET. Two patients who were positive on [18F]FDG-PET were missed by CXCR4-PET, in the remainder [68Ga]Pentixafor detected an equal (n=2) or higher (n=2) number of lesions. CXCR4 expression of tumor lesions could be confirmed by immunohistochemistry. Non-invasive imaging of CXCR4 expression in SCLC is feasible. [68Ga]Pentixafor as a novel PET tracer might serve as readout for confirmation of CXCR4 expression as prerequisite for potential CXCR4-directed treatment including receptor-radio(drug)peptide therapy.

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INTRODUCTION: Peptide receptor radionuclide therapy (PRRT) is a treatment option for both iodine-refractory differentiated and advanced medullary thyroid cancer (TC). It requires over-expression of somatostatin receptor subtype II (SSTR) that can be non-invasively assessed by positron emission tomography (PET). Assessment of tumor heterogeneity is increasingly used as a tool for prognostication prediction. We investigated the potential of SSTR-PET to assess intraindividual tumor heterogeneity and thereby treatment response prior to PRRT. METHODS: 12 patients with progressive radioiodine-refractory differentiated (1 papillary, 1 oxyphilic, 2 oncocytic, 4 follicular) or medullary (n=4) TC were enrolled. SSTR-PET was performed at baseline. Conventional PET parameters and heterogeneity parameters were analyzed regarding their potential to predict progression-free (PFS, mean, 221 days) and overall survival (OS, mean, 450 days). Parameters of a subgroup of lesions (n=23) were also correlated with morphological response according to modified RECIST criteria. RESULTS: In patient-based analysis, all conventional parameters failed to predict PFS. Several textural parameters showed a significant capability to assess PFS. Thereby, "Grey level non uniformity" had the highest area under the curve (AUC, 0.93) in Receiver operating characteristics analysis followed by "Contrast" (AUC, 0.89). In lesion-based analysis, only "Entropy" revealed potential to evaluate disease progression. OS could not be assessed by any parameter investigated. CONCLUSIONS: Tumor heterogeneity seems to be a predictor of response to PRRT in patients with iodine-refractory differentiated/advanced medullary thyroid cancer and outperforms conventional PET parameters like standardized uptake value. In a "theranostic" approach, assessment of textural parameters may help in selecting patients who might benefit from PRRT.

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