Repeated adjuvant anti-CEA radioimmunotherapy after resection of colorectal liver metastases: Safety, feasibility, and long-term efficacy results of a prospective phase 2 study.

BACKGROUND: In previous work, a single administration of anticarcinoembryonic antigen (anti-CEA) 131 I-labetuzumab radioimmunotherapy (RIT) after complete resection of colorectal liver metastases was well tolerated and significantly improved survival compared with controls. In the current phase 2 trial, the authors studied repeated RIT in the same setting, examining safety, feasibility, and efficacy. METHODS: Sixty-three patients (median age, 64.5 years) received RIT at 40 to 50 millicuries/m2 per dose. Before the receipt of RIT, restaging was performed with computed tomography/magnetic resonance imaging and 18 F-fluorodeoxyglucose-positron emission to confirm that patients were "truly adjuvant." Patients who had elevated serum CEA levels or radiographically inconclusive new lesions were classified as "possibly nonadjuvant," but they also received RIT. Time to progression (TTP), overall survival (OS), and cause-specific survival (CSS) were calculated. The median follow-up was 54 months. RESULTS: After the first course of RIT, 14 of 63 patients experienced National Cancer Institute Common Toxicity Criteria grade 4 hematotoxicity; 19 patients did not receive the second course of RIT because of impaired performance status (N = 5) or relapse (N = 14). After the second course of RIT, 9 of 44 patients experienced National Cancer Institute Common Toxicity Criteria grade 4 hematotoxicity. Five patients developed myelodysplastic syndrome (MDS) from 22 to 55 months after their last RIT. The median TTP, OS, and CSS for all patients were 16, 55, and 60 months, respectively. The "truly adjuvant" patients (N = 39) had an improved median TTP (not reached vs 6.1 months; hazard ratio, 0.12; P < .001), OS (75.6 vs 33.4 months; hazard ratio, 0.44; P = .014), and CSS (not reached vs 41.4 months; hazard ratio,0.42; P = .014) compared with "possibly nonadjuvant" patients (N = 24). CONCLUSIONS: Repeated RIT with 131 I-labetuzumab is feasible but is associated with hematotoxicity. Survival is very encouraging, especially for "truly adjuvant" patients. However, the maximum safe dose of 131 I-labetuzumab is a single administration of 50 millicuries/m2 . Cancer 2017;123:638-649. © 2016 American Cancer Society.

Individualized treatment of differentiated thyroid cancer: The value of surgery in combination with radioiodine imaging and therapy - A German position paper from Surgery and Nuclear Medicine. / Individualisierte Behandlung von differenziertem Schilddrüsenkrebs: Der Wert der Operation in Kombination mit Radiojodbildgebung und -therapie ­ Ein deutsches Positionspapier aus der Chirurgie und Nuklearmedizin.

A consensus statement about indications for post-surgical radioiodine therapy (RIT) in differentiated thyroid cancer patients (DTC) was recently published by the European Thyroid Association (ETA) 1. This publication discusses indications for RIT on the basis of an individual risk assessment. Many of the conclusions of this consensus statement are well founded and accepted across the disciplines involved. However, especially from the perspective of nuclear medicine, as the discipline responsible for indicating and executing RIT, some of the recommendations may require further clarification with regard to their compatibility with established best practice and national standards of care. Assessment of the indications for RIT is strongly dependent on the weighing up of benefits and risks. On the basis of longstanding clinical experience in nuclear medicine, RIT represents a highly specific precision medicine procedure of proven efficacy with a favorable side-effect profile. This distinguishes RIT significantly from other adjuvant oncological therapies and has resulted in the establishment of this procedure as a usually well-tolerated, standard safety measure. With regard to its favorable risk/benefit ratio, this procedure should not be unnecessarily restricted, in the interest of offering reassurance to the patients. Both patients' interests and regional/national differences need to be taken into account. We would therefore like to comment on the recent consensus from the perspective of authors and to provide recommendations based on the respective published data.

99mTc-Besilesomab-SPECT/CT in Infectious Endocarditis: Upgrade of a Forgotten Method?

Infective endocarditis displays a serious condition with high mortality rates. Establishing a reliable diagnosis can be challenging. This study evaluates granulocyte imaging with 99mTc-Besilesomab-SPECT/CT in order to determine the clinical value of the method and its possible redefinition through the addition of hybrid imaging. The study comprises 26 consecutive patients with suspected infectious endocarditis or prosthetic valve infection that underwent 99mTc-Besilesomab-SPECT/CT in our facility between December 2016 and September 2018. 99mTc-Besilesomab-SPECT/CT images were reviewed by two independent and blinded observers and results were evaluated by transesophageal echocardiography (TEE) and blood culture results as well as by pathological, bacteriological, and clinical findings. Target-to-Background-Ratios were calculated for semi-quantitative analysis. 13/26 patients were in a post-surgical stage. 99mTc-Besilesomab-SPECT/CT was positive in 6 cases. All 6 cases were true positive confirmed by pathological or clinical findings according to the modified Duke Criteria for infective endocarditis. Remaining 19/26 cases were true negative. Target-to-Background ratios were significantly higher in patients that were visually scored positive compared to negative cases. Inter-observer agreement was very good of deciding whether a scan was positive or negative. Sensitivity of 99mTc-Besilesomab-SPECT/CT was 86-100% and specificity was 100%. 99mTc-Besilesomab-SPECT/CT is a useful imaging method for the diagnosis of endocarditis, especially in difficult cases with prosthetic valves or cardiac devices and inconclusive findings in echocardiography. The added value of SPECT/CT was mainly finding and localizing increased uptake at a certain valve, prosthesis, or device cable.

68Ga-Pentixafor PET/CT Imaging of Chemokine Receptor CXCR4 in Chronic Infection of the Bone: First Insights.

Because of its role in infection and inflammatory processes, the chemokine receptor CXCR4 might be a potent target in imaging of infectious and inflammatory diseases. The aim of this pilot study was to determine whether the CXCR4 ligand 68Ga-pentixafor is suitable for imaging chronic infection of the bone. Methods: The study comprised 14 patients with suspected infection of the skeleton who underwent 68Ga-pentixafor PET/CT between April 2015 and February 2017 in our facility. 68Ga-pentixafor PET/CT results were retrospectively evaluated against a histologic, bacteriologic, and clinical standard. The results were also compared with available bone scintigraphy, white blood cell scintigraphy, and 18F-FDG PET/CT results. Results:68Ga-pentixafor PET/CT was positive in 9 of 14 patients. Diagnoses included osteitis or osteomyelitis of peripheral bone, osteomyelitis of the maxilla, and infected endoprostheses. Target-to-background ratios were 5.1-15 (mean, 8.7). Eight of 9 cases were true-positive as confirmed by pathology, bacteriology, or clinical observation. All negative cases were confirmed as true-negative by other imaging modalities and follow-up. Conclusion: Imaging of CXCR4 expression with 68Ga-pentixafor PET/CT appears suitable for diagnosing chronic infection of the skeleton. The findings of this study reveal a possible diagnostic gain in suspected chronic infections that are difficult to diagnose by other imaging modalities.

Immunohistochemical detection of chemokine receptor 4 expression in chronic osteomyelitis confirms specific uptake in 68Ga-Pentixafor-PET/CT.

Previous findings of our group showed the chemokine receptor CXCR4 as a suitable target in PET/CT-imaging of axial bone infections, early postoperative osteomyelitis and periprosthetic infections. The aim of this study was to verify specific uptake of 68Ga-Pentixafor in chronic osteomyelitis. METHODS: 29 consecutive patients who underwent 68Ga-Pentixafor-PET/CT with clinically suspected osteomyelitis were evaluated retrospectively. Bone tissues of 6 patients were available and evaluated by immunohistochemical staining for CXCR4 and autoradiography with 68Ga-Pentixafor. Staining was performed with an anti-CXCR4 antibody. In order to detect lymphocytic infiltration and CXCR4-expressing lymphocytes double immunofluorescence with an anti-CD3 and anti-CXCR4 antibody was performed. RESULTS: 68Ga-Pentixafor-PET/ CT was true positive in 16 and true negative in 13 patients. In available bone tissue samples, immunohistochemical staining of CXCR4 expression and autoradiography with 68Ga-Pentixafor was highly positive. Double immunofluorescence was able to detect CXCR4-expressing T-lymphocytes within all bone samples while a control sample of noninfected tibial bone was negative for CXCR4. CONCLUSION: 68Ga-Pentixafor-PET/CT specifically shows CXCR4-expressing immune cells in chronic osteomyelitis and is therefore a suitable method for imaging chronic infection of the skeleton.Der Chemokinrezeptor CXCR4 konnte in einer Pilotstudie unserer Arbeitsgruppe als geeignete Zielstruktur zur PET/CT-Bildgebung von frühen postoperativen und periprothetischen Osteomyelitiden sowie Osteomyelitiden im Stammskelett identifiziert werden. In dieser Studie haben wir untersucht, ob 68Ga-Pentixafor spezifisch CXCR4-exprimierende Entzündungszellen in einer chronischen Osteomyelitis darstellen kann. METHODEN: Es erfolgte eine retrospektive Auswertung von 29 Patienten mit klinischem Verdacht einer chronischen Osteomyelitis, die mittels 68Ga-Pentixafor-PET/CT untersucht wurden. Hiervon lagen uns in 6 Fällen Knochengewebe zur immunhistochemischen und autoradiographischen Evaluation vor. Die Immunhistochemie wurde mit einem anti-CXCR4 Antikörper durchgeführt. Des Weiteren wurden ein anti-CD3 und der anti-CXCR4-Antikörper zur Detektion CXCR4-exprimierender Lymphozyten am Ort der Entzündung mittels Doppel- Immunfluoreszenz verwendet. ERGEBNISSE: Die 68Ga-Pentixafor-PET/CT war bei 16 Patienten richtig positiv und bei 13 Patienten richtig negativ. Die Färbungen der verfügbaren Knochenpräparate waren sowohl in der Immunhistochemie als auch in der Autoradiographie deutlich positiv. In der Immunfluoreszenz konnten zudem CXCR4-exprimierende Lymphozyten am Ort der Entzündung in allen Proben nachgewiesen werden. Die Kontrolle eines Präparats einer nicht infizierten distalen Tibia zeigte dagegen keine CXCR4-oder CD3-Expression. FAZIT: Mit der 68Ga-Pentixafor-PET/CT können spezifisch CXCR4-exprimierende Lymphozyten am Ort der Entzündung nachgewiesen werden. Die 68Ga-Pentixafor-PET/CT stellt eine geeignete Methode in der Diagnostik chronischer Osteomyeltiden dar.

Dual time point 2-[18F]fluoro-2'-deoxyglucose positron emission tomography in chronic bacterial osteomyelitis.

OBJECTIVE: Quantitative dual time point imaging with [F]fluorodeoxyglucose positron emission tomography (F-FDG PET) has recently been found to be more accurate than single time point scanning in the discrimination between benign lesions and malignancy in various conditions. In our study we investigated glucose metabolism in chronic bacterial osteomyelitis (COM) by using F-FDG PET and a dual time protocol. METHODS: Seventeen non-diabetic patients with histopathologically proven COM and four non-diabetic patients with malignant bone disease were prospectively investigated with dual time F-FDG PET. All lesions were detected by their increased F-FDG uptake 30 and 90 min after injection of 370 MBq of F-FDG. The maximum and mean lesional standardized uptake values (SUV(max) and SUV(mean) after 30 and 90 min were determined. RESULTS: The median SUV(max) and SUV(mean) values of all osteomyelitic lesions at 30 min were 1.85 (range, 0.45-3.45) and 1.1 (range, 0.21-1.99), respectively. The median SUV(max) and SUV(mean) values of all malignant lesions at 30 min were 3.19 (range, 2.31-4.7) and 2.82 (range, 2.4-3.71), respectively. At 90 min the median SUV(max) and SUV(mean) of all osteomyelitic lesions were 1.78 (range, 0.4-2.93) and 1.1 (range, 0.18-1.72), respectively. At the same time point the median SUV(max) and SUV(mean) of all malignant lesions were 4.1 (range, 3.52-5.32) and 3.34 (range, 2.81-4.12), respectively. In osteomyelitis the SUV(max) and SUV(mean) between 30 and 90 min post-injection remained stable or decreased in 16/17 patients. In these patients a median decrease of 6% for SUV(max) (range, 1-31%) and a median decrease of 8.5% for SUV(mean) (range, 0-24%) was observed. Changes of SUV(max) and SUV(mean) between 30 and 90 min were highly significant (P<0.05). In one patient SUV(max) and SUV(mean) increased over the time. The histology of this patient revealed multiple foreign body granulomas in addition to a mononuclear infiltrate. In malignant lesions the SUV(max) and SUV(mean) between 30 and 90 min post-injection increased. CONCLUSION: Our preliminary results indicate that dynamic dual time point F-FDG PET provides a characteristic pattern in chronic osteomyelitis similar to inflammatory processes in other locations. This pattern may be of value in the differentiation between COM and malignant bone lesions.

Nuclear medicine studies in the dialysis patient.

Nuclear medicine (scintigraphy) studies that are performed in patients being prepared for regular dialysis treatment include the measurement of renal clearance and dynamic studies of renal perfusion and function. Static scintigraphy with 99mTc-DMSA may be used in the evaluation of children at risk of renal damage and further functional deterioration. In patients on peritoneal dialysis, nuclear medicine procedures enable the diagnosis of structural complications such as intra-abdominal herniations and leaks. Diagnosis of infections of the vascular access sites in patients on hemodialysis and of the catheter tunnel in patients on peritoneal dialysis can be made with high diagnostic accuracy using radiolabeled, autologous leukocytes. Scintigraphy is valuable in delineating the extent of deposits of amyloid and parenchymal microcalcifications, and may be helpful in the functional evaluation of organs and tissues involved in the pathophysiology of renal impairment and dialysis. If radioiodine therapy with 131I is performed in patients on hemodialysis with benign or malignant thyroid disease, then pretherapeutic dosimetry is necessary to avoid over- and undertreatment. Radioiodine therapy in the dialysis patient leads to only insignificant contamination of dialysis equipment and marginal exposure to the medical staff.