Retooling a Blood-Based Biomarker: Phase I Assessment of the High-Affinity CA19-9 Antibody HuMab-5B1 for Immuno-PET Imaging of Pancreatic Cancer.

PURPOSE: In patients with cancer who have an abnormal biomarker finding, the source of the biomarker in the bloodstream must be located for confirmation of diagnosis, staging, and therapy planning. We evaluated if immuno-PET with the radiolabeled high-affinity antibody HuMab-5B1 (MVT-2163), binding to the cancer antigen CA19-9, can identify the source of elevated biomarkers in patients with pancreatic cancer. PATIENTS AND METHODS: In this phase I dose-escalating study, 12 patients with CA19-9-positive metastatic malignancies were injected with MVT-2163. Within 7 days, all patients underwent a total of four whole-body PET/CT scans. A diagnostic CT scan was performed prior to injection of MVT-2163 to correlate findings on MVT-2163 PET/CT. RESULTS: Immuno-PET with MVT-2163 was safe and visualized known primary tumors and metastases with high contrast. In addition, radiotracer uptake was not only observed in metastases known from conventional CT, but also seen in subcentimeter lymph nodes located in typical metastatic sites of pancreatic cancer, which were not abnormal on routine clinical imaging studies. A significant fraction of the patients demonstrated very high and, over time, increased uptake of MVT-2163 in tumor tissue, suggesting that HuMab-5B1 labeled with beta-emitting radioisotopes may have the potential to deliver therapeutic doses of radiation to cancer cells. CONCLUSIONS: Our study shows that the tumor antigen CA19-9 secreted to the circulation can be used for sensitive detection of primary tumors and metastatic disease by immuno-PET. This significantly broadens the number of molecular targets that can be used for PET imaging and offers new opportunities for noninvasive characterization of tumors in patients.

Assessment of the lymphatic system in patients with diffuse lymphangiomatosis by magnetic resonance imaging.

OBJECTIVE: To assess the lymphatic system in patients with diffuse lymphangiomatosis by magnetic resonance imaging. MATERIALS AND METHODS: 15 patients with diffuse lymphangiomatosis were examined by magnetic resonance imaging. Three locations were examined: first, the lower leg and foot region; second, the upper leg and the knee region; and third, the pelvic with retroperitoneal and abdominal region. For magnetic resonance lymphangiography a T1-weighted 3D spoiled gradient-echo and a T2-weighted 3D-TSE sequence was used. RESULTS: The size of the genital lymphangiomas, which were revealed in all patients, varied between 5 and 83 mm. In 47% of the patients lymphangiomas were detected at the level of the lower legs, and in 87% of the patients at the level of the upper leg and retroperitoneum. Furthermore, lymphangiomas were seen in the inguinal and pelvic region in 100% and intraabdominally in 40% of the patients. The lymphangiomas extended into the abdominal wall in 93% of the examined patients. A chylous pleural effusion was revealed in 20% and a chylous ascites in 13% of patients. 93% of patients suffered due to the diffuse lymphangiomatous pathologies from a lymphedema of the lower extremities, while a generalized lymphedema of the trunk was found in 87% of the patients. CONCLUSION: Magnetic resonance imaging is a safe and accurate minimal-invasive imaging modality for the evaluation of the lymphatic system in patients with diffuse lymphangiomatosis. Since the localization and extension of the lymphangiomas are important prognostic factors, it is crucial to perform a safe radiologic evaluation with a high resolution for the patient's therapeutic planning.

MR lymphangiography for the assessment of the lymphatic system in patients undergoing microsurgical reconstructions of lymphatic vessels.

OBJECTIVE: To assess the morphology of the lymphatic system pre- and postoperatively in patients undergoing microsurgical reconstructions of the lymphatic vessels. MATERIALS AND METHODS: 8 lower extremities in 4 consecutive patients with secondary unilateral lymphedema of the lower extremities were examined by MR lymphangiography. 18 mL of gadoteridol and 1 mL of mepivacainhydrochloride 1% were subdivided into 10 portions and injected intracutaneously into the dorsal aspect of each foot at the region of the four interdigital webs and medial to the first proximal phalanx. MR imaging was performed with a 1.5-T system equipped with high-performance gradients. For MR lymphangiography a 3D-spoiled gradient-echo sequence was used. For evaluation of the lymphedema a heavily T2-weighted 3D-TSE sequence was performed. RESULTS: In 2 patients the 3D-TSE sequence demonstrated a decrease of the epifascial lymphedema in the postoperative acquisitions, whereby MR lymphangiography displayed an improvement of dermal-back areas and collateral lymphatic vessels. In one patient the epifascial lymphedema of the lower extremity decreased, whereas the diameter of the lymphatic vessels showed a constant diameter of 2 mm. In one patient with a lymphocutaneous fistula at the level of the right groin, the feeding lymphatic vessels and contrast media extravasation could clearly be visualized. The 3D-TSE sequence demonstrated an epi- as well as subfascial lymphedema of the right leg. CONCLUSION: MR lymphangiography is a safe and accurate diagnostic imaging method for the pre- and postoperative evaluation of the lymphatic circulation in patients undergoing microlymphatic surgery. Due to the minimal-invasiveness and lack of radiation, diagnostic follow-up MR lymphangiography examinations can be performed routinely and with no risk for the patient.

MRI and (18)FDG-PET in the assessment of bone marrow infiltration of the spine in cancer patients.

The aim of this study was to evaluate the diagnostic value of MRI and (18)FDG-PET in bone marrow infiltration of the spine due to metastases of solid tumours and lymphoma in cancer patients. In 35 cancer patients (solid tumours n = 26, lymphoma n = 9) MRI of the spine and (18)FDG-PET were reviewed and the detectability of metastases, infiltration of the spine, extent of disease, and therapeutic implications were compared. In 8/35 cases (23%) imaging technique showed concordantly no bone marrow infiltration. In 19/35 patients (54%), both MRI and (18)FDG-PET revealed bone marrow infiltration of the axial skeleton. In 12/19 patients (63%), MRI showed more extensive disease which lead to subsequent therapy. The imaging findings of MRI and (18)FDG-PET were discordant in 8/35 cases (23%). (18)FDG-PET was false positive in two patients. In six patients, (18)FDG-PET failed to detect bone metastases and bone marrow infiltration of the spine, which was detected by MRI and proven by clinical follow-up with subsequent therapy in two cases. MRI is more sensitive and specific than (18)FDG-PET detecting bone marrow metastases and infiltration of the spine and has a great impact in staging cancer patients.

Assessment of anal fistulas with high-resolution subtraction MR-fistulography: comparison with surgical findings.

PURPOSE: To investigate a new MR-imaging protocol defined as subtraction MR-fistulography for the detection of fistula-in-ano. MATERIALS AND METHODS: A total of 36 patients (18 men, 18 women) with the clinical diagnosis of anal fistula or abscess who were scheduled for surgical exploration were preoperatively imaged at 1.5 T in the supine position; coronal STIR sequences and axial T1-weighted three-dimensional FLASH sequences before and after intravenous injection of gadobenate dimeglumine (Gd-BOPTA) were obtained. Image subtraction was routinely used. The image findings were compared with the findings at surgical exploration according to a uniform classification system. RESULTS: A total of 46 fistulas were seen on subtraction MR-fistulography, whereas surgery described 41 fistulas. MRI and surgery concordantly depicted a total number of 40 fistulas, six fistulas were only described by MRI, and one fistula was only seen during surgery. A total of 27 abscesses were detected with MRI, compared to 22 during surgery. A total of 22 abscesses were concordantly diagnosed. Complete agreement between subtraction MR-fistulography and surgery occurred in 32 (89%) of the 36 patients. The four patients in whom both procedures disagreed had complex anal sepsis with multiple fistulas and/or abscesses due to Crohn disease. CONCLUSION: High-resolution subtraction MR-fistulography is an important complement to surgical exploration and especially suitable for investigating complex anal sepsis.