An Effective Immuno-PET Imaging Method to Monitor CD8-Dependent Responses to Immunotherapy.

The rapidly advancing field of cancer immunotherapy is currently limited by the scarcity of noninvasive and quantitative technologies capable of monitoring the presence and abundance of CD8(+) T cells and other immune cell subsets. In this study, we describe the generation of (89)Zr-desferrioxamine-labeled anti-CD8 cys-diabody ((89)Zr-malDFO-169 cDb) for noninvasive immuno-PET tracking of endogenous CD8(+) T cells. We demonstrate that anti-CD8 immuno-PET is a sensitive tool for detecting changes in systemic and tumor-infiltrating CD8 expression in preclinical syngeneic tumor immunotherapy models including antigen-specific adoptive T-cell transfer, agonistic antibody therapy (anti-CD137/4-1BB), and checkpoint blockade antibody therapy (anti-PD-L1). The ability of anti-CD8 immuno-PET to provide whole body information regarding therapy-induced alterations of this dynamic T-cell population provides new opportunities to evaluate antitumor immune responses of immunotherapies currently being evaluated in the clinic.

99mTc-interleukin-2 scintigraphy as a potential tool for evaluating tumor-infiltrating lymphocytes in melanoma lesions: a validation study.

UNLABELLED: Cutaneous melanoma is often characterized by the presence of tumor-infiltrating lymphocytes (TILs). The degree of such infiltration and cell activation are considered significant prognostic factors reflecting the host's immune response to the tumor; thus, patients with peritumoral infiltration may have a better prognosis and may also achieve a better response to interleukin-2 (IL2) immunotherapy. There is evidence that the expression of cluster designation (CD) 25 antigen (IL2 receptor [IL2R]) is a good marker of activity of T lymphocytes against melanoma cells. The aim of this study was to evaluate in vivo the binding of 99mTc-IL2 to lymphocytes infiltrating cutaneous melanoma and to determine whether such uptake correlates with immunologic and histologic data, thus providing useful prognostic information for IL2 therapy in patients with advanced disease. METHODS: Thirty patients with cutaneous lesions suspected of being melanoma were studied. Planar gamma-camera images over known tumor sites were acquired 1 h after the injection of 111-185 MBq of 99mTc-IL2. Tumor uptake of 99mTc-IL2 was measured as a target-to-background (T/B) radioactivity ratio. All patients underwent surgery, and histologic evaluation of the resected lesion was performed. The percentage of different peripheral blood lymphocyte subsets (CD3, CD4, CD8, CD16, CD25) and the percentage of IL2R-positive tumor cells on histologic sections were also measured. RESULTS: At final histology, 21 lesions were found to be melanoma and 9 were classified as benign. In 15 of 21 (71%) melanomas and 2 of 9 (22%) benign cutaneous lesions, we found uptake of 99mTc-IL2. The calculated T/B ratios correlated significantly with the number of IL2R-positive TILs. CONCLUSION: 99mTc-IL2 scintigraphy provides a means of in vivo measurement of the extent of tumor infiltration of IL2R-positive cells, thereby providing valuable prognostic information for selection of patients who may benefit from IL2 immunotherapy.

A preliminary study on the functional analysis of peripheral blood lymphocytes from ovarian cancer patients developing HAMA after immunoscintigraphy.

In the follow-up of ovarian cancer patients, rising levels of the tumor-associated antigen CA 125 are an indication for immunoscintigraphy. Human anti-mouse antibodies (HAMA) are frequently found after immunoscintigraphy with murine MAb directed against CA 125. Since we observed that patients developing high HAMA-levels in serum remained free of tumor or had stable disease, we examined the cytotoxic activity of peripheral blood lymphocytes (PBL) by a fluorescence-based assay. Our results demonstrate that PBLs of patients with high anti-idiotypic antibodies show an increased cytotoxic activity (by a factor of 4) compared to those of patients with low HAMA levels. The clinical course of the patients after the first injection of murine monoclonal antibody was observed over a period of 1 to 3 years. Improvement or deterioration of patients' clinical condition corresponded with the results obtained by functional analysis. Further investigations concerning the course of cytotoxic activity in HAMA-positive patients will have to clarify HAMA's role in the immune response.

[Lymphocytic infiltrations of the orbit in MRT and CT. Lymphoma, pseudolymphoma and inflammatory pseudotumor]. / Lymphozytäre Infiltrationen der Orbita in MRT und CT. Lymphom, Pseudolymphom und entzündlicher Pseudotumor.

MR and CT examinations of 16 patients with lymphoma, pseudolymphoma and inflammatory pseudotumours were analysed to describe morphologic features of lymphocytic infiltration. Density and signal did not allow for differentiation, but localisation was the most important criterion: lymphoma and pseudolymphoma were located in the anterior superior orbit, inflammatory pseudotumours being retrobulbar lesions. Differentiation is of clinical importance, since both lymphoma and pseudolymphoma are accompanied by generalised malignant lymphoma while inflammatory pseudotumours are localised. Imaging of topographic relations of lens, optic nerve and lesion on sagittal MR images was found helpful for radiation therapy planning.

Imaging of metastatic colorectal cancer with tumour-activated killer lymphocytes.

Adoptive immunotherapy may be useful for treating or visualising metastatic cancer. Lymphocytes were taken from 6 patients with metastatic colorectal cancer and cultured with cells from the patients primary tumour to produce tumour-activated killer (TAK) lymphocytes. We re-injected each patient with IIIIn-labelled TAK cells in order to visualise metastases. Images were taken with a gamma-camera for up to 48 h after injection. Metastases were revealed as early as 4 h in the lung and as late as 48 h in the abdomen. Liver images produced "cold" spots corresponding to metastatic lesions. Lymph nodes were not visualised. Re-injection of TAK cells raised against autologous colorectal tumours reveals the sites of metastases.