What is the Best Radionuclide for Immuno-PET of Multiple Myeloma? A Comparison Study Between 89Zr- and 64Cu-Labeled Anti-CD138 in a Preclinical Syngeneic Model.

Although positron emission tomography (PET) imaging with 18-Fluorodeoxyglucose (18F-FDG) is a promising technique in multiple myeloma (MM), the development of other radiopharmaceuticals seems relevant. CD138 is currently used as a standard marker for the identification of myeloma cells and could be used in phenotype tumor imaging. In this study, we used an anti-CD138 murine antibody (9E7.4) radiolabeled with copper-64 (64Cu) or zirconium-89 (89Zr) and compared them in a syngeneic mouse model to select the optimal tracers for MM PET imaging. Then, 9E7.4 was conjugated to TE2A-benzyl isothiocyanate (TE2A) and desferrioxamine (DFO) chelators for 64Cu and 89Zr labeling, respectively. 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 antibodies were evaluated by PET imaging and biodistribution studies in C57BL/KaLwRij mice bearing either 5T33-MM subcutaneous tumors or bone lesions and were compared to 18F-FDG-PET imaging. In biodistribution and PET studies, 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 displayed comparable good tumor uptake of subcutaneous tumors. On the bone lesions, PET imaging with 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 showed higher uptake than with 18F-FDG-PET. Comparison of both 9E7.4 conjugates revealed higher nonspecific bone uptakes of 89Zr-DFO-9E7.4 than 64Cu-TE2A-9E7.4. Because of free 89Zr's tropism for bone when using 89Zr-anti-CD138, 64Cu-anti-CD138 antibody had the most optimal tumor-to-nontarget tissue ratios for translation into humans as a specific new imaging radiopharmaceutical agent in MM.

Occupational Exposure to Veterinary Workers from the Positron Emission Tomography Imaging Agent 64Cu-ATSM.

Cu-ATSM is an emerging radiopharmaceutical for diagnostic use in positron emission tomography (PET), but to date there are no studies that assess the potential occupational doses to workers in either human or veterinary medicine. This study was aimed at determining the external radiation dose to veterinary workers from clinical PET/CT (PET combined with computed tomography) procedures using Cu-ATSM. To determine the dose to the workers, each worker was assigned two Electronic Personal Dosimeters (EPDs) to be worn on the chest and waist during the entirety of each procedure. The workers monitored during this study included a radiobiologist, a nuclear medicine technologist, an anesthesiologist, and a veterinary surgeon. Seven canine patients were imaged with an average mass of 33.7 kg (a range of 20.0-55.1 kg) with an average injected activity of 5 MBq kg. The dose range for the radiobiologist was 2-17 µSv (mean of 7.1 µSv), for the nuclear medicine technologist 0-14 µSv (mean of 5.6 µSv), for the anesthesiologist 0-12 µSv (mean of 4.0 µSv), and for the surgeon 0-10 µSv (mean of 3.6 µSv). In a comparison between the results of this study and published literature on occupational exposures from veterinary FDG PET/CT procedures, Cu-ATSM veterinary PET/CT procedures, on a per patient bias, exposed workers to less radiation.

CuS Nanodots with Ultrahigh Efficient Renal Clearance for Positron Emission Tomography Imaging and Image-Guided Photothermal Therapy.

Translation of nanoparticles (NPs) into clinical practice has been limited by toxic effects induced by nonspecific accumulation of NPs in healthy organs after systemic administration. The ideal NPs should accumulate in the target site, carry out their function, and then ultimately be eliminated from the body. Here, we show a single-compartment, multifunctional ultrasmall copper sulfide nanodot (CuS ND) that is rapidly cleared from the body. These CuS NDs have a hydrodynamic diameter of <6 nm, can efficiently absorb near-infrared light for photothermal ablation therapy, and stably incorporate the copper-64 radioisotope for noninvasive positron emission tomography (PET). Importantly, ∼95% of CuS NDs are excreted intact through the renal-urinary system within 24 h with minimal retention in the liver and the spleen. The ultrasmall CuS NDs accumulate in 4T1 tumors in Balb/c mice, as monitored by PET imaging, and mediate tumor ablation when combined with near-infrared light irradiation. As a first example of PET-visible, renal-clearable inorganic nanomaterials with peak absorption in the near-infrared region, CuS NDs represent a robust platform for cancer imaging and therapy.

67Cu-2IT-BAT-Lym-1 pharmacokinetics, radiation dosimetry, toxicity and tumor regression in patients with lymphoma.

UNLABELLED: Lym-1, a monoclonal antibody that preferentially targets malignant lymphocytes, has induced therapeutic responses and prolonged survival in patients with non-Hodgkin's lymphoma when labeled with 1311. Radiometal-labeled antibodies provide higher tumor radiation doses than corresponding 1311 antibodies. 67Cu has an exceptional combination of properties desirable for radioimmunotherapy, including gamma and beta emissions for imaging and therapy, respectively, a biocompatible half-time and absence of pathways contributing to myelotoxicity. The radioimmunoconjugate, 67Cu-21T-BAT-Lym-1, has been shown to be efficacious in nude mice bearing human Burkitt's lymphoma (Raji) xenografts. Based on these results, a clinical study of the pharmacokinetics and dosimetry of 67Cu-21T-BAT-Lym-1 in patients with lymphoma was initiated. METHODS: Eleven patients with advanced stage 3 or 4 lymphoma were given a preload dose of unmodified Lym-1, then an imaging dose of 126-533 MBq (3.4-14.4 mCi) 67Cu-21T-BAT-Lym-1. Total Lym-1 ranged from 25 to 70 mg dependent on the specific activity of the radioimmunoconjugate and was infused at a rate of 0.5-1 mg/min. Imaging, physical examination, including caliper measurement of superficial tumors, and analysis of blood, urine and fecal samples were performed for a period of 6-13 d after infusion to assess pharmacokinetics, radiation dosimetry, toxicity and tumor regression. RESULTS: In 7 patients, in whom superficial tumors had been accurately measured, tumors regressed from 18% to 75% (mean 48%) within several days of 67Cu-21T-BAT-Lym-1 infusion. The uptake and biological half-time of 67Cu-21T-BAT-Lym-1 in tumors were greater than those of normal tissues, except the mean liver half-time exceeded the mean tumor half-time. The mean tumor-to-marrow radiation ratio was 32:1, tumor-to-total body was 24:1 and tumor-to-liver was 1.5:1. Images were of very good quality; tumors and normal organs were readily identified. Mild and transient Lym-1 toxicity occurred in 6 patients; 1 patient developed a human antimouse antibody. There were no significant changes in blood counts or serum chemistries indicative of radiation toxicity. CONCLUSION: Because of the long residence time of 67Cu-21T-BAT-Lym-1 in tumors, high therapeutic ratios were achieved and, remarkably, numerous tumor regressions were observed after imaging doses. The results indicate considerable therapeutic potential for 67Cu-21T-BAT-Lym-1.

Radioimmunotherapy of lymphoma: a UC Davis experience.

B-cell malignancies, such as malignant lymphoma and chronic lymphocytic leukemia, commonly present with advanced disease and multiple sites of involvement. Consequently, systemic combination chemotherapy is the standard therapeutic approach and cures about one half of these patients. Development of novel therapies is required if the remaining patients are to be cured of their malignancy. Lym-1, a mouse monoclonal antibody that is reactive with these malignancies, has been coupled with 131I or 67Cu and used to treat 55 patients with advanced B-cell malignancies that had proven resistant to standard therapy. The majority of the patients responded to this therapy and the survival of responders was longer than that of non-responders. Similar results have recently been reported by others. These results represent a remarkable achievement for single agent therapy because these trials were exploratory in nature and most of the patients had failed many chemotherapy regimens. The toxicities were in general mild and readily manageable. It appears that enhancing strategies are likely to improve upon these results by increasing the therapeutic index.