A further advantage is that the white fur of this albino strain makes in vivo imaging more sensitive and simpler to perform than in mice with black fur. This finding was not anticipated since MOPCs are generally considered to be poor models of MM bone disease, even though they readily form extramedullary plasmacytomas after local injection. It may be that Mechlorethamine hydrochloride MOPC315 has an increased tropism for bone marrow compared to other MOPC lines and bone marrow tropism may thereby vary Folinic acid calcium salt pentahydrate between different MOPC lines. The results further demonstrate that variants of the MOPC315 cell line can be obtained that more rapidly induces MMlike bone disease. Thus, a cell line selected for high tumor take by s.c. injection, MOPC315.4, caused paraplegia in all i.v.-injected mice within 65 days. After 9 cycles of i.v. injection of MOPC315.4 and recovery of cells from femurs of paraplegic mice, the MOPC315.BM cell line was obtained that following i.v. injection caused paraplegia in all mice within 35 days. It is unclear whether the consecutive s.c. and i.v. selection procedures resulted in either a gradual change of phenotype or in a selection of rare cells with more MM-like features, pre-existing in the parental plasmacytoma cell line. The fact that decreasing amounts of injected cells were needed with progressive cycles could indicate that the in vivo-selection might have enriched for a pre-existing variant. It is also unknown whether preferential growth in bone marrow was due to increased homing to the bone, or if cells simply grew better once they had settled in the bone marrow microenvironment or both. MOPC315.BM cells labeled with firefly luciferase could be followed by repeated bioluminescent imaging of i.v.-injected mice. Overall, the results were similar in normal BALB/c and T cell-deficient BALB/c nu/nu mice. However, sensitivity was clearly higher in furless BALB/c nu/nu mice, the nude strain being the recommended model for DLIT. Sensitivity was further increased by injection of a higher number of cells. Immediately after injection, cells were found primarily in the lung, but also in the spleen and the liver. However, and importantly, a minor fraction of cells were found in the tibiofemoral region already 1 h after injection. Early invasion of bone marrow is consistent with results obtained with i.v. injection of 51Cr-labeled 5T2MM cells. The spleen signal progressed with time, while lung and liver signals decreased. Affection of other organs was only infrequently detected. MM growth in spleen is consistent with extramedullary hematopoiesis in this organ, and is also found in the 5TMM models. It is generally believed that MM cells represent malignant counterparts of plasma cells that at the earlier B cell stage have been through a germinal center reaction. However, it is unclear where the neoplastic process initially takes place. One possibility is that MM originates from plasma cells malignantly transformed within the bone marrow, and that MM cells later metastasize to other bones. Another possibility is that neoplastic cells originate in an extramedullary site, and then seed multiple bones where they are exposed to a microenvironment conducive to growth. Several pieces of evidence support the latter possibility. Firstly, MM has been associated with less differentiated clonogenic precursors found in blood. Secondly, extramedullary plasmacytomas in humans can metastasize to bone. Thirdly, ileocecal plasmacytoma in an aged gonadectomized mouse, as well as transplanted MOPC tumors, can metastasize to the bone marrow.