Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of antibodies for targeting tumors with the toxicity induced by photon absorbers after irradiation with NIR light¹. NIR-PIT induces nearly immediate necrotic cell death, rather than apoptotic cell death which is more typical of the majority of cancer treatments. Within minutes, cells treated with NIR-PIT rapidly increase in volume leading to rupture of the cell membrane, and extrusion of cell contents into the extracellular space ¹. Moreover, because the antibody- photon absorber conjugate (APC) tends to preferentially bind to the layers of cells in the immediate perivascular space, NIR-PIT leads to perivascular tumor cell death thereby promoting marked increases in vascular permeability particularly for nano-sized agents ². The dramatic increase in permeability for nano-sized agents, followed by their retention in treated tumors has been termed ‘super-enhanced permeability and retention (SUPR)’ . These changes occur within 20 min of NIR light exposure even while gross tumor size and shape are not changed. The purpose of this study was to determine if MR imaging can detect changes in the MR properties of tumor within several hours of NIR-PIT.A431 cells were injected subcutaneously in the right and left dorsi of 12 mice. Six days later, the mice were injected with a photon absorber, IR-700, conjugated to panitumumab, an antibody targeting epidermal growth factor receptor (EGFR1). One day later, only right sided tumors were exposed to NIR light (treated tumor). MRI was performed 1 day before and 1-2 hours after NIR-PIT using albumin binding gadofosveset for six mice and low molecular weight gadopentetate dimeglumine for another six mice. T2 relaxation times and the apparent diffusion coefficient (ADC) (using the following combinations of b-values: 0-1000, 200-1000 and 500-1000 s/mm² ) and enhancement indices were compared before and after NIR-PIT using a two-sided paired t-test.Post treatment T2 relaxation times and the three ADC values are shown in Table 1. For treated tumors, T2 relaxation time increased after NIR-PIT (p < 0.01) and all three ADC values decreased after NIR-PIT (p < 0.01). For non-treated tumors, for the b= 0 and 1000 s/mm² pair, a decline in ADC was seen (p=0.04) but was not seen with the combinations of b=200 and 1000 (p=0.13) or b=500 and 1000 s/mm² (p=0.07) (Fig. 1). Moreover, the enhancement area under the curve (AUC) using gadofosveset increased after NIR-PIT (p = 0.02) (Fig. 2a, 3a). For non-treated tumors maximum relative enhancement (MRE) and AUC using gadofosveset decreased after NIR-PIT (p = 0.02, and 0.03, respectively) (Fig. 2b, 3b). No significant differences were observed in either treated or non-treated tumors using gadopentetate dimeglumine.This study demonstrates that NIR-PIT induces rapid changes in the MR properties of tissues that can be readily measured using standard MR pulse sequences available on practically all MRI units. For instance, T2 relaxation time was increased after NIR-PIT probably because of rapid cell volume expansion leading to increased water content in tissue and edema in the tumor bed due to increases in vascular permeability^1,2. Similarly, it is likely that cell expansion and the increased viscosity of the extracellular space due to cell rupture after NIR-PIT leads to lowering water diffusion. Moreover, vascular permeability, as measured by increased retention of the macromolecular gadofosveset (when bound to albumin) as compared to the lack of increased retention with the low molecular weight gadopentetate dimeglumine immediately after NIR-PIT, appears to increase after NIR-PIT. Thus, NIR-PIT causes profound and early changes in in treated tumors on multiple MRI features including T2, ADC and DCE MRI.Prolongation of T2, reductions in ADC and increased enhancement using gadofosveset are seen within 2 hours of NIR-PIT treatment of tumors. Thus, MRI can be a useful imaging biomarker for detecting early therapeutic changes after NIR-PIT.