ASL perfusion imaging is useful for differentiating PCNSLs from GBMs as well as DWI and FDG-PET.

Near-infrared photoimmunotherapy (NIR-PIT) induces immunogenic cell death but has mostly failed to induce durable antitumor responses in syngenic tumor mouse models. We hypothesized that adaptive immune resistance could be limiting durable responses after treatmemt with NIR-PIT. We investigated the effects of combining NIR-PIT targeting cell-surface CD44 and PD-1 blockade in multiple syngeneic tumor models. In two of three models, NIR-PIT monotherapy halted tumor growth, enhanced dendritic cell tumor infiltration, and induced de novo tumor antigenspecific T-cell responses absent at baseline. The addition of PD-1 blockade reversed adaptive immune resistance, resulting in both enhanced preexisting tumor antigenspecific T-cell responses and enhanced de novo T-cell responses induced by NIR-PIT. Enhanced immune responses correlated with shared tumor antigen expression, suggesting that antigenicity is a major determinant of response to combination NIR-PIT and PD-1 blockade. Combination treatment induced complete rejection of MC38 tumors treated with NIR-PIT, as well as untreated, distant tumors. Accordingly, tumor antigen-specific T-cell responses were measured in both treated and untreated tumors, validating the development of systemic antitumor immunity. Mice that cleared tumors resisted subsequent tumor challenge, indicating the presence of systemic immune memory. Cumulatively, these results demonstrate reversal of adaptive immune resistance following induction of innate and adaptive immunity by NIR-PIT, resulting in high rates of tumor rejection and/or significant tumor growth control in antigenic syngeneic models of cancer.

In oncology, the apparent diffusion coefficient (ADC) measured by diffusion-weighted MR imaging (DWI) and the standardized uptake value (SUV) from 18 F-FDG PET have similar clinical applications. The purpose of this study was to assess the correlation between the ADC and SUV and compare their potential in the diagnosis and prediction of prognosis in breast tumors. Methods: Seventy-nine female patients (age range, 19-69 y; average, 49.1 y) with 83 pathologically proven breast tumors were recruited. The diagnoses consisted of 70 malignant breast tumors (65 cases of invasive ductal carcinoma, 1 of medullary carcinoma, 1 of mucinous carcinoma, 1 of squamous cell carcinoma, and 2 of micropapillary carcinoma) and 13 benign breast tumors (4 cases of fibroadenoma, 4 of mastopathy, 3 of adenosis with atypia, and 2 of benign phyllodes tumor). All patients underwent mammary gland MR imaging with DWI and 18 F-FDG PET within a 2-wk interval. The patients' ADCs and SUVs were measured within the tumor by DWI and 18 F-FDG PET, respectively. For the malignant tumors, we evaluated the relationships among ADC, SUV, histopathologic appearance, and long-term prognosis. Results: A significant difference (P , 0.05) was observed in both parameters (ADC and SUV) between the benign and malignant breast tumors, and the difference was more significant when we introduced a new parameter, SUV/ADC. There was a weak inverse correlation between ADC and SUV (r 5 −0.36; P 5 0.06) among the total tumors; however, this correlation was not significant within the group of malignant tumors. High SUV was found to correlate with larger tumor size, higher nuclear grade, and the triple-negative hormonal receptor profile. High ADC was revealed to be correlated with negative progesterone receptor and positive human epidermal growth factor receptor 2 profile. Higher SUVs also showed a correlation with poor prognosis. No correlation was seen between ADC and prognosis. Conclusion: Both SUV and ADC are helpful parameters in differentiating benign from malignant breast tumors. The use of SUV and ADC in combination may help in the diagnosis because of their inverse relationship. High preoperative SUV was associated with poor prognosis, but the contribution of ADC to prognosis prediction was small.

Oral cavity squamous cell carcinoma (OSCC) is considered one of the most aggressive subtypes of cancer. Anti-CD44 monoclonal antibodies (mAbs) are a potential therapy against CD44 expressing OSCC, however, to date the therapeutic effects have been disappointing. Here, a new cancer treatment is described, near-infrared photoimmunotherapy (NIR-PIT), that uses anti-CD44 mAbs conjugated to the photoabsorber, IR700DX. This conjugate is injected into mice harboring one of three CD44 expressing syngeneic murine oral cancer cell (MOC) lines, MOC1 (immunogenic), MOC2 mKate2 (moderately immunogenic), and MOC2-luc (poorly immunogenic). Binding of the anti-CD44-IR700 conjugate was shown to be specific and cell-specific cytotoxicity was observed after exposure of the cells to NIR in vitro. The anti-CD44-IR700 conjugate, when assessed in vivo, demonstrated deposition within the tumor with a high tumor-to-background ratio. Tumor-bearing mice were separated into four cohorts: no treatment; 100μg of anti-CD44-IR700 i.v. only; NIR light exposure only; and 100μg of anti-CD44-IR700 i.v. with NIR light exposure. NIR-PIT therapy, compared with the other groups, significantly inhibited tumor growth and prolonged survival in all three cell model systems. In conclusion, these data reveal that anti-CD44 antibodies are suitable as mAb-photoabsorber conjugates for NIR-PIT in MOC cells.

Prostate-specific membrane antigen (PSMA) is a membrane protein that is overexpressed manifold in prostate cancer and provides an attractive target for molecular therapy. Near infrared photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that employs an antibody-photo-absorber conjugate (APC). Here, we describe the efficacy of NIR-PIT, using a fully human IgG1 anti-PSMA monoclonal antibody (mAb), conjugated to the photo-absorber, IR700DX, in a PSMA expressing PC3 prostate cancer cell line. Anti-PSMA-IR700 showed specific binding and cell-specific killing was observed after exposure of the cells to NIR in vitro. In the in vivo study, anti-PSMA-IR700 showed high tumor accumulation and high tumor-background ratio. Tumor-bearing mice were separated into 4 groups: (1) no treatment; (2) 100 μg of anti-PSMA-IR700 i.v.; (3) NIR light exposure; (4) 100 μg of anti-PSMA-IR700 i.v., NIR light exposure was administered. These were performed every week for up to 3 weeks. Tumor growth was significantly inhibited by NIR-PIT treatment compared with the other control groups (p < 0.001), and significantly prolonged survival was achieved (p < 0.0001 vs other control groups). More than two thirds of tumors were cured with NIR-PIT. In conclusion, the anti-PSMA antibody is suitable as an APC for NIR-PIT. Furthermore, NIR-PIT with the anti-PSMA-IR700 antibody is a promising candidate of the treatment of PSMA-expressing tumors and could be readily translated to humans.

Objective This trial was conducted to evaluate the ability of pazopanib to overcome therapeutic 131 I resistance. Materials, methods and patients This phase 1 trial assesses the combination of pazopanib and escalating doses of radioiodine (131 I) in patients with recurrent or metastatic thyroid cancer that are borderline or relatively iodine refractory. Radioiodine uptake scans were assessed post therapy and compared to historical pre-treatment scans. Patients underwent FDG PET/CT before and after the initial pazopanib treatment to identify the impact of pazopanib on the cancer prior to 131 I therapy.

Near infrared photoimmunotherapy (NIR-PIT) is a newly-developed cancer therapy in which a monoclonal antibody is conjugated to a near-infrared photoabsorber, IR700 to form an antibody photoabsorber conjugate (APC). After the APC binds to cancer cells expressing the cognate antigen, exposure to NIR light results in rapid, highly selective necrotic cell death of the cancer cells with minimal off-target effects. Several hours after NIR-PIT, the tumor vessels become supraphysiologically permeable and circulating APC can therefore readily leak into the already-treated tumor space where it can bind with viable cancer cells that is called super-enhanced permeability and retention effect. The presence of the SUPR effect after NIR-PIT has prompted regimens in which there is a repeat exposure of NIR light 24 hours after the initial NIR-PIT to take advantage of the leakage of additional APC deeper into the tumor. However, this post-treatment APC penetration was fully induced within 3 hours, therefore, it is possible that repeated exposures of NIR light could be administered much earlier than 24 hours and still produce the same effects. To test this idea, we compared several modes of delivering additional doses of light after initial NIR-PIT. We found that repeated exposures of NIR light starting 3 hours after initial NIR-PIT produced equal or superior results to more delayed exposures of NIR light. This finding has practical implications of an easy-to-perform regimen as repeated light exposures could be performed during a single day rather than extending the procedure over two days which is the current recommendation.

Near-infrared photoimmunotherapy (NIR-PIT), a promising cancer therapy utilizing an antibody-photoabsorber conjugate (APC) and NIR light, which induces rapid necrotic cell death only in APC-bound cells. Effective NIR-PIT in mouse models has been achieved using superficial light illumination (SLI) with light emitting diodes (LEDs) or lasers, but in the clinical setting, fiber optic diffusers have been employed to deliver light to deeper tumors. However, the performance of NIR light in tissue delivered by fiber optic diffusers is poorly understood. Here, we investigated NIR-PIT using a cylindrical fiber optic diffuser in a mouse model of A431 tumors. NIR-PIT with 100 J/cm, the same light dose used in clinical trials of NIR-PIT, was applied after insertion of the diffuser within the tumor bed, and then both bioluminescence and fluorescence imaging were analyzed to assess the therapeutic efficacy. The diffuser can deliver adequate NIR light dose for effective NIR-PIT to the A431 tumor at a distance of approximately 1 cm around the light source at 100 J/cm. At 50 J/cm NIR light effective NIR-PIT was reduced to a distance of 5 -7 mm diameter around the light source. These results indicate that the energy of interstitial light (measured in Joules/cm) administered via a fiber diffuser determines the depth of effective NIR-PIT around the diffuser and determines the spacing at which such diffusers should be placed to entirely cover the tumor. Thermal measurements demonstrate that interstitial light for NIR-PIT does not cause damage to the skin overlying the diffuser.