Molecular and cellular effects of radiotherapy on tumor microenvironment (TME) can help prime and propagate antitumor immunity. We hypothesized that delivering radiation to all tumor sites could augment response to immunotherapies. We tested an approach to enhance response to immune checkpoint inhibitors (ICIs) by using targeted radionuclide therapy (TRT) to deliver radiation semiselectively to tumors. NM600, an alkylphosphocholine analog that preferentially accumulates in most tumor types, chelates a radioisotope and semiselectively delivers it to the TME for therapeutic or diagnostic applications. Using serial ⁸⁶Y-NM600 positron emission tomography (PET) imaging, we estimated the dosimetry of ⁹⁰Y-NM600 in immunologically cold syngeneic murine models that do not respond to ICIs alone. We observed strong therapeutic efficacy and reported optimal dose (2.5 to 5 gray) and sequence for ⁹⁰Y-NM600 in combination with ICIs. After combined treatment, 45 to 66% of mice exhibited complete response and tumor-specific T cell memory, compared to 0% with ⁹⁰Y-NM600 or ICI alone. This required expression of STING in tumor cells. Combined TRT and ICI activated production of proinflammatory cytokines in the TME, promoted tumor infiltration by and clonal expansion of CD8⁺ T cells, and reduced metastases. In mice bearing multiple tumors, combining TRT with moderate-dose (12 gray) external beam radiotherapy (EBRT) targeting a single tumor augmented response to ICIs compared to combination of ICIs with either TRT or EBRT alone. The safety of TRT was confirmed in a companion canine study. Low-dose TRT represents a translatable approach to promote response to ICIs for many tumor types, regardless of location.

The aggregate-induced limitation for high power-conversion efficiencies (PCEs) of perylene-diimide (PDI):polymer solar cells can be circumvented when two simple rules are respected; the aggregate size of PDI remains short enough and the omnipresent PDI aggregates are electronically interconnected. Following these guidelines, a PCE of 3.7% is delivered by using the solution-processable, planar PDI monomer of N,N′-bis(1-ethylpropyl)-perylene-3,4,9,10-tetracarboxylic diimide as the electron acceptor mixed with the low-energy gap polymeric donor poly[(4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)-benzo[1,2-b;4,5-b′]dithiophene)-2,6-diyl-alt-(4-(2-ethylhexanoyl)-thieno[3,4-b]thiophene))-2,6-diyl] (PBDTTT-CT). The PBDTTT-CT:PDI composite absorbs strongly the light in the region of 400 nm–800 nm and after adding a small amount of 1,8-diiodooctane (DIO) efficient photocurrent generation is achieved. Space-charge limited dark current and transient photovoltage measurements suggest that the use of the DIO component optimizes the electron/hole carrier mobility ratio, suppresses the non-geminate recombination losses and improves the charge extraction efficiency.

Finding improved therapeutic strategies against T-cell Non-Hodgkin’s Lymphoma (NHL) remains an unmet clinical need. We implemented a theranostic approach employing a tumor-targeting alkylphosphocholine (NM600) radiolabeled with ⁸⁶Y for positron emission tomography (PET) imaging and ⁹⁰Y for targeted radionuclide therapy (TRT) of T-cell NHL. PET imaging and biodistribution performed in mouse models of T-cell NHL showed in vivo selective tumor uptake and retention of ⁸⁶Y-NM600. An initial toxicity assessment examining complete blood counts, blood chemistry, and histopathology of major organs established ⁹⁰Y-NM600 safety. Mice bearing T-cell NHL tumors treated with ⁹⁰Y-NM600 experienced tumor growth inhibition, extended survival, and a high degree of cure with immune memory toward tumor reestablishment. ⁹⁰Y-NM600 treatment was also effective against disseminated tumors, improving survival and cure rates. Finally, we observed a key role for the adaptive immune system in potentiating a durable anti-tumor response to TRT, especially in the presence of microscopic disease.

The present study describes a novel method for the low energy cyclotron production and radiochemical isolation of no-carrier-added ^132/135La³⁺ from bulk ^natBa. This separation strategy combines precipitation and single-column extraction chromatography to afford an overall radiochemical yield (92 ± 2%) and apparent molar activity (22 ± 4 Mbq/nmol) suitable for the radiolabeling of DOTA-conjugated vectors. The produced ^132/135La³⁺ has a radiochemical and radionuclidic purity amenable for ¹³²La/¹³⁵La-based cancer theranostic applications. Longitudinal PET/CT images acquired using the positron-emitting ¹³²La and ex vivo biodistribution data separately corroborated the accumulation of unchelated ^132/135La³⁺ ions in bone and the liver.