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Photothermal therapy (PTT) is a promising cancer therapeutic approach due to its spatial selectivity and high potency. Indocyanine green (ICG) has been considered a biocompatible PTT agent. However, ICG has several challenges to hinder its clinical use including rapid blood clearance and instability to heat, light, and solvent, leading to a loss of photoactivation property and PTT efficacy. Herein, we leveraged stabilizing components, methyl-β-cyclodextrin and liposomes, in one nanoplatform (ICD lipo) to enhance ICG stability and the photothermal therapeutic effect against cancer. Compared to ICG, ICD lipo displayed a 4.8-fold reduction in degradation in PBS solvent after 30 days and a 3.4-fold reduction in photobleaching after near-infrared laser irradiation. Moreover, in tumor-bearing mice, ICD lipo presented a 2.7-fold increase in tumor targetability and inhibited tumor growth 9.6 times more effectively than did ICG without any serious toxicity. We believe that ICD lipo could be a potential PTT agent for cancer therapeutics.

Nanoparticles are primarily taken up by immune cells after systemic administration. Thus, they are considered an ideal drug delivery vehicle for immunomodulation. Because the spleen is the largest lymphatic organ and regulates the systemic immune system, there have been studies to develop spleen targeting nanoparticles for immunomodulation of cancer and immunological disorders. Inflammatory bowel disease (IBD) includes disorders involving chronic inflammation in the gastrointestinal tract and is considered incurable despite a variety of treatment options. Hydrogen sulfide (H2S) is one of the gasotransmitters that carries out anti-inflammatory functions and has shown promising immunomodulatory effects in various inflammatory diseases including IBD. Herein, we developed a delicately tuned H2S donor delivering liposome for spleen targeting (ST-H2S lipo) and studied its therapeutic effects in a dextran sulfate sodium (DSS) induced colitis model. We identified the ideal PEG type and ratio of liposome for a high stability, loading efficiency, and spleen targeting effect. In the treatment of the DSS-induced colitis model, we found that ST-H2S lipo and conventional long-circulating liposomes loaded with H2S donors (LC-H2S lipo) reduced the severity of colitis, whereas unloaded H2S donors did not. Furthermore, the therapeutic effect of ST-H2S lipo was superior to that of LC-H2S lipo due to its better systemic immunomodulatory effect than that of LC-H2S lipo. Our findings demonstrate that spleen targeting H2S lipo may have therapeutic potential for IBD.

The development of molecular imaging probes to identify key cellular changes within lung metastases may lead to noninvasive detection of metastatic lesions in the lung. In this study, we constructed a macrophage-targeted clickable albumin nanoplatform (CAN) decorated with mannose as the targeting ligand using a click reaction to maintain the intrinsic properties of albumin in vivo. We also modified the number of mannose molecules on the CAN and found that mannosylated serum albumin (MSA) harboring six molecules of mannose displayed favorable pharmacokinetics that allowed high-contrast imaging of the lung, rendering it suitable for in vivovisualization of lung metastases. Due to the optimized control of functionalization and surface modification, MSA enhanced blood circulation time and active/passive targeting abilities and was specifically incorporated by mannose receptor (CD206)-expressing macrophages in the metastatic lung. Moreover, extensive in vivoimaging studies using single-photon emission computed tomography (SPECT)/CT and positron emission tomography (PET) revealed that blood circulation of time-optimized MSA can be used to discern metastatic lesions, with a strong correlation between its signal and metastatic burden in the lung.

Brain dopamine neurotransmission is regulated by the dopamine transporter (DAT), which drives reuptake of extracellular dopamine into the presynaptic neurons. We hypothesized that the glucose loading dose would affect the striatal DAT availability. An i.v. bolus injection of 18F-FP-CIT was administered after infusion of low-dose glucose (300 mg/kg), high-dose glucose (600 mg/kg) or placebo (normal saline). The emission data were acquired over 90 min in 23 healthy male subjects. Substantial increases of binding potential (BPNDs) from ventral striatum (VST), caudate nucleus, and putamen were observed after low-dose glucose loading (+26.0, +87.0, and +37.8%) and after high-dose glucose loading (+10.4, +51.9, and +22.0%). BPNDs of the caudate nucleus and putamen showed significant differences (P= 0.0472 and 0.0221) after placebo, low-dose glucose, and high-dose glucose loading. BPNDs in the caudate nucleus and putamen after placebo, low-dose glucose, and high-dose glucose loading were positively intercorrelated with each other. In conclusion, striatal DAT changes after physiological glucose loading, but not after supraphysiological glucose loading in humans. DAT availabilities after placebo, low-dose glucose, high-dose glucose loading were correlated to each other in the caudate nucleus and putamen, but not in the VST. Therefore, sub-regional variability in DAT regulatory mechanisms mediated by insulin may exist in humans.

Photodynamic therapy (PDT) is an effective anticancer strategy with a higher selectivity and fewer adverse effects than conventional therapies; however, shallow tissue penetration depth of light has hampered the clinical utility of PDT. Recently, reports have indicated that Cerenkov luminescence-induced PDT may overcome the tissue penetration limitation of conventional PDT. However, the effectiveness of this method is controversial because of its low luminescence intensity. Herein, we developed a radiolabeled diethylenetriaminepentaacetic acid chelated Eu3+(Eu-DTPA)/photosensitizer (PS) loaded liposome (Eu/PS-lipo) that utilizes ionizing radiation from radioisotopes for effective in vivoimaging and radioluminescence-induced PDT. We utilized Victoria blue-BO (VBBO) as a PS and observed an efficient luminescence resonance energy transfer between Eu-DTPA and VBBO. Furthermore, 64Cu-labeled Eu lipo demonstrated a strong radioluminescence with a 2-fold higher intensity than Cerenkov luminescence from free 64Cu. In our radioluminescence liposome, radioluminescence energy transfer showed a 6-fold higher energy transfer efficiency to VBBO than Cerenkov luminescence energy transfer (CLET). 64Cu-labeled Eu/VBBO lipo (64Cu-Eu/VBBO lipo) showed a substantial tumor uptake of up to 19.3%ID/g by enhanced permeability and retention effects, as revealed by in vivopositron emission tomography. Finally, the PDT using 64Cu-Eu/VBBO lipo demonstrated significantly higher in vitroand in vivotherapeutic effects than Cerenkov luminescence-induced PDT using 64Cu-VBBO lipo. This study envisions a great opportunity for clinical PDT application by establishing the radioluminescence liposome which has high tumor targeting and efficient energy transfer capability from radioisotopes.

Supplemental digital content is available in the text.

Liposome is one of the oldest yet most successful nanomedicine platforms. Doxil®, PEGylated liposome loaded with doxorubicin (DOX), was approved by the FDA in 1995 for the treatment of AIDS-related Kaposi’s sarcoma, and it was the first approval for nanomedicine. Since then, liposome-based therapeutics were approved for the treatment of various diseases and many clinical trials are underway. The success of the liposome-based therapeutics was due to following factors: (1) ease of synthesis, (2) biocompatibility, (3) the ability to load both hydrophilic and hydrophobic agents, and (4) long circulation property after application of polyethylene glycol (PEG). Recently, more functionalities are introduced to liposome platform, which are (1) in vivo imaging probes for optical, magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT), (2) pH and temperature-sensitive lipid moiety, and (3) novel agents for photodynamic and photothermal therapies (PDT, PTT). These conventional and newly tested advantages make the liposome to be one of the most promising nanoplatforms for theranostics.

Technetium-99m-labeled human serum albumin (99mTc-HSA) has been utilized as a blood pool imaging agent in the clinic for several decades. However, 99mTc-HSA has a short circulation time, which is a critical shortcoming for a blood pool imaging agent. Herein, we developed a novel 99mTc-labeled HSA with a long circulation time using click chemistry and a chelator, 2,2′-dipicolylamine (DPA), (99mTc-DPA-HSA). Specifically, we examined the feasibility of copper-free strain-promoted alkyne-azide cycloaddition (SPAAC) for the incorporation of HSA to the [99mTc (CO)3(H2O)3]+system by adopting a chelate-then-click approach. In this strategy, a potent chelate system, azide-functionalized DPA, was first complexed with [99mTc (CO)3(H2O)3]+, followed by the SPAAC click reaction with azadibenzocyclooctyne-functionalized HSA (ADIBO–HSA) under biocompatible conditions. Radiolabeling efficiency of azide-functionalized DPA (99mTc-DPA) was >98%. Click conjugation efficiency of 99mTc-DPA with ADIBO–HSA was between 76 and 99% depending on the number of ADIBO moieties attached to HSA. In whole-body in vivo single photon emission computed tomography images, the blood pool uptakes of 99mTc-DPA-HSA were significantly enhanced compared to those of 99mTc-HSA at 10 min, 2, and 6 h after the injection (P< 0.001, 0.025, and 0.003, respectively). Furthermore, the blood activities of 99mTc-DPA-HSA were 8 times higher at 30 min and 10 times higher at 3 h after the injection compared to those of conventional 99mTc-HSA in ex vivo biodistribution experiment. The results exhibit the potential of 99mTc-DPA-HSA as a blood pool imaging agent and further illustrate the promise of the pre-labeling SPAAC approach for conjugation of heat-sensitive biological targeting vectors with [99mTc (CO)3(H2O)3]+.

Single-point FDG PET/CT scan either at baseline, interim, or posttherapy was predictive of event-free and overall survival even after adjusting for histologic response and initial presence of metastasis.

Numerous methods to segment tumors using 18F-fluorodeoxyglucose positron emission tomography (FDG PET) have been introduced. Metabolic tumor volume (MTV) refers to the metabolically active volume of the tumor segmented using FDG PET, and has been shown to be useful in predicting patient outcome and in assessing treatment response. Also, tumor segmentation using FDG PET has useful applications in radiotherapy treatment planning. Despite extensive research on MTV showing promising results, MTV is not used in standard clinical practice yet, mainly because there is no consensus on the optimal method to segment tumors in FDG PET images. In this review, we discuss currently available methods to measure MTV using FDG PET, and assess the advantages and disadvantages of the methods.

Peripheral arterial disease (PAD) is a leading global health concern. Due to limited imaging and therapeutic options, PAD and other ischemia-related diseases may benefit from the use of long circulating nanoparticles as imaging probes and/or drug delivery vehicles. Polyethylene glycol (PEG)-conjugated nanoparticles have shown shortened circulation half-lives in vivowhen injected multiple times into a single subject. This phenomenon has become known as the accelerated blood clearance (ABC) effect. The phenomenon is of concern for clinical translation of nanomaterials as it limits the passive accumulation of nanoparticles in many diseases, yet it has not been evaluated using inorganic or organic–inorganic hybrid nanoparticles. Herein, we found that the ABC phenomenon was induced by reinjection of PEGylated long circulating organic–inorganic hybrid nanoparticles, which significantly reduced the passive targeting of 64Cu-labeled PEGylated reduced graphene oxide–iron oxide nanoparticles (64Cu-RGO-IONP-PEG) in a murine model of PAD. Positron emission tomography (PET) imaging was performed at 3, 10, and 17 days postsurgical induction of hindlimb ischemia. At day 3 postsurgery, the nanoparticles displayed a long circulation half-life with enhanced accumulation in the ischemic hindlimb. At days 10 and 17 postsurgery, reinjected mice displayed a short circulation half-life and lower accumulation of the nanoparticles in the ischemic hindlimb, in comparison to the naïve group. Also, reinjected mice showed significantly higher liver uptake than the naïve group, indicating that the nanoparticles experienced higher sequestration by the liver in the reinjected group. Furthermore, photoacoustic (PA) imaging and Prussian blue staining confirmed the enhanced accumulation of the nanoparticles in the liver tissue of reinjected mice. These findings validate the ABC phenomenon using long circulating organic–inorganic hybrid nanoparticles upon multiple administrations to the same animal, which may provide valuable insight into the future clinical applications of nanoparticles for imaging and treatment of PAD.

The role of insulin-like growth factor-1 receptor (IGF-1R) in cancer tumorigenesis was established decades ago, yet there are limited studies evaluating the imaging and therapeutic properties of anti-IGF-1R antibodies. Noninvasive imaging of IGF-1R may allow for optimized patient stratification and monitoring of therapeutic response in patients. Herein, this study reports the development of a Zirconium-89 (89Zr)-labeled anti-IGF-1R antibody (89Zr-Df-1A2G11) for PET imaging of pancreatic cancer. Successful chelation and radiolabeling of the antibody resulted in a highly stable construct that could be used for imaging IGF-1R expressing tumors in vivo. Western blot and flow cytometry studies showed that MIA PaCa-2, BxPC-3, and AsPC-1 pancreatic cancer cell lines expressed high, moderate, and low levels of IGF-1R, respectively. These three pancreatic cancer cell lines were subcutaneously implanted into mice. By employing the PET imaging technique, the tumor accumulation of 89Zr-Df-1A2G11 was found to be dependent on the level of IGF-1R expression. Tumor accumulation of 89Zr-Df-1A2G11 was 8.24 ± 0.51, 5.80 ± 0.54, and 4.30 ± 0.42 percentage of the injected dose (%ID/g) in MIA PaCa-2, BxPC-3, and AsPC-1-derived tumor models at 120 h postinjection, respectively (n= 4). Biodistribution studies and ex vivo immunohistochemistry confirmed these findings. In addition, 89Zr-labeled nonspecific human IgG (89Zr-Df-IgG) displayed minimal uptake in IGF-1R positive MIA PaCa-2 tumor xenografts (3.63 ± 0.95%ID/g at 120 h postinjection; n= 4), demonstrating that 89Zr-Df-1A2G11 accumulation was highly specific. This study provides initial evidence that our 89Zr-labeled IGF-1R-targeted antibody may be employed for imaging a wide range of malignancies. Antibodies may be tracked in vivo for several days to weeks with 89Zr, which may enhance image contrast due to decreased background signal. In addition, the principles outlined in this study can be employed for identifying patients that may benefit from anti-IGF-1R therapy.

Supplemental digital content is available in the text.

In parathyroid adenoma, uptake of technetium-99m-methoxyisobutylisonitrile (99mTc-MIBI) has been suggested to have a correlation with functional markers. The purpose of this study was to evaluate the feasibility of 99mTc-MIBI parathyroid single photon emission computed tomographycomputed tomography (SPECTCT) in evaluating the function and disease severity of parathyroid adenoma.

Lymph node involvement in cervical cancer is an indication of poor prognosis and the risk tends to increase according to the level of lymph node involvement. However, the specific prognostic significance of retrocrural lymph node involvement has not been well characterized because of its small size and deep location. The aim of this study was to assess its prognostic value.

Lymph node (LN) characterization is crucial in determining the stage and treatment decisions in patient with lung cancer. Although 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has a higher diagnostic accuracy in LN characterization than anatomical imaging, differentiating between metastatic and inflammatory LNs is still challenging because both could show high 18F-FDG uptake. The purpose of this study was to assess if the heterogeneity of the 18F-FDG uptake could help in differentiating between inflammatory and metastatic LNs in lung cancer, and to compare with other parameters. A total of 44 patients with adenocarcinoma of the lung, who underwent preoperative 18F-FDG PET/CT without having any previous treatments and were revealed to have 18F-FDG-avid LNs, were enrolled. There were 52 pathology-proven metastatic lymph nodes in 26 subjects. The pathology-proven metastatic LNs were compared with 42 pathology-proven inflammatory/benign LNs in 18 subjects. The coefficient of variation (CV) was used to assess the heterogeneity of 18F-FDG uptake by dividing the standard deviation of standardized uptake value (SUV) by mean SUV. The volume of interest was manually drawn based on the combined CT images of 18F-FDG PET/CT (no threshold is used). Comparisons were made with the maximum standardized uptake values (SUVmax), visual assessment of 18F-FDG uptake, longest diameter, and maximum Hounsfield units (HUmax). Metastatic lymph nodes tended to have higher CVs than the inflammatory LNs. The mean CV of metastatic LNs (0.30 ± 0.08; range: 0.08–0.55) was higher than that of inflammatory LNs (0.17 + 0.06; range, 0.07–0.32; P< 0.0001). On receiver operating characteristic (ROC) curve analysis, the area under curve was 0.901, and using 0.20 as cut-off value, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 88.5 %, 76.2 %, 82.2 %, 84.3, and 83.0 % respectively. Accuracy of CV was slightly higher than SUVmax and diameter, but significantly higher than visual assessment and HUmax. In patients with adenocarcinoma of the lung having no prior treatments, metastatic LNs showed more heterogeneous 18F-FDG uptake than inflammatory LNs. Measuring the CV of the SUV derived from a manual volume of interest (VOI) can be helpful in determining metastatic LN of adenocarcinoma of the lung. Including diagnostic criteria of CV into the diagnostic approach can increase the accuracy of mediastinal node status.

The purpose of this study was to investigate the usefulness of metabolic-volumetric indices of 18F- fluorodeoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for the evaluation of neoadjuvant chemotherapy outcomes in breast cancer.Twenty-four patients with locally advanced breast cancer were enrolled in the study. They underwent baseline 18F-FDG PET/CT scan and received four or six cycles of neoadjuvant chemotherapy, interim 18F-FDG PET/CT was done after second cycle of chemotherapy. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary lesions were calculated. Reduction rates of these parameters were obtained between baseline and interim 18F-FDG PET/CT. Chemotherapy outcomes were assessed using tumor size reduction rate and histological grading system (Miller and Payne system). Reduction rates of SUVmax, MTV, and TLG correlated with chemotherapy outcomes.MTV and TLG reduction rates showed significant correlation with tumor size reduction rate (R= 0.68, P= 0.0004; R = 0.62, P= 0.002, respectively). However, SUVmax reduction rate showed no significant correlation. MTV and TLG reduction rates were significantly higher in responders than nonresponders, as determined by Miller and Payne system (P< 0.0007, P< 0.002). However, SUVmax reduction rate showed no significant difference. On ROC analysis, the area under the MTV and TLG curves was 0.886, and that of SUVmax was 0.743. Sensitivity, specificity, positive predictive value, and negative predictive value to predict histopathologic response were the same for MTV and TLG, and the values were 100 %, 85.7 %, 83.3 %, and 100 %, respectively (at the reduction rate of 93.2 % for MTV, and 95.8 % for TLG).Changes of metabolic–volumetric indices successfully reflected the neoadjuvant chemotherapy outcomes. MTV and TLG could be robust indices in discriminating pathologic responder as SUVmax, after neoadjuvant chemotherapy.

18F-FP-CIT positron emission tomography (PET) is an effective imaging for dopamine transporters. In usual clinical practice, 18F-FP-CIT PET is analyzed visually or quantified using manual delineation of a volume of interest (VOI) for the striatum. In this study, we suggested and validated two simple quantitative methods based on automatic VOI delineation using statistical probabilistic anatomical mapping (SPAM) and isocontour margin setting.Seventy-five 18F-FP-CIT PET images acquired in routine clinical practice were used for this study. A study-specific image template was made and the subject images were normalized to the template. Afterwards, uptakes in the striatal regions and cerebellum were quantified using probabilistic VOI based on SPAM. A quantitative parameter, QSPAM, was calculated to simulate binding potential. Additionally, the functional volume of each striatal region and its uptake were measured in automatically delineated VOI using isocontour margin setting. Uptake-volume product (QUVP) was calculated for each striatal region. QSPAMand QUVPwere compared with visual grading and the influence of cerebral atrophy on the measurements was tested.Image analyses were successful in all the cases. Both the QSPAMand QUVPwere significantly different according to visual grading (P< 0.001). The agreements of QUVPor QSPAMwith visual grading were slight to fair for the caudate nucleus (κ = 0.421 and 0.291, respectively) and good to perfect to the putamen (κ = 0.663 and 0.607, respectively). Also, QSPAMand QUVPhad a significant correlation with each other (P< 0.001). Cerebral atrophy made a significant difference in QSPAMand QUVPof the caudate nuclei regions with decreased 18F-FP-CIT uptake.Simple quantitative measurements of QSPAMand QUVPshowed acceptable agreement with visual grading. Although QSPAMin some group may be influenced by cerebral atrophy, these simple methods are expected to be effective in the quantitative analysis of 18F-FP-CIT PET in usual clinical practice.

Abstract: Purpose: Retrocrural lymph nodes (RCLNs) communicate with retroperitoneal and posterior mediastinal LNs. It is possible that, when RCLNs are involved, supra-diaphragmatic extension will occur in abdomino-pelvic cancers. The authors investigated performance of 18F-FDG PET/CT to diagnose RCLN metastasis and whether RCLN metastases were associated with supra-diaphragmatic lymphatic metastases of ovarian cancer. Materials and methods: Sixty-seven patients with stage IV ovarian cancer who had undergone 18F-FDG PET/CT were included in this retrospective study. Diagnostic performance of 18F-FDG PET/CT for RCLN metastasis was evaluated. Patients were divided into two groups by presence or absence of supra-diaphragmatic LN metastasis. The prevalences of RCLN metastasis between the two groups were compared and the odds ratio was calculated. Results: Sensitivity and specificity of 18F-FDG PET/CT for RCLN metastasis were 96.3 and 100%, respectively. Of the 67 study subjects, 27 patients had RCLN metastases (40.3%). Fifty patients had supra-diaphragmatic LN metastases. 18F-FDG PET/CT showed 26 RCLN metastases in patients with supra-diaphragmatic LN metastases (54.5%), and only 1 in patients without supra-diaphragmatic LN metastasis (5.9%), and the difference between two groups was statistically significant (P < 0.05). The odds ratio that patients with RCLN metastasis would have supra-diaphragmatic LN metastasis was 17.3 (95% confidence interval = 2.1 to 140.9, P = 0.008). Conclusion: Performance of 18F-FDG PET/CT to diagnose RCLN metastasis was excellent. RCLN metastasis revealed by 18F-FDG PET/CT was strongly associated with supra-diaphragmatic LN spread of ovarian cancer. Thus, RCLN metastasis could be used as a predictor of supra-diaphragmatic lymphatic metastasis of ovarian cancer.

Abstract: The expression of glucose transporters (Glut-1, Glut-3), hexokinase-II, and Ki-67 has been proposed to explain intratumoral heterogeneous F-18 fluorodeoxyglucose (FDG) uptake. We report a case of Krukenberg tumor with intratumoral heterogeneous FDG uptake which corresponded well with the expression levels of Glut-1 and ki-67. Fused positron emission tomography (PET)/magnetic resonance (MR) imaging was helpful for localizing the metabolically active area in the tumor specimen. This report elucidates the relationship between the intratumoral heterogeneous FDG uptake and biologic heterogeneity, and shows the usefulness of PET/MR in research on intratumoral heterogeneity.

We developed hybrid nanospheres comprised of two of the most important biomolecules in nature, DNA and proteins, which have excellent biocompatibility, high drug payload capacity, in vivoimaging ability, and in vitro/in vivocancer targeting capability. The synthesis can be done in a facile one-pot assembly system that includes three steps: step-growth polymerization of two DNA oligomers, addition of streptavidin to assemble spherical hybrid nanostructures, and functionalization of hybrid nanospheres with biotinylated aptamers. To test the feasibility of cancer targeting and drug-loading capacity of the hybrid nanospheres, MUC1-specific aptamers (MA3) were conjugated to nanosphere surfaces (apt-nanospheres), and doxorubicin (Dox) was loaded into nanospheres by DNA intercalation. The successful construction of nanospheres and apt-nanospheres was confirmed by agarose gel electrophoresis and dynamic light scattering (DLS). Their uniform spherical morphology was confirmed by transmission electron microscopy (TEM). Fluorescence spectra of nanospheres demonstrated high Dox-loading capability and slow-release characteristics. In vitroMUC1-specific binding of the apt-nanospheres was confirmed by flow cytometry and confocal microscopy. Dox-loaded apt-nanospheres significantly increased cytotoxicity of the MUC1-positive cancer cells due to aptamer-mediated selective internalization, as shown via cell viability assays. Apt-nanospheres could also be imaged in vivothrough the synthesis of hybrid nanospheres using fluorescent dye-conjugated DNA strands. Finally, in vivospecific targeting ability of apt-nanospheres was confirmed in a MUC1-positive 4T1 tumor-bearing mouse model, whereas apt-nanospheres did not cause any sign of systemic toxicity in normal mice. Taken together, our self-assembled DNA–streptavidin hybrid nanospheres show promise as a biocompatible cancer targeting material for contemporary nanomedical technology.

Acute kidney injury (AKI) leads to unacceptably high mortality due to difficulties in timely intervention and less efficient renal delivery of therapeutic drugs. Here, a series of polyvinylpyrrolidone (PVP)-curcumin nanoparticles (PCurNP) are designed to meet the renal excretion threshold (∼45 kDa), presenting a controllable delivery nanosystem for kidney targeting. Renal accumulation of the relatively small nanoparticles, 89Zr-PCurNP M10 with the diameter between 5-8 nm, is found to be 1.7 times and 1.8 times higher than the accumulation of 89Zr-PCurNP M29 (20–50 nm) and M40 (20–50 nm) as revealed by PET imaging. Furthermore, serum creatinine analysis, kidney tissues histology, and tubular injury scores revealed that PCurNP M10 efficiently treated cisplatin-induced AKI. Herein, PCurNP offers a novel and simple strategy for precise PET image-guided drug delivery of renal protective materials.