Effective Treatment of Disseminated Prostate Cancer Using CD46-Targeted 225Ac Therapy Anil P. Bidkar, Robin Peter, Anju Wadhwa, Kondapa Naidu Bobba, Scott Bidlingmaier, et al. Clinical Cancer Research, 2025 Purpose: Metastatic castration-resistant prostate cancer has limited treatment options and a poor prognosis. Recently, prostate-specific membrane antigen (PSMA)-targeted alpha-particle therapy agents using actinium-225 (225Ac) have shown promising results in prostate cancer treatment, but a significant fraction of patients with advanced mCRPC demonstrate loss of PSMA expression. We have previously reported that PSMA-null and PSMA-positive tumors can be detected and treated effectively with CD46-targeted radiopharmaceuticals. This study evaluates the CD46-targeting PET imaging agent [89Zr]DFO-YS5, and the radioimmunotherapy agent [225Ac]Macropa-PEG4-YS5, in disseminated prostate cancer tumors. Experimental Design: Microtumor lesions, primarily observed in the liver, kidneys, and lungs, were successfully detected with [89Zr]DFO-YS5 PET imaging. We used disseminated 22Rv1 tumors for biodistribution studies, dosimetry assessments, and therapeutic efficacy evaluations of [225Ac]Macropa-PEG4-YS5. Results: Quantitative digital alpha-particle autoradiography revealed high radiation dose deposition from [225Ac]Macropa-PEG4-YS5 in microtumors compared with surrounding liver tissues, although in larger lesions (>1 mm diameter), the dose distribution was heterogeneous. Early treatment of smaller disseminated tumors with a uniform radiation dose was more effective in ablating tumors and promoting survival. In late-stage lesions of large size, heterogeneous dose deposition limited therapeutic efficacy, requiring higher administered activity to achieve a complete response. Conclusions: Our findings highlight that [225Ac]Macropa-PEG4-YS5 holds the potential for clinical translation for metastatic prostate cancer and reinforces the value of microdosimetry in understanding the efficacy of and resistance to targeted alpha therapy. See related commentary by Patel et al., p. 2847
Fibroblast Activation Protein as a Molecular Handle in Cancer Phototheranostics: Recent Advances Sangramjit Basak, Subhadarshini Satapathy, Anitya Shukla, Nidhi Srivastava, Niranjan Meher Molecular Pharmaceutics, 2025 Fibroblast activation protein (FAP) is a type II transmembrane serine protease that is selectively overexpressed in the tumor microenvironment (TME) of various cancer phenotypes, making it a promising target for personalized cancer therapy. Unlike other broadly expressed surface proteins, FAP is predominantly found in cancer-associated fibroblasts (CAFs), where it plays a crucial role in tumor progression. This selective expression enables targeted therapeutic interventions with minimal off-target toxicity. Conventional and some advanced cancer treatment modalities are often associated with significant background toxicity, which can be mitigated by secondary treatment strategies such as phototherapy. This review provides a comprehensive overview of the latest developments in FAP-targeted phototheranostic probes, including small molecules, peptides, and antibodies. Special emphasis is given to advancements in near-infrared (NIR)-based phototherapeutic probes, highlighting their improved imaging and therapeutic efficacy through enhanced tissue penetration.
Dual Targeting of Prostate-Specific Membrane Antigen and Fibroblast Activation Protein: Bridging Prostate Cancer Theranostics with Precision Boga Vijay Kumar, Riya Sachan, Prajakta Garad, Nidhi Srivastava, Shubhini A. Saraf, Niranjan Meher ACS Applied Bio Materials, 2025 Targeting Prostate Specific Membrane Antigen (PSMA) has proven highly useful and beneficial for prostate cancer (PCa) theranostics. However, patients with advanced metastatic castration-resistant prostate cancer (mCRPC) lack optimal PSMA expression resulting in poor specificity. To address this limitation, combination targeting is gaining popularity by synergistically boosting the theranostic efficacy. Herein, we thoroughly reviewed the most recent development of drug formulation for PCa theranostics by targeting both PSMA and Fibroblast Activation Protein (FAP). FAP is known to overexpress in cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME). It has been extensively studied as an effective target for the identification and treatment of a variety of cancer phenotypes. Along with the advantages and current updates on combination targeting of PSMA and FAP, this Review thoroughly discussed the expression patterns of PSMA and FAP in various cancer phenotypes, as well as their role in tumor growth, invasion, and metastasis, which is of great interest in the design and development of prostate cancer theranostics.
PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer Niranjan Meher, Anil P. Bidkar, Anju Wadhwa, Kondapa Naidu Bobba, Suchi Dhrona, Chandrashekhar Dasari, Changhua Mu, Cyril O.Y. Fong, Juan A. Cámara, Umama Ali, Megha Basak, David Bulkley, Veronica Steri, Shaun D. Fontaine, Jun Zhu, Adam Oskowitz, Rahul R. Aggarwal, Renuka Sriram, Jonathan Chou, David M. Wilson, Youngho Seo, Daniel V. Santi, Gary W. Ashley, Henry F. VanBrocklin, Robert R. Flavell Molecular Cancer Therapeutics, 2025 The enhanced permeability and retention (EPR) effect controls passive nanodrug uptake in tumors and may provide a high tumor payload with prolonged retention for cancer treatment. However, EPR-mediated tumor uptake and distribution vary by cancer phenotype. Thus, we hypothesized that a companion PET imaging surrogate may benefit EPR-mediated therapeutic drug delivery. We developed two 89Zr-radiolabeled nanocarriers based on 4-armed starPEG40kDa with or without talazoparib (TLZ), a potent PARP inhibitor, as surrogates for the PEG-TLZ4 therapeutic scaffold. For PET imaging, PEG-DFB4 and PEG-DFB1-TLZ3 were radiolabeled with 89Zr by replacing one or all four copis of TLZ on PEG-TLZ4 with deferoxamine B (DFB). The radiolabeled nanodrugs [89Zr]PEG-DFB4 and [89Zr]PEG-DFB1-TLZ3 were tested in vivo in prostate cancer subcutaneous (s.c.) xenografts (22Rv1, LTL-545, and LTL-610) and 22Rv1 metastatic models. Their EPR-mediated tumoral uptake and penetration was compared with CT26, a known EPR-high cell line. MicroPET/CT images, organ biodistribution, and calculated kinetic parameters showed high uptake in CT26 and LTL-545 and moderate to low uptake in LTL-610 and 22Rv1. MicroPET/CT and high-resolution autoradiographic images showed nanocarrier penetration into highly permeable CT26, but heterogeneous peripheral accumulation was observed in LTL-545, LTL-610, and 22Rv1 s.c. xenografts and metastatic tumors. CD31 staining of tumor sections showed homogenous vascular development in CT26 tumors and heterogeneity in other xenografts. Both [89Zr]PEG-DFB4 and [89Zr]PEG-DFB1-TLZ3 showed similar accumulation and distribution in s.c. and metastatic tumor models. Both nanocarriers can measure tumor model passive uptake heterogeneity. Although heterogeneous, prostate cancer xenografts had low EPR. These starPEG nanocarriers could be used as PET imaging surrogates to predict drug delivery and efficacy.
PLX038A, a long-acting SN-38, penetrates the blood-tumor-brain-barrier, accumulates and releases SN-38 in brain tumors to increase survival of tumor bearing mice Jinkyu Jung, Eric L. Schneider, Wei Zhang, Hua Song, Meili Zhang, William Chou, Niranjan Meher, Henry F. VanBrocklin, Mary Helen Barcellos-Hoff, Tomoko Ozawa, Mark R. Gilbert, Daniel V. Santi Scientific Reports, 2024 Central nervous system tumors have resisted effective chemotherapy because most therapeutics do not penetrate the blood-tumor-brain-barrier. Nanomedicines between ~ 10 and 100 nm accumulate in many solid tumors by the enhanced permeability and retention effect, but it is controversial whether the effect can be exploited for treatment of brain tumors. PLX038A is a long-acting prodrug of the topoisomerase 1 inhibitor SN-38. It is composed of a 15 nm 4-arm 40 kDa PEG tethered to four SN-38 moieties by linkers that slowly cleave to release the SN-38. The prodrug was remarkably effective at suppressing growth of intracranial breast cancer and glioblastoma (GBM), significantly increasing the life span of mice harboring them. We addressed the important issue of whether the prodrug releases SN-38 systemically and then penetrates the brain to exert anti-tumor effects, or whether it directly penetrates the blood-tumor-brain-barrier and releases the SN-38 cargo within the tumor. We argue that the amount of SN-38 formed systemically is insufficient to inhibit the tumors, and show by PET imaging that a close surrogate of the 40 kDa PEG carrier in PLX038A accumulates and is retained in the GBM. We conclude that the prodrug penetrates the blood-tumor-brain-barrier, accumulates in the tumor microenvironment and releases its SN-38 cargo from within. Based on our results, we pose the provocative question as to whether the 40 kDa nanomolecule PEG carrier might serve as a “Trojan horse” to carry other drugs past the blood-tumor-brain-barrier and release them into brain tumors.
Prostate-Specific Membrane Antigen Targeted StarPEG Nanocarrier for Imaging and Therapy of Prostate Cancer Niranjan Meher, Gary W. Ashley, Kondapa Naidu Bobba, Anju Wadhwa, Anil P. Bidkar, Chandrashekhar Dasari, Changhua Mu, Ramya Ambur Sankaranarayanan, Juan A. Camara Serrano, Athira Raveendran, David P. Bulkley, Rahul Aggarwal, Nancy Y. Greenland, Adam Oskowitz, David M. Wilson, Youngho Seo, Daniel V. Santi, Henry F. VanBrocklin, Robert R. Flavell Advanced Healthcare Materials, 2024
CD46-Targeted Theranostics for PET and 225Ac-Radiopharmaceutical Therapy of Multiple Myeloma Anju Wadhwa, Sinan Wang, Bonell Patiño-Escobar, Anil P. Bidkar, Kondapa Naidu Bobba, Emily Chan, Niranjan Meher, Scott Bidlingmaier, Yang Su, Suchi Dhrona, Huimin Geng, Vishesh Sarin, Henry F. VanBrocklin, David M. Wilson, Jiang He, Li Zhang, Veronica Steri, Sandy W. Wong, Thomas G. Martin, Youngho Seo, Bin Liu, Arun P. Wiita, Robert R. Flavell Clinical Cancer Research, 2024
Treatment of Prostate Cancer with CD46-targeted 225Ac Alpha Particle Radioimmunotherapy Anil P. Bidkar, Sinan Wang, Kondapa Naidu Bobba, Emily Chan, Scott Bidlingmaier, Emily A. Egusa, Robin Peter, Umama Ali, Niranjan Meher, Anju Wadhwa, Suchi Dhrona, Chandrashekhar Dasari, Denis Beckford-Vera, Yang Su, Ryan Tang, Li Zhang, Jiang He, David M. Wilson, Rahul Aggarwal, Henry F. VanBrocklin, Youngho Seo, Jonathan Chou, Bin Liu, Robert R. Flavell Clinical Cancer Research, 2023
Prostate-specific membrane antigen targeted deep-tumor penetration of polymer nanodrugs and methods of use thereof R FLAVELL, H VANBROCKLIN, N Meher, GW Ashley, DV Santi US Patent App. 19/107,004 , 2026 2026
Unmasking the role of tumor microenvironment in the advanced stage of cancer treatment to mitigate risks during chemotherapy A Kumari, N Meher, A Dey, S Awasthi, SA Saraf, N Srivastava Biochemical Pharmacology, 117754 , 2026 2026
Development of 18F-labelled Zinc Biosensors and PET Imaging U Ali, C Mu, J Blecha, A Wadhwa, N Meher, A Bidkar, S Wang, Y Seo, ... Nuclear Medicine and Biology 148, 109082 , 2025 2025
Voices in Molecular Pharmaceutics: Meet Dr. Niranjan Meher who Designs Light-Activated Intelligent Drug Delivery Systems N Meher Molecular Pharmaceutics 22 (8), 4335-4336 , 2025 2025
Effective Treatment of Disseminated Prostate Cancer Using CD46-Targeted 225 Ac Therapy AP Bidkar, R Peter, A Wadhwa, KN Bobba, S Bidlingmaier, N Meher, ... Clinical Cancer Research 31 (14), 2963-2977 , 2025 2025 Citations: 10
Fibroblast activation protein as a molecular handle in cancer phototheranostics: recent advances S Basak, S Satapathy, A Shukla, N Srivastava, N Meher Molecular pharmaceutics 22 (7), 3621-3636 , 2025 2025 Citations: 4
Dual targeting of prostate-specific membrane antigen and fibroblast activation protein: Bridging prostate cancer theranostics with precision BV Kumar, R Sachan, P Garad, N Srivastava, SA Saraf, N Meher ACS Applied Bio Materials 8 (2), 962-979 , 2025 2025 Citations: 3
PET Imaging Using 89 Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer N Meher, AP Bidkar, A Wadhwa, KN Bobba, S Dhrona, C Dasari, C Mu, ... Molecular Cancer Therapeutics 24 (1), 141-151 , 2025 2025 Citations: 16
Antibody drug conjugates integrated with lipid nanocarrier for cancer theranostics BV Kumar, A Shukla, N Ahmed, K Solanki, N Srivastava, SA Saraf, ... Lipid-Drug Conjugates, 333-363 , 2025 2025
Mechanistic investigation on cellular internalization triggering structure-induced conformational modulation of boron–nitrogen luminogens R Parui, H Roy, N Meher, SS Ghosh, PK Iyer Chemical science 16 (14), 6023-6034 , 2025 2025
Non-conjugated alkyl chain engineering to tune condensed state photophysical and supramolecular assembly properties N Meher, MN Khatun, R Parui, PK Iyer Nanoscale 17 (11), 6685-6694 , 2025 2025 Citations: 2
Prostate-specific membrane antigen-targeted NIR phototheranostics for prostate cancer K Solanki, N Ahmed, N Srivastava, N Meher ACS Applied Bio Materials 7 (9), 5861-5884 , 2024 2024 Citations: 20
3D small-scale dosimetry and tumor control of 225 Ac radiopharmaceuticals for prostate cancer R Peter, AP Bidkar, KN Bobba, L Zerefa, C Dasari, N Meher, A Wadhwa, ... Scientific Reports 14 (1), 19938 , 2024 2024 Citations: 15
Prostate‐Specific Membrane Antigen Targeted StarPEG Nanocarrier for Imaging and Therapy of Prostate Cancer N Meher, GW Ashley, KN Bobba, A Wadhwa, AP Bidkar, C Dasari, C Mu, ... Advanced healthcare materials 13 (19), 2304618 , 2024 2024 Citations: 10
Enhanced prostate-specific membrane antigen targeting by precision control of DNA scaffolded nanoparticle ligand presentation D Jana, Z Han, X Huang, A Wadhwa, A Raveendran, K Ebeid, N Meher, ... ACS nano 18 (26), 16674-16683 , 2024 2024 Citations: 18
PLX038A, a long-acting SN-38, penetrates the blood-tumor-brain-barrier, accumulates and releases SN-38 in brain tumors to increase survival of tumor bearing mice J Jung, EL Schneider, W Zhang, H Song, M Zhang, W Chou, N Meher, ... Scientific Reports 14 (1), 14175 , 2024 2024 Citations: 3
Evaluation of 225Ac/134Ce-Macropa-PEG4-YS5 as a novel theranostic pair for prostate cancer therapy K Bobba, A Bidkar, A Wadhwa, N Meher, S Drona, S Bidlingmaier, ... Journal of Nuclear Medicine 65 (supplement 2), 242306-242306 , 2024 2024
CD46 targeted alpha particle therapy for the treatment of metastatic prostate cancer tumor models A Bidkar, A Wadhwa, K Bobba, R Peter, N Meher, S Bidlingmaier, ... Journal of Nuclear Medicine 65 (supplement 2), 242182-242182 , 2024 2024
StarPEG nanocarriers: A versatile nanoplatform for tumor imaging and therapy N Meher, G Ashley, A Wadhwa, K Bobba, A Bidkar, C Dasari, C Mu, ... Journal of Nuclear Medicine 65 (supplement 2), 241764-241764 , 2024 2024
CD46-Targeted Theranostics for PET and 225 Ac-Radiopharmaceutical Therapy of Multiple Myeloma A Wadhwa, S Wang, B Patino-Escobar, AP Bidkar, KN Bobba, E Chan, ... Clinical Cancer Research 30 (5), 1009-1021 , 2024 2024 Citations: 20
MOST CITED SCHOLAR PUBLICATIONS
Functional 1,8-Naphthalimide AIE/AIEEgens: Recent Advances and Prospects P Gopikrishna, N Meher, PK Iyer ACS applied materials & interfaces 10 (15), 12081–12111 , 2017 2017 Citations: 351
Aldehyde group driven aggregation-induced enhanced emission in naphthalimides and its application for ultradetection of hydrazine on multiple platforms N Meher, S Panda, S Kumar, PK Iyer Chemical Science 9 (16), 3978-3985 , 2018 2018 Citations: 130
Spontaneously Self‐assembled Naphthalimide Nanosheets: Aggregation Induced Emission and Unveiling a‐PET for Sensitive Detection of Organic Volatile Contaminants in Water N Meher, PK Iyer Angewandte Chemie , 2018 2018 Citations: 117
Recent development of the fluorescence-based detection of volatile organic compounds: a mechanistic overview N Meher, D Barman, R Parui, PK Iyer Journal of Materials Chemistry C 10 (28), 10224-10254 , 2022 2022 Citations: 82
Stepwise elucidation of fluorescence based sensing mechanisms considering picric acid as a model analyte AS Tanwar, N Meher, LR Adil, PK Iyer Analyst 145 (14), 4753-4767 , 2020 2020 Citations: 66
Treatment of Prostate Cancer with CD46-targeted 225 Ac Alpha Particle Radioimmunotherapy AP Bidkar, S Wang, KN Bobba, E Chan, S Bidlingmaier, EA Egusa, ... Clinical Cancer Research 29 (10), 1916-1928 , 2023 2023 Citations: 64
Pendant chain engineering to fine-tune the nanomorphologies and solid state luminescence of naphthalimide AIEEgens: Application to phenolic nitro-explosive detection in water N Meher, PK Iyer Nanoscale 9 (22), 7674-7685 , 2017 2017 Citations: 58
Aggregation induced emission enhancement and growth of naphthalimide nanoribbons via J-aggregation: insight into disaggregation induced unfolding and detection of ferritin at … N Meher, SR Chowdhury, PK Iyer Journal of Materials Chemistry B 4 (36), 6023-6031 , 2016 2016 Citations: 54
Condition Assessment of Aged Ester based Nanofluid Through Physicochemical and Spectroscopic Measurement M Maharana, N Baruah, SK Nayak, N Meher, PK Iyer IEEE Transactions on Instrumentation and Measurement 68 (99), 1-11 , 2019 2019 Citations: 51
Evaluation of 134Ce/134La as a PET imaging theranostic pair for 225Ac α-radiotherapeutics KN Bobba, AP Bidkar, N Meher, C Fong, A Wadhwa, S Dhrona, A Sorlin, ... Journal of Nuclear Medicine 64 (7), 1076-1082 , 2023 2023 Citations: 49
Functional group engineering in naphthalimides: a conceptual insight to fine-tune the supramolecular self-assembly and condensed state luminescence N Meher, PK Iyer Nanoscale 11 (28), 13233-13242 , 2019 2019 Citations: 48
PSMA-targeted nanotheranostics for imaging and radiotherapy of prostate cancer N Meher, HF VanBrocklin, DM Wilson, RR Flavell Pharmaceuticals 16 (2), 315 , 2023 2023 Citations: 40
Development of CD46 targeted alpha theranostics in prostate cancer using 134Ce/225Ac-Macropa-PEG4-YS5 KN Bobba, AP Bidkar, A Wadhwa, N Meher, S Drona, AM Sorlin, ... Theranostics 14 (4), 1344 , 2024 2024 Citations: 33
Prostate-specific membrane antigen targeted deep tumor penetration of polymer nanocarriers N Meher, GW Ashley, AP Bidkar, S Dhrona, C Fong, SD Fontaine, ... ACS applied materials & interfaces 14 (45), 50569-50582 , 2022 2022 Citations: 28
Synthesis and preliminary biological assessment of carborane-loaded theranostic nanoparticles to target prostate-specific membrane antigen N Meher, K Seo, S Wang, AP Bidkar, M Fogarty, S Dhrona, X Huang, ... ACS applied materials & interfaces 13 (46), 54739-54752 , 2021 2021 Citations: 27
Modulation of amyloid aggregates into nontoxic coaggregates by hydroxyquinoline appended polyfluorene SR Chowdhury, M Agarwal, N Meher, B Muthuraj, PK Iyer ACS Applied Materials & Interfaces 8 (21), 13309-13319 , 2016 2016 Citations: 27
An Unprecedented Blueshifted Naphthalimide AIEEgen for Ultrasensitive Detection of 4‐Nitroaniline in Water via “Receptor‐Free” IFE Mechanism MN Khatun, AS Tanwar, N Meher, PK Iyer Chemistry–An Asian Journal 14 (24), 4725-4731 , 2019 2019 Citations: 24
Long alkyl chain induced OFET characteristic with low threshold voltage in an n-type perylene monoimide semiconductor MN Khatun, A Dey, N Meher, PK Iyer ACS Applied Electronic Materials 3 (8), 3575-3587 , 2021 2021 Citations: 23
Prostate-specific membrane antigen-targeted NIR phototheranostics for prostate cancer K Solanki, N Ahmed, N Srivastava, N Meher ACS Applied Bio Materials 7 (9), 5861-5884 , 2024 2024 Citations: 20
CD46-Targeted Theranostics for PET and 225 Ac-Radiopharmaceutical Therapy of Multiple Myeloma A Wadhwa, S Wang, B Patino-Escobar, AP Bidkar, KN Bobba, E Chan, ... Clinical Cancer Research 30 (5), 1009-1021 , 2024 2024 Citations: 20
