About

Jonathan W. Engle, PhD, is an Associate Professor in the Departments of Medical Physics and Radiology at the University of Wisconsin. He specializes in radionuclide production, accelerator targetry, and radiochemistry, functioning as an analytical and preparative radiochemist in clinical and pre-clinical positron emission tomography (PET) scanning environments. Dr. Engle is involved in constructing automated radiochemistry modules for routine and novel syntheses and in advancing PET radiotracer production facilities from basic setups to routine production and research activities. He leads the Cyclotron Research Group, focusing on radiometals production and innovative small accelerator targetry, particularly for producing positron and Auger electron emitting radionuclides such as Zr-89, Cu-64, As-72, Y-86, Br-77, Ga-68, Co-55, and Sc-44. His research efforts include the development of new methods for radionuclide production, contributing significantly to the field of radiochemistry and medical imaging.

Research topics

• Internal medicine
• Medicine
• Pathology
• Cancer research
• Chemistry
• Nanotechnology
• Materials science
• Pharmacology
• Biochemistry
• Biology
• Immunology
• Neuroscience
• Oncology
• Metallurgy
• Psychology

Selected publications

• <p>Small Cyclotron Production of Non-Carrier-Added 103Pd from Electroplated Rh Targets</p>

  SSRN Electronic Journal · 2026-01-01

  preprintOpen accessSenior author
  PublisherDOI

• Improved X-ray absorption capability of Core-shell nano-transducer in situ enhances γ-ray-excited radioluminescence imaging in vivo

  Journal of Nanobiotechnology · 2026-01-13

  articleOpen access

  Radioluminescence imaging (RLI) using nanoscintillators offers great potential for biomedical applications, yet remains constrained by low quantum efficiency and the reliance of Cerenkov imaging on high-energy radionuclides. The rational design of core-shell nano-transducers overcomes these constraints by enhancing X-ray absorption and energy confinement, thereby enabling efficient γ-ray excited radioluminescence. We engineered NaGdF₄:15%Eu@NaLuF₄ core-shell nanoparticles as a superior nano-scintillator, designed to leverage Technetium-99m (99mTc) as an ideal excitation source. The key advantage of our system lies in its ability to efficiently convert the low-energy electron emissions from 99mTc into intense radioluminescence, completely bypassing the Cerenkov threshold and thus overcoming the key limitations of Cerenkov radiation. The optimized core-shell structure exhibited a radioluminescence intensity slope (k1) of 10.9 × 104 (p/s/cm2/sr)/MBq under 99mTc excitation, representing a 110% enhancement over the core-only nanoparticles. This enhanced scintillation output was paired with a remarkable CT contrast slope (k₂) of 47.6 HU/(mg/mL), demonstrating superior X-ray absorption capability. Capitalizing on these attributes, when integrated with 99mTc-sulfur colloid, this platform enabled background-free, multimodal SPECT/CT/RLI for high-contrast sentinel lymph node mapping and precise image-guided resection in murine models, the success of which was conclusively confirmed by histology. This work presents a progressive optimization of lanthanide-based nanoparticles (LnNPs) scintillators, unveiling their structure-dependent radioluminescence properties for enhanced output efficiency. It thereby provides key insights into energy transfer processes within core-shell architectures and fundamentally expands the repertoire of applicable radionuclides for optical imaging.

  PublisherDOI

• Radiolabeling Diaminosarcophagine with Cyclotron-Produced Cobalt-55 and [55Co]Co-NT-Sarcage as a Proof of Concept in a Murine Xenograft Model

  UNC Libraries · 2026-04-21

  articleOpen access

  Cobalt-sarcophagine complexes exhibit high kinetic inertness under various stringent conditions, but there is limited literature on radiolabeling and in vivo positron emission tomography (PET) imaging using no carrier added ⁵⁵Co. To fill this gap, this study first investigates the radiolabeling of DiAmSar (DSar) with ⁵⁵Co, followed by stability evaluation in human serum and EDTA, pharmacokinetics in mice, and a direct comparison with [⁵⁵Co]CoCl₂ to assess differences in pharmacokinetics. Furthermore, the radiolabeling process was successfully used to generate the NTSR1-targeted PET agent [⁵⁵Co]Co-NT-Sarcage (a DSar-functionalized SR142948 derivative) and administered to HT29 tumor xenografted mice. The [⁵⁵Co]Co-DSar complex can be formed at 37 °C with purity and stability suitable for preclinical in vivo radiopharmaceutical applications, and [⁵⁵Co]Co-NT-Sarcage demonstrated prominent tumor uptake with a low background signal. In a direct comparison with [⁶⁴Cu]Cu-NT-Sarcage, [⁵⁵Co]Co-NT-Sarcage achieved a higher tumor-to-liver ratio but with overall similar biodistribution profile. These results demonstrate that Sar would be a promising chelator for constructing Co-based radiopharmaceuticals including ⁵⁵Co for PET and ^58mCo for therapeutic applications.

  PublisherDOI

• 21P 52gMn-DOTA immunoPET of FAP-targeting antibodies

  ESMO Open · 2026-04-01

  articleOpen accessSenior author

  Background: Fibroblast activation protein-a (FAP) is a serine protease overexpressed by cancer-associated fibroblasts and linked to poor clinical outcomes.FAP-targeted radiopharmaceuticals enable imaging of metastatic castration-resistant prostate cancer.While 89 Zr-DFO (t 1/2 = 3.27 d) is widely used for immunoPET, many therapeutic agents will rely on DOTA to complex heavier metals with varying coordination chemistries.52g Mn (t 1/2 =5.6 d) offers a half-life suitable for antibodies with long circulation times and potential theranostic pairing.This proof-of-concept study evaluates 52g Mn-DOTA labeling of a fully humanized IgG (huB12), as well as a camelid derived VHH fused to a human IgG scaffold, F7-fc, via DOTA linker, for extended immunoPET imaging.Methods: 52g Mn-DOTA-huB12 or 52g Mn-DOTA-F7fc was injected intravenously in athymic nude mice bearing CWR-R1-EnzR FAP + xenografts.PET/CT imaging was performed daily for up to 13 days using an Inveon system.Tumor uptake was quantified using ROI analysis.Ex vivo biodistribution was assessed by gamma counting and expressed as percent injected activity per gram (% IA/g), with decay correction to injection time.Results: 52g Mn-DOTA-huB12 demonstrated high and sustained tumor uptake, peaking at 9.97 2.2 %IA/g at 6 days post-injection and remaining at 8.68 1.8 % IA/g at day 13.Ex vivo tumor uptake (8.57 0.02 % IA/g) corroborated imaging results.52g Mn-DOTA-F7-Fc showed lower uptake, peaking at 7.85 4.0 %IA/g at 2 days post injection, with ex vivouptake of 8.74 0.04 %IA/g.Minimal bone and muscle uptake for both tracers indicates in vivo stability of the 52g Mn-DOTA complex. Conclusions:Comparative evaluation with 89 Zr-DFO-labeled analogs highlights 52g Mn-DOTA as a stable alternative radiometal for immunoPET, avoiding the in vivo dissociation and off-target bone uptake associated with 89 Zr -DFO complexes.The favorable half-life and DOTA compatibility of 52g Mn make it well suited for imaging antibodies and engineered multi-domain or biparatopic targeting vectors with long circulation times.These results support broader translation of 52g Mn -labeled antibodies beyond FAP, particularly for next-generation theranostic constructs requiring long-lived, macrocycle-chelated PET tracers.

  PublisherOA PDFDOI

• A MET-Targeted Variable New Antigen Receptor (VNAR) Theranostic for Non-Small Cell Lung Cancer

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-02

  articleOpen access

  Abstract The MET receptor tyrosine kinase is mutated or amplified in ∼6% of non-small cell lung cancer (NSCLC) and overexpressed in ∼80% of all NSCLC cases. A theranostic agent that can both see and treat MET-altered NSCLC has never been described before in the literature. Here, we report a shark-derived single-domain variable new antigen receptor (VNAR) for MET with theranostic applications. Following the immunization of a juvenile nurse shark ( Ginglymostoma cirratum ) with the extracellular domain of human MET, we identified a VNAR clone that specifically engaged MET with high affinity. Engineering the lead VNAR into a bivalent human Fc, vMET1-Fc, yielded a construct that selectively targeted and was internalized by MET-positive cells without affecting cell viability or downstream MET signaling. When radiolabeled with the positron emitting isotope Zr-89, [ 89 Zr]Zr-vMET1-Fc enabled longitudinal PET/CT imaging. High tumor uptake with low background was observed in MET-positive NSCLC xenografts administered [ 89 Zr]Zr-vMET1-Fc. As a targeted beta-particle radiotherapy, [¹⁷⁷Lu]Lu-vMET1-Fc resulted in marked tumor-growth delay and exhibited a favorable toxicity profile, collectively improving progression-free survival in NSCLC mouse models. Non-human primate PET/CT imaging studies with ([⁸⁹Zr]Zr-vMET1-Fc in healthy rhesus macaques confirmed favorable biodistribution and dosimetry, predictable clearance, and minimal off-target uptake. Additional blood chemistry analysis found no significant immune response or cytotoxicity. Together, these findings establish vMET1-Fc as a theranostic agent for imaging and treating MET-altered NSCLC. Statement of Significance A shark-derived antibody selectively targeting MET shows preclinical efficacy as a theranostic agent for MET-altered cancer.

  PublisherOA PDFDOI

• Prenatal Stress and Prenatal Alcohol Alter the Adult Dopamine System and Alcohol Consumption: Dopamine Drives Drinking Behavior in a Prospective 20-Year Longitudinal Experiment with Rhesus Macaques

  Journal of Neuroscience · 2026-02-02

  articleOpen access

  Given the prevalence of alcohol use and stress during pregnancy, we examined the effects in offspring of prenatal alcohol and stress on the dopamine system and drinking behavior in a primate model. In a 20-year prospective longitudinal experiment, we studied alcohol-naive adult rhesus monkeys of both sexes bred from mothers randomly assigned during pregnancy to consume moderate alcohol, be exposed to mild stress, both, or neither. Positron emission tomography (PET) was used to measure dopamine D 2 -type receptor (D2) and transporter (DAT) availability in substantia nigra/ventral tegmental area (SN/VTA), striatum, and prefrontal cortex (PFC), at baseline and after chronic fixed-dose drinking in offspring. After the follow-up PET scans, monkeys were given ad libitum access to alcohol. Findings were: (1) prenatal stress increased DAT in SN/VTA and striatum, while an interaction of prenatal stress and alcohol altered D2 in PFC; (2) prenatal alcohol alone increased the fixed-dose drinking rate; (3) in the three brain regions, low baseline D2 predicted faster fixed-dose drinking rate, and changes in DAT from baseline to follow-up predicted consumption in subsequent ad libitum drinking; and (4) no significant alteration of D2 or DAT due to drinking was observed. This experiment highlights the sensitivity of the primate dopamine system to prenatal perturbations, dopamine's role in drinking, and an individual neuroadaptive response to chronic alcohol consumption. The results suggest that alcohol abuse may originate, in part, from prenatal alcohol exposure. Moreover, reports in AUD of lower D2 might reflect preexisting dopamine receptor status rather than resulting entirely from alcohol consumption.

  PublisherOA PDFDOI

• Tuning the Structural Properties of a Single-Domain Antibody Scaffold for Improved Fibroblast Activation Protein Targeting

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-13

  articleOpen access

  ABSTRACT Fibroblast activation protein (FAP) is an attractive target for the development of cancer theranostics due to its selective expression on cancer-associated fibroblasts (CAFs). While a number of small-molecule FAP inhibitors (FAPIs) have been developed, few biologics have been investigated as FAP targeting vectors. Camelid-derived single-domain antibodies, or variable-heavy-heavy domains (VHHs), offer a compelling alternative, combining high affinity with versatile engineering options. In this study, we first identified a novel anti-FAP VHH, F7, from an affinity-matured camelid phage display library. To investigate how valency and molecular weight affected target engagement and in vivo properties, F7 was engineered into three formats: a monomer (F7), a tethered dimer (F7D), and an Fc-fusion protein (F7-Fc). All three were specific for FAP with the two bivalent constructs demonstrating picomolar affinity. Positron emission tomography imaging in FAP-positive xenograft models revealed distinct pharmacokinetic profiles across constructs with notable differences in tumor uptake and clearance. F7 had rapid uptake and clearance resulting in significantly higher tumor uptake than FAPI-46. Low molecular weight bivalent F7D demonstrated similar kinetics but was retained by the tumor resulting in a high tumor-to-blood ratio with secondary uptake limited to clearance organs. The largest construct, F7-Fc, resulted in the highest tumor uptake and allowed for longitudinal imaging. Absorbed dose calculations confirmed that tumors received significantly higher radiation doses compared to normal tissues. These findings demonstrate that tuning VHH scaffold size and valency can improve biodistribution and retention, establishing F7-based constructs as promising targeting vectors for FAP.

  PublisherOA PDFDOI

• Cyclotron-Produced [51Mn]MnCl2 PET/MR Detects Surgically Induced Neuropathic Pain in Rats

  Nuclear Medicine and Biology · 2025-11-01

  articleOpen accessSenior author
  PublisherDOI

• Radionuclide-Dependent Stimulation of Antitumor Immunity in GD2-Targeted Radiopharmaceutical Therapy Combined with Immune Checkpoint Inhibitors

  Radiation · 2025-12-09

  articleOpen access

  Radiopharmaceutical therapy (RPT) offers tumor-selective radiation delivery and represents a promising platform for combination with immune checkpoint inhibitors (ICIs). While prior studies suggest that RPT can stimulate antitumor immunity, synergy with ICIs may depend on radionuclide properties, absorbed dose, and radiation distribution within the tumor microenvironment. This study evaluated how radionuclide selection and dose influence immune stimulation and therapeutic efficacy of GD2-targeted antibody-based RPT combined with ICIs. Dinutuximab, an anti-GD2 monoclonal antibody, was radiolabeled with β−-emitters (90Y, 177Lu) or an α-emitter (225Ac). C57Bl6 mice bearing GD2+ tumors received 4 or 15 Gy tumor-absorbed doses, determined by individualized dosimetry, with or without dual ICIs (anti-CTLA-4 and anti-PD-L1). In vivo imaging, ex vivo biodistribution, survival, histological, and gene expression analyses were performed to assess therapeutic and immunological outcomes. All radiolabeled constructs demonstrated preferential uptake in GD2+ tumors. Combination therapy improved survival in a radionuclide- and dose-dependent manner, with the greatest benefit in the 225Ac + ICI group at 15 Gy. Treatment activated type I interferon signaling and increased MHC-I and PD-L1 expression. Notably, 90Y reduced regulatory T cells, enhancing CD8+/Treg ratios, while 225Ac induced robust interferon-driven activation. Radionuclide selection and absorbed dose critically shape immune and therapeutic outcomes of antibody-based RPT combined with ICIs, underscoring the importance of delivery mechanism and dose optimization in combination therapy strategies.

  PublisherOA PDFDOI

• Preclinical Studies for Novel Theranostic Radiopharmaceutical 3-[76Br/77Br]bromo-pHPG

  Nuclear Medicine and Biology · 2025-11-01

  article
  PublisherDOI

Recent grants

• Combining targeted radionuclide therapy with a localized in situ vaccine to overcome immune suppression in the tumor microenvironment and augment T cell responses

  NIH · $25.0M · 2020–2026

Frequent coauthors

• Weibo Cai

  200 shared

• Todd E. Barnhart

  University of Wisconsin–Madison

  199 shared

• Eduardo Aluicio‐Sarduy

  University of Wisconsin–Madison

  116 shared

• Dawei Jiang

  114 shared

• Reinier Hernandez

  University of Wisconsin–Madison

  56 shared

• Kendall E. Barrett

  University of Wisconsin–Madison

  46 shared

• F.M. Nortier

  Los Alamos National Laboratory

  44 shared

• Peng Huang

  Sichuan Cancer Hospital

  42 shared

Education

• Ph.D., Radiology

  University of Wisconsin–Madison

  2000

• M.S., Radiology

  University of Wisconsin–Madison

  1996

• B.S., Radiology

  University of Wisconsin–Madison

  1994

Awards & honors

• Department of Energy Early Career Award (2016)