Stereotactic body radiation therapy (SBRT) has become a non-invasive alternative option for canine adrenal tumours with high surgical risks; however, its clinical benefits and risks are still to be fully understood. The goal of this multi-institutional retrospective study was to describe the clinical outcome and safety of SBRT for the treatment of 21 dogs with adrenal tumours. Ten were suspected pheochromocytomas, two adenocarcinomas, and the diagnosis was unknown in nine dogs. Vascular invasion was present in 81% of cases (17/21). Thirteen dogs received 3 fractions of 6 to 11 Gy, 7 received 5 fractions of 6 to 9 Gy, and 1 received 4 fractions of 6 Gy. For the 20 patients with follow-up imaging, 9 (43%) had partial response, 10 (47%) stable disease, and 1 (5%) progressive disease. Progression-free survival was 16.8 months (95% CI: 3.4-23), and overall survival time was 16.8 months (95% CI: 3.7-23.7). Twelve patients (57%) experienced acute adverse events (AEs); of those, seven were gastrointestinal grade ≥ III, including one grade V. Late AEs were suspected in seven dogs (33%), including gastrointestinal grade V in four of them. A total of five dogs (24%) died from radiation-related toxicities. Although SBRT seems to be effective against adrenal tumours, it was associated with a high morbidity and mortality rate, suggesting that re-evaluation of radiation therapy protocols is necessary for maintaining patient safety.

ABSTRACTStrontium‐90 plesiotherapy delivers high doses of radiation to superficial lesions (<3 mm depth) with excellent sparing of deeper tissues. The sealed‐source applicator tip is circular and 8–10 mm in diameter. Larger treatment fields are treated with multiple overlapping fields. The applicator cannot conform to angular extensions of irregularly shaped fields, resulting in unnecessary treatment of normal tissue, and overlapping fields can overdose in some areas. With strontium‐90 sources that have high activity and thus a high dose rate, small variations in duration and position of placement can be even more consequential. This prospective investigation used radiochromic film to evaluate the dosimetry of adjacent, static, overlapping fields compared with that of the same target area treated with the applicator in continuous motion intended to achieve the prescribed exposure to all points within the target. The intent was to minimize over‐ and underdosed areas. Three shapes of target field were used: single 2 cm circle, curvilinear field, and cloverleaf. Application times were calculated to deliver the dose to the surface, and the procedure was repeated by four operators for qualitative evaluation (1 Gy/100 cGy to target) and four operators to generate quantitative data (5 Gy/500 cGy to target). We found significant differences between methods among operators, dependent on the number of fields, and in dose drop‐off at the margin of the treated field. In almost every comparison, continuous motion was more homogenous (p ≤ .01 for standard deviation from expected dose). The continuous motion technique can be used for strontium plesiotherapy when the applicator must be held.

Purpose In the United States, breast cancer is the second leading cause of cancer-related death. Triple-negative breast cancer (TNBC) is of substantial concern, as it lacks the receptors usually targeted by conventional treatments. Triple-negative breast tumors have a high degree of copper metabolism for the synthesis of transporters, enzymes, and chaperones. Tetrathiomolybdate (TM) is a well-tolerated oral therapy that has been investigated for chelating copper from tumors in TNBC patients, resulting in extended remission. The overall goal of this research was to evaluate [64Cu]CuCl2 PET/CT imaging of copper utilization in this disease, in the presence and absence of TM. Procedures Uptake, internalization, and efflux studies were performed in TNBC cells versus normal cells. Biodistribution experiments were then conducted in TNBC xenograft-bearing mice that were administered TM versus controls. PET/CT imaging of mice carrying TNBC tumors was also performed in the presence and absence of TM. Finally, imaging was performed in a healthy cat and cats with mammary carcinoma. Results SUM149 TNBC cells selectively took up, internalized, and retained [64Cu]CuCl2 more avidly than normal fibroblasts. When SUM149-bearing mice were given TM, tumor uptake decreased and tracer accumulation shifted predominantly to the liver and kidneys, compared to control mice, in which large quantities of 64Cu were excreted into the intestines. These results were supported by PET/CT imaging of the mice. PET/CT of companion cats gave results similar to those obtained in mice, with high accumulation of radioactivity observed in the liver and gallbladder and moderate intestinal and renal clearance. In a cat with mammary carcinoma, [64Cu]CuCl2 was highly conspicuous, even in close proximity to the liver. Conclusions Utilization of [64Cu]CuCl2 in triple-negative breast cancer can be detected efficiently in cell and animal models of this disease. The tracer was also used successfully to evaluate TM therapy in the SUM149 TNBC mouse model. Furthermore, PET/CT imaging of both mice and cats with breast cancer shows the potential to monitor treatment with TM in a facile, noninvasive manner. We are currently conducting a clinical trial of [64Cu]CuCl2 PET/CT in companion cats with mammary carcinoma, with the future goal of evaluating the efficacy of TM in feline patients.

Advancements in molecular imaging and drug targeting have created a renaissance in the development of radiopharmaceuticals for therapy and theranostics. While some radiopharmaceuticals, such as Na[131I]I, have been used clinically for decades, new agents are being approved using small-molecules, peptides, and antibodies for targeting. As these agents are being developed, the need to understand dosimetry and biologic effects of the systemically delivered radiotherapy becomes more important, particularly as highly potent radiopharmaceuticals using targeted alpha therapy become clinically utilized. As the processes being targeted become more complex, and the radiobiology of different particulate radiation becomes more diverse, models that better recapitulate human cancer and geometry are necessary. Companion animals develop many of the same types of cancer, carrying many of the same genetic drivers as those seen in people, and the scale and geometry of tumours in dogs more closely mimics those in humans than murine tumour models. Key translational challenges in oncology, such as alterations in tumour microenvironment, hypoxia, heterogeneity, and geometry are addressed by companion animal models. This review paper will provide background on radiopharmaceutical targeting techniques, review the use of radiopharmaceuticals in companion animal oncology, and explore the translational value of treating these patients in terms of dosimetry, treatment outcomes, and normal tissue complication rates.

Thyroid follicular tumours may take up iodide via the sodium-iodide symporter. Knowledge of iodide uptake could then allow treatment with I-131 in dogs with high-risk tumours. The objective of this study was to determine the relationship between clinically detectable iodide uptake (as determined by scintigraphy and/or thyroxine concentrations) and sodium iodide symporter immunohistochemical labelling on histologically fixed thyroid tumours. Nineteen dogs were identified who were diagnosed with thyroid carcinoma and underwent surgery from November 2017 to July 2021. All had recorded thyroid hormone concentrations and were hyperthyroid and/or underwent preoperative nuclear imaging using planar scintigraphy (technetium-99m or I-123), or I-124 PET-CT. All dogs subsequently underwent surgery to remove the thyroid mass. Twenty-two tumours were submitted for histopathologic analysis immediately following surgery, which confirmed a diagnosis of thyroid carcinoma for each tumour. Images and/or thyroid hormone concentrations were reviewed for the included cases, and tumours were sorted into an avid/functional group (group 1) and a non-avid/functional group (group 2). The tumour tissues were re-examined histologically using sodium iodide symporter (NIS) immunohistochemistry (IHC). Group 1 contained 15 avid/functional tumours. Twelve of these tumours had membranous NIS IHC labelling. Group 2 contained 7 non-avid tumours. One of these tumours had membranous NIS IHC labelling. This resulted in an overall sensitivity and specificity for identification of avid/functional tumours with membranous NIS of 80.0% and 85.7%, respectively. NIS IHC may predict ion trapping in canine follicular thyroid tumours. Further studies using iodide-based imaging are warranted to better determine the clinical utility of this diagnostic modality.

Objective.To investigate different dosimetric aspects of90Y-IsoPet™ intratumoral therapy in canine soft tissue sarcomas, model the spatial spread of the gel post-injection, evaluate absorbed dose to clinical target volumes, and assess dose distributions and treatment efficacy.Approach.Six canine cases treated with90Y-IsoPet™ for soft tissue sarcoma at the Veterinary Health Center, University of Missouri are analyzed in this retrospective study. The dogs received intratumoral IsoPet™ injections, following a grid pattern to achieve a near-uniform dose distribution in the clinical target volume. Two dosimetry methods were performed retrospectively using the Monte Carlo toolkit OpenTOPAS: imaging-based dosimetry obtained from post-injection PET/CT scans, and stylized phantom-based dosimetry modeled from the planned injection points to the gross tumor volume. For the latter, a Gaussian parameter with variable sigma was introduced to reflect the spatial spread of IsoPet™. The two methods were compared using dose-volume histograms (DVHs) and dose homogeneity, allowing an approximation of the closest sigma for the spatial spread of the gel post-injection. In addition, we compared Monte Carlo-based dosimetry with voxel S-value (VSV)-based dosimetry to investigate the dosimetric differences.Main results.Imaging-based dosimetry showed differences between Monte Carlo and VSV calculations in tumor high-density areas with higher self-absorption. Stylized phantom-based dosimetry indicated a more homogeneous target dose with increasing sigma. The sigma approximation of the90Y-IsoPet™ post-injection gel spread resulted in a median sigma of approximately 0.44 mm across all cases to reproduce the dose heterogeneity observed in Monte Carlo calculations.Significance.The results indicate that dose modeling based on planned injection points can serve as a first-order approximation for the delivered dose in90Y-IsoPet™ therapy for canine soft tissue sarcomas. The dosimetry evaluation highlights the non-uniformity of absorbed doses despite the gel spread, emphasizing the importance of considering tumor dose heterogeneity in treatment evaluation. Our findings suggest that using Monte Carlo for dose calculation seems more suitable for this type of tumor where high-density areas might play an important role in dosimetry.

Companion dogs have served an important role in cancer immunotherapy research. Sharing similar environments and diets with humans, dogs naturally develop many of the same cancers. These shared exposures, coupled with dogs' diverse genetic makeup, make them ideal subjects for studying cancer therapies. Tumors like osteosarcoma, hemangiosarcoma, soft-tissue sarcoma, and non-Hodgkin lymphoma occur with greater frequency than their counterpart disease in humans. Canine brain tumors allow the study of therapy strategies with imaging, surgery, and radiotherapy equipment in veterinary patients with near-human geometry. Nonspecific immunostimulants, autologous and allogeneic vaccines, immune checkpoint inhibitors, and cellular therapies used in treating canine cancers have been tested in veterinary clinical trials. These treatments have not only improved outcomes for dogs but have also provided valuable insights for human cancer treatment. Advancements in radiation technology and the development of tools to characterize canine immune responses have further facilitated the ability to translate veterinary clinical trial results to human applications. Advancements in immunotherapy of canine tumors have directly supported translation to human clinical trials leading to approved therapies for patients with cancer around the world. The study of immunotherapy in dogs has been and will continue to be a promising avenue for advancing human cancer treatment.

Here we describe an anti-prostate-specific membrane antigen (PSMA) minibody (IAB2MA) conjugated to an octadentate, macrocyclic chelator based on four 1-hydroxypyridin-2-one coordinating units (Lumi804 [L804]) labeled with 89Zr (PET imaging) and 177Lu (radiopharmaceutical therapy), with the goal of developing safer and more efficacious treatment options for prostate cancer. Methods: L804 was compared with the current gold standard chelators, DOTA and deferoxamine (DFO), conjugated to IAB2MA for radiolabeling with 177Lu and 89Zr in cell binding, preclinical biodistribution, imaging, dosimetry, and efficacy studies in the PSMA-positive PC3-PIP tumor-bearing mouse model of prostate cancer. Results: Quantitative radiolabeling (>99% radiochemical yield) of L804-IAB2MA with 177Lu or 89Zr was achieved at ambient temperature in under 30 min, comparable to 89Zr labeling of DFO-IAB2MA. In contrast, DOTA-IAB2MA was radiolabeled with 177Lu for 30 min at 37°C in approximately 90% radiochemical yield, requiring further purification. Using europium(III) as a luminescent surrogate, high binding affinity of Eu-L804-IAB2MA to PSMA was demonstrated in PC3-PIP cells (dissociation constant, 4.6 ± 0.6 nM). All 4 radiolabeled constructs showed significantly higher levels of internalization after 30 min in the PC3-PIP cells than in PSMA-negative PC3-FLU cells. The accumulation of 177Lu- and 89Zr-L804-IAB2MA in PC3-PIP tumors and all organs examined (i.e., heart, liver, spleen, kidney, muscle, salivary glands, lacrimal glands, carcass, and bone) was significantly lower than that of 177Lu-DOTA-IAB2MA and 89Zr-DFO-IAB2MA at 96 and 72 h after injection, respectively. Generally, SPECT/CT and PET/CT imaging data showed no significant difference in the SUVmean of the tumors or muscle between the radiotracers. Dosimetry analysis via both organ-level and voxel-level dose calculation methods indicated significantly higher absorbed doses of 177Lu-DOTA-IAB2MA in tumors, kidney, liver, muscle, and spleen than of 177Lu-L804-IAB2MA. PC3-PIP tumor-bearing mice treated with single doses of 177Lu-L804-IAB2MA (18.4 or 22.2 MBq) exhibited significantly prolonged survival and reduced tumor volume compared with unlabeled minibody control. No significant difference in survival was observed between groups of mice treated with 177Lu-L804-IAB2MA or 177Lu-DOTA-IAB2MA (18.4 or 22.2 MBq). Treatment with 177Lu-L804-IAB2MA resulted in lower absorbed doses in tumors and less toxicity than that of 177Lu-DOTA-IAB2MA. Conclusion: 89Zr- and 177Lu-L804-IAB2MA may be a promising theranostic pair for imaging and therapy of prostate cancer.

OBJECTIVE To report local progression and survival in dogs following surgery and postoperative definitive radiotherapy (dRT) for management of soft tissue sarcoma (STS) and to evaluate risk factors for local progression and survival. METHODS Records were retrospectively reviewed at 9 referral hospitals for dogs managed with postoperative dRT between January 1, 2010, and January 1, 2020, following surgery for STS. Data related to presentation, surgery, dRT, systemic therapy, and outcome were abstracted. Selected variables were assessed for association with local progression and overall survival. RESULTS 272 dogs were included. Histologic grade was reported in 249 dogs: 102 were grade 1 (40.9%), 120 were grade 2 (48.2%), and 27 were grade 3 (10.8%). Local progression was suspected or confirmed in 56 dogs. Local progression rates were similar for grade 1 (24 of 89 [26.7%]), grade 2 (23 of 111 [20.7%]), and grade 3 tumors (6 of 22 [27.3%]). Previous recurrence (P = .010) and subsequent distant metastasis (P = .014) were associated with more frequent local progression; intensity-modulated radiotherapy was associated with decreased local progression (P = .025) compared to other forms of delivery. Age (P = .049), grade (P = .009), previous recurrence (P = .009), and institution type for surgery (P = .043) were associated with overall survival. CONCLUSIONS Outcomes for most dogs were good; however, the frequency of local progression indicates an ongoing need to critically appraise local management strategies, particularly for low-grade STS. Intensity-modulated radiotherapy was associated with lower rates of local progression and may be preferred to less precise forms of delivery. CLINICAL RELEVANCE These data may guide clinicians when making decisions regarding dRT for management of STS.

IntroductionZoledronic acid (ZOL) is a third-generation bisphosphonate with a higher affinity for bone resorption areas than earlier bisphosphonates (i.e., pamidronate, PAM). In human medicine, ZOL provides improved bone pain relief and prolonged time to skeletal-related events compared to its older generational counterparts. Preclinical studies have investigated its role as an anti-neoplastic agent, both independently and synergistically, with radiation therapy (RT). ZOL and RT act synergistically in several neoplastic human cell lines: prostate, breast, osteosarcoma, and fibrosarcoma. However, the exact mechanism of ZOL’s radiosensitization has not been fully elucidated.MethodsWe investigated ZOL’s ability to induce apoptosis in canine osteosarcoma cell lines treated with various doses of megavoltage external beam radiotherapy. Second, we evaluated cell cycle arrest in ZOL-treated cells to assess several neo-adjuvant time points. Finally, we treated 20 dogs with naturally occurring appendicular OS with 0.1 mg/kg ZOL IV 24 h before receiving 8 Gy of RT (once weekly fraction x 4 weeks).ResultsWe found that apoptosis was increased in all ZOL-treated cell lines compared to controls, and the combination of ZOL and RT resulted in dissimilar apoptosis between Abrams and D-17 and HMPOS cell lines. Cell cycle arrest (G2/M phase) was minimal and variable between cell lines but perhaps greatest at 48 h post-ZOL treatment. Only 10% of dogs treated with ZOL and RT developed pathologic fractures, compared to 44% of dogs historically treated with PAM and RT (p = 0.027).DiscussionZOL and RT appear to be a well-tolerated combination treatment scheme for non-surgical candidates; future studies must elucidate the ideal timing of ZOL.

153 Sm-DOTMP (CycloSam® ) is a newly-patented radiopharmaceutical for bone tumor treatment. DOTMP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonate) is a macrocyclic chelating agent with superior binding properties to 153 Sm when compared with EDTMP (Quadramet™, used for palliative treatment of bone cancer). CycloSam® was administered at 1 mCi/kg (37 MBq/kg) in a prospective pilot study to seven dogs with bone cancer resulting in no myelosuppression. Then, 13 dogs were enrolled in a prospective clinical trial study using traditional 3+3 dose escalation and starting at 1.5 mCi/kg. Baseline evaluation included hematologic and biochemical testing, diagnosis confirmation, thoracic and limb radiographs, technetium-99 m-HDP bone scintigraphy, and 18 F-FDG PET scan (SUVmax). Toxicity (primary endpoint) was assessed through weekly blood counts and adverse events. Dogs received 1.5 mCi/kg (n = 4), 1.75 mCi/kg (n = 6), and 2 mCi/kg (n = 3) of 153 Sm-DOTMP. Dose-limiting neutropenia and thrombocytopenia were seen at 2 mCi/kg. No dose-limiting nonhematologic toxicities occurred. Efficacy (secondary endpoint) was assessed by objective lameness measurement (body-mounted inertial sensors), owner quality-of-life (QoL) questionnaire, and repeat PET scan. Objective lameness measurement improved in four dogs (53%-60% decrease) was equivocal in three dogs, and worsened in four dogs (66%-115% increase); two dogs were not evaluable. Repeat 18 F-FDG PET scan results varied and change in lameness did not consistently correlate with SUVmax changes. QoL score worsened (n = 5) or was improved/stable (n = 7). Carboplatin chemotherapy (300 mg/m2 IV every 3 weeks ×4) started 4 weeks after 153 Sm-DOTMP injection. No dog died of chemotherapy-related complications. All dogs completed study monitoring. The recommended dose for CycloSam® in dogs is 1.75 mCi/kg, which resulted in some pain control with minimal toxicity and was safely combined with chemotherapy.

Abstract Background Radiation therapy (RT) is used for local pain alleviation in dogs with appendicular osteosarcoma (OS), especially among dogs that are poor surgical candidates for amputation. However, many historical reports of fractionated protocols lack time to fracture and fracture rates. Objectives The primary objectives of this retrospective study were to determine fracture rate and time to fracture of dogs receiving RT (coarse or fine fractionated) for appendicular OS. Secondary objectives were to evaluate tolerability and disease outcome measures. Methods Fifty‐one dogs that received RT as part of treatment for appendicular OS were available for evaluation. Forty‐five received coarse fractionation (C‐RT, 8 or 6 Gy per fraction protocols [C‐RT8 or C‐RT6]) while the remaining six received fine fractionation (F‐RT). Results The overall pathologic fracture rate was 37%. Pathologic fracture rate was significantly higher for dogs that received F‐RT (5/6, 83%) compared to dogs that received C‐RT (12/40, 30%, p = 0.021). In the 17 dogs that fractured, the overall median time to fracture was 57 days. For all dogs, the median progression free interval (PFI) and median overall survival time (OST) were 90 and 140 days, respectively. In a very small cohort of dogs (n = 7) treated with zoledronate and RT, fracture rate was 0% and extended survival times were noted. Conclusions In conclusion, C‐RT is recommended over F‐RT due to lower risk of pathologic fracture and similar PFI. Prospective evaluation of combined C‐RT and zoledronate, especially for dogs with poor surgical candidacy, is warranted for the treatment of canine appendicular osteosarcoma.

Radioactive iodine is frequently used for staging of human thyroid carcinomas. Iodine-124 scans performed using position emission tomography (PET) allow for more precise dosimetry of therapeutic radioiodine. The distribution of I-124 has not previously been described in veterinary medicine. The purpose of this prospective, exporatory, descriptive study is to evaluate the whole-body distribution of I-124 in dogs with suspected thyroid carcinoma. Ten dogs with either a cytologic diagnosis of a neuroendocrine neoplasm or biochemical hyperthyroidism were enrolled in a prospective clinical study. Whole-body I-124 PET/CT scans were performed and were evaluated for physiologic and pathologic uptake of I-124. The maximum and mean standardized uptake values (SUVmean) were recorded for several normal and abnormal tissues. Varying degrees of uptake were found in thyroid tumors (SUVmean = 66.37), ectopic thyroid masses (21.44), presumed metastatic lesions in lymph nodes (32.14), and the pulmonary parenchyma (4.50). In most dogs, physiologic uptake above background, measured in maximum SUV, was identified in parotid and mandibular salivary glands (14.00 and 1.57) the urinary tract (1.83), the gastrointestinal tract (19.90 stomach, 6.15 colon), the liver (1.41), and the heart (1.88). Occasionally, uptake was identified in the nasolacrimal duct (3.42), salivary duct (2.73), gallbladder (2.68), and anal gland (2.22). Physiologic uptake was also identified in normal thyroid glands and ectopic thyroid tissue. This study provides a baseline of pathologic and physiologic uptake of I-124 in dogs with thyroid carcinoma, to guide interpretation of future studies.

Abstract Purpose To perform precision dosimetry in yttrium-90 radioembolization through CT imaging of radiopaque microspheres in a rabbit liver model and to compare extracted dose metrics to those produced from conventional PET-based dosimetry. Materials and methods A CT calibration phantom was designed containing posts with nominal microsphere concentrations of 0.5 mg/mL, 5.0 mg/mL, and 25.0 mg/mL. The mean Hounsfield unit was extracted from the post volumes to generate a calibration curve to relate Hounsfield units to microsphere concentration. A nominal bolus of 40 mg of microspheres was administered to the livers of eight rabbits, followed by PET/CT imaging. A CT-based activity distribution was calculated through the application of the calibration curve to the CT liver volume. Post-treatment dosimetry was performed through the convolution of yttrium-90 dose-voxel kernels and the PET- and CT-based cumulated activity distributions. The mean dose to the liver in PET- and CT-based dose distributions was compared through linear regression, ANOVA, and Bland–Altman analysis. Results A linear least-squares fit to the average Hounsfield unit and microsphere concentration data from the calibration phantom confirmed a strong correlation (r 2 > 0.999) with a slope of 14.13 HU/mg/mL. A poor correlation was found between the mean dose derived from CT and PET (r 2 = 0.374), while the ANOVA analysis revealed statistically significant differences (p < 10−12) between the MIRD-derived mean dose and the PET- and CT-derived mean dose. Bland–Altman analysis predicted an offset of 15.0 Gy between the mean dose in CT and PET. The dose within the liver was shown to be more heterogeneous in CT than in PET with an average coefficient of variation equal to 1.99 and 1.02, respectively. Conclusion The benefits of a CT-based approach to post-treatment dosimetry in yttrium-90 radioembolization include improved visualization of the dose distribution, reduced partial volume effects, a better representation of dose heterogeneity, and the mitigation of respiratory motion effects. Post-treatment CT imaging of radiopaque microspheres in yttrium-90 radioembolization provides the means to perform precision dosimetry and extract accurate dose metrics used to refine the understanding of the dose–response relationship, which could ultimately improve future patient outcomes.

The last decade has witnessed the creation of a highly effective approach to in vivo pretargeting based on the inverse electron demand Diels-Alder (IEDDA) click ligation between tetrazine (Tz) and trans-cyclooctene (TCO). Despite the steady progression of this technology toward the clinic, concerns have persisted regarding whether this in vivo chemistry will work in humans given their larger size and blood volume. In this work, we describe the use of a 64Cu-labeled Tz radioligand ([64Cu]Cu-SarAr-Tz) and a TCO-bearing bisphosphonate (TCO-BP) for the pretargeted positron emission tomography (PET) imaging of osteodestructive lesions in a large animal model: companion dogs. First, in a small animal pilot study, healthy mice were injected with TCO-BP followed after 1 or 6 h by [64Cu]Cu-SarAr-Tz. PET images were collected 1, 6, and 24 h after the administration of [64Cu]Cu-SarAr-Tz, revealing that this approach produced high activity concentrations in the bone (>20 and >15%ID/g in the femur and humerus, respectively, at 24 h post injection) as well as high target-to-background contrast. Subsequently, companion dogs (n = 5) presenting with osteodestructive lesions were administered TCO-BP (5 or 10 mg/kg) followed 1 h later by [64Cu]Cu-SarAr-Tz (2.2-7.3 mCi; 81.4-270.1 MBq). PET scans were collected for each dog 4 h after the administration of the radioligand, and SUV values for the osteodestructive lesions, healthy bones, and kidneys were determined. In these animals, pretargeted PET clearly delineated healthy bone and produced very high activity concentrations in osteodestructive lesions. Low levels of uptake were observed in all healthy organs except for the kidneys and bladder due to the renal excretion of excess radioligand. Ultimately, this work not only illustrates that pretargeted PET with TCO-BP and [64Cu]Cu-SarAr-Tz is an effective tool for the visualization of osteodestructive lesions but also demonstrates for the first time that in vivo pretargeting based on IEDDA click chemistry is feasible in large animals.

Hypoxia is associated with neoplastic tissue, protecting cancer cells from death by irradiation and chemotherapy. Identification of hypoxic volume of tumors could optimize patient selection for hypoxia-directed medical, immunological, and radiation therapies. Clostridium novyi-NT (CNV-NT) is an oncolytic bacterium derived from attenuated wild-type Clostridium novyi spores, which germinates exclusively in the anaerobic core of tumors with low-oxygen content. The hypothesis was that 64Cu-ATSM would localize to regions of hypoxia, and that greater hypoxic volume would result in greater germination of Clostridium novyi-NT (CNV-NT). Tumor-bearing companion dogs were recruited to a veterinary clinical trial. Dogs received a CT scan, 18F-FDG PET scan (74 MBq) and 64Cu-ATSM PET scan (74 MBq). Scan regions of interest were defined as the highest 20% of counts/voxel for each PET scan, and regions with voxels overlapping between the two scans. Maximum standardized uptake value (MaxSUV) and threshold volume were calculated. Direct oximetry was performed in select tumors. Tumor types evaluated included nerve sheath tumor (10), apocrine carcinoma (1), melanoma (3) and oral sarcoma (6). MaxSUVATSM ranged from 0.3-6.6. Measured oxygen tension ranged from 0.05-89.9 mmHg. Inverse of MaxSUVATSM had a linear relationship with oxygen tension (R2 = 0.53, P = 0.0048). Hypoxia <8 mmHg was associated with an SUVATSM > 1.0. Hypoxic volume ranged from 0 to 100% of gross tumor volume (GTV) and MaxSUVATSM was positively correlated with hypoxic volume (R = 0.674; P = 0.0001), but not GTV (P = 0.182). Tumor hypoxic volume was heterogeneous in location and distribution. 64Cu-ATSM-avid regions were associated with differential CT attenuation. Hypoxic volume did not predict CNV-NT germination. 64Cu-ATSM PET scanning predicts hypoxia patterns within spontaneously occurring tumors of dogs as measured by direct oxymetry. Total tumor volume does not accurately predict degree or proportion of tumor hypoxia.

ObjectivesTo further characterise solitary osseous plasmacytoma in dogs, an extremely rare disease. To describe diagnosis, disease progression and treatment outcomes in dogs with solitary osseous plasmacytoma.Materials and MethodsRetrospective review of dogs with solitary osseous plasmacytomas that were diagnosed and treated at a single institution from 2005 to 2019. Kaplan–Meier single group survival analysis was used to estimate median survival time and progression‐free interval.ResultsThirteen dogs met the inclusion criteria for the study, and of those, 11 were treated. The median age at diagnosis was 8 years (range 4 to 11). Most solitary osseous plasmacytomas occurred in the vertebrae (n=8). Other sites included the maxilla (n=2), the mandible (n=1), the tibia (n=1) and the carpus (n=1). The median survival time for all dogs with solitary osseous plasmacytoma was 912 days (range 5 to 2179), and the progression‐free interval for treated dogs was 310 days (range 22 to 2179). Most dogs were treated with radiation therapy (n=10) with nine of 10 receiving a definitive, daily fractionated protocol and with five of ten having had neoadjuvant surgery. Seven dogs received chemotherapy, which was initiated after progressive disease in five dogs. The median survival time for dogs that completed radiation therapy (n=9) was 1166 days (range 545 to 2179). While five dogs developed lesions at other sites, no dogs progressed to multiple myeloma.Clinical SignificanceCanine solitary osseous plasmacytomas can be managed long term with appropriate local therapy. This observation reflects the biologic behaviour observed in humans.

A 6-year-old dog presented with a modified Adams stage 3 angiofibroma of the right nasal cavity, causing fluid accumulation along the right frontal sinus. Treatment consisted of step-and-shoot intensity-modulated radiation therapy in 12 daily treatments of 3.5 Gy, for a total dose of 42 Gy to 95% of the planning target volume. The dog developed self-limiting grade 2 oral mucositis which resolved within 2 weeks of course completion. A recheck exam 668 days after treatment confirmed a stable disease response by RECIST and a tumor volume decrease of 55.4%.