Jimmy C. Lattimer

Comparison of Systemic Toxicities of 177Lu-DOTMP and 153Sm-EDTMP Administered Intravenously at Equivalent Skeletal Doses to Normal Dogs

Bone-seeking radiopharmaceuticals have been used to effectively treat cancer arising from and metastasizing to bone in humans and dogs. The rate of complete tumor control is low, and the geographic distribution of available compounds is limited by their half-lives. This experiment was done to evaluate in normal dogs the toxicity of 177Lu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonate (177Lu-DOTMP) used as a potential therapeutic radiopharmaceutical. Methods: Four normal purpose-bred dogs were administered 177Lu-DOTMP at a dose of 8.14 MBq/kg and monitored for 84 d for evidence of toxicity in the bone marrow and vital organs. Results: No statistically significant alterations in the biochemical profile, white blood cell count, or platelet count were observed in any dog. Very mild decreases in the red cell count were seen on day 84. No microscopic evidence of toxicity was present at necropsy. Conclusion: The dogs receiving 177Lu-DOTMP tolerated the administration and the effects of the compound without apparent clinical toxicity. The results of this experiment support the further evaluation in tumor-bearing dogs of 177Lu-DOTMP as a potential therapy for metastatic bone cancer and primary bone tumors in humans and dogs.

Gum arabic-coated radioactive gold nanoparticles cause no short-term local or systemic toxicity in the clinically relevant canine model of prostate cancer

Introduction Gum arabic-coated radioactive gold nanoparticles (GA-198AuNPs) offer several advantages over traditional brachytherapy in the treatment of prostate cancer, including homogenous dose distribution and higher dose-rate irradiation. Our objective was to determine the short-term safety profile of GA-198AuNPs injected intralesionally. We proposed that a single treatment of GA-198AuNPs would be safe with minimal-to-no evidence of systemic or local toxicity. Methods Nine dogs with spontaneously occurring prostatic cancer were treated. Injections were performed with ultrasound or computerized tomography guidance. Complete blood counts, chemistry panels, and urinalyses were performed at weekly intervals for 1 month and imaging was repeated 4 weeks postinjection. Planar scintigraphic images were obtained within 30 minutes of injection. Results No statistically significant difference was found in any hematologic or biochemical parameter studied, nor was any evidence of tumor swelling or abscessation found in eight dogs with repeat imaging; one dog died secondary to urethral obstruction 12 days following injection. At 30 minutes postinjection, an average of 53% of injected dose in seven dogs was retained in the prostate, with loss of remaining activity in the bladder and urethra; no systemic uptake was detected. Conclusion GA-198AuNP therapy had no short-term toxicity in the treatment of prostatic cancer. While therapeutic agent was found in the prostate immediately following injection, some loss of agent was detected in the bladder and urethra. Localization of radioactivity within the prostate was lower than anticipated and likely due to normal vestigial prostatic ducts. Therefore, further study of retention, dosimetry, long-term toxicity, and efficacy of this treatment is warranted prior to Phase I trials in men.

Kartagener’s Syndrome in a Dachshund Dog

Kartageners syndrome (KS) is a rare, congenital condition characterized by situs inversus, rhinosinusitis, and bronchiectasis. An underlying ciliary dysfunction (e.g., immotility or dyskinetic beating) produces most of the clinical signs seen in affected animals. This case report reviews the history, clinical signs, and diagnosis of KS in a male, long-haired dachshund. This is the first known report of KS, and thus primary ciliary dyskinesia, in this breed of dog.

RADIATION AND CISPLATIN FOR TREATMENT OF CANINE URINARY BLADDER CARCINOMA

Two cases of canine urinary bladder carcinoma were treated with combined radiation and cisplatin. Total radiation dose was 4400 cGy for one dog and 4800 cCy for the other. Cobalt 60 radiation was fractioned using 400 cGy per fraction. Cisplatin was administered intraarterially at a dose of 50 mg/m2 divided equally six to seven hours before the first three radiation fractions. Cisplatin was administered before the last three radiation fractions at the same dose and time, but was infused intravenously. Objective evaluation using double contrast cystograms revealed reduction in tumor size in both dogs. The therapy was well-tolerated with minimal side effects.

Evaluation of a B-cell leukemia-lymphoma 2-specific radiolabeled peptide nucleic acid–peptide conjugate for scintigraphic detection of neoplastic lymphocytes in dogs with B-cell lymphoma

OBJECTIVE To evaluate use of a radiolabeled peptide nucleic acid-peptide conjugate (RaPP) targeting B-cell leukemia-lymphoma 2 (BCL2) mRNA for scintigraphic detection of neoplastic lymphocytes in dogs with B-cell lymphoma and to assess associations among RaPP uptake, time to tumor progression (TTP), and BCL2 mRNA expression. ANIMALS 11 dogs with B-cell lymphoma and 1 clinically normal dog. PROCEDURES Scintigraphic images were acquired 1 hour after IV injection of the RaPP. Regions of interest (ROIs) were drawn around lymph nodes, liver, and spleen; ROI intensity (relative to that of an equally sized region of muscle in the same image) was measured. Each ROI was also subjectively categorized as positive or negative for increased RaPP uptake. Expression of BCL2 mRNA was determined via quantitative reverse transcriptase PCR assay of a lymph node sample from dogs with lymphoma. Associations among imaging results, TTP, and BCL2 mRNA expression were evaluated. RESULTS Increased RaPP uptake was detected in affected tissues of dogs with lymphoma. Dogs with superficial cervical lymph node ROIs categorized as negative (n = 8) for increased RaPP uptake had a significantly longer TTP than did dogs for which this ROI was considered positive (2). Measured intensity of mandibular and superficial cervical lymph node ROIs was negatively associated with TTP. Associations among BCL2 mRNA and ROI intensity or TTP were not significant. CONCLUSIONS AND CLINICAL RELEVANCE Increased RaPP uptake at mandibular or superficial cervical lymph node ROIs may be a negative prognostic indicator in dogs with lymphoma. A larger investigation is needed to determine clinical value of the RaPP for disease detection and prognostication.

REIRRADIATION OF RECURRENT CANINE NASAL TUMORS

Canine nasal tumors are typically treated with radiation therapy but most patients develop local recurrence. Our purpose was to evaluate tumor and normal tissue response to reirradiation in nine dogs. The median dose delivered with the first protocol was 50 Gy (range 44-55 Gy) and the median fraction number was 18 (range 15-20). For the second protocol, the median dose was lower intentionally, median of 36 Gy (range 23-44 Gy), without changing the median fraction number of 18 (range 14-20) to avoid late effects. The median time between protocols was 539 days (range 258-1652 days). Median survival was 927 days (95% confidence interval [CI] 423-1767 days). Median time to progression following the first and second courses was 513 days (95% CI 234-1180 days) and 282 days (95% CI 130-453 days), respectively. These were not significantly different (P=0.086). The qualitative response assessment was better for the first course compared with the second (P=0.018). Severity and timing of skin, mucous membrane, and ocular effects were similar for early side effects between the two courses (P>0.05 for all comparisons). All dogs experienced some late side effects, with two out of nine being classified as severe. These severe effects were blindness in each dog, possibly related to tumor recurrence. Reirradiation of canine nasal tumors resulted in a second clinical remission in eight of nine dogs, although the second response was less complete. Acute and late effects for seven of nine patients were not life threatening, indicating that reirradiation of canine nasal tumors may be a viable treatment option after recurrence.

Retrospective study of cecocolic intussusception (cecal inversion) in nine horses (1982–1998)

Summary We retrospectively evaluated the medical records and obtained follow-up information for nine horses which had been treated for cecocolic intussusception (CCI) between January 1982 and April 1998. During the 16-year study period, CCI was diagnosed in nine of 748 horses in which exploratory celiotomy was undertaken for abdominal pain, representing an incidence of 1.2%. Most affected horses (78%) were less than four years of age (median age was 12 months, age range was five months to 15 years). Cecocolic intussusception affected male horses (78%) more commonly than female horses. The most common clinical presentation was abdominal pain of a severe, acute nature or milder but recurrent signs of abdominal pain persisting in spite of conservative treatment for several days. Correction of CCI by either simple reduction or reduction followed by partial typhlectomy was successful if compromise of the intestine by devitalization and adhesion formation was not found at surgery. Definitive diagnosis of CCI necessitates exploratory celiotomy, although an ultrasonographic examination of the abdomen may confirm the diagnosis in some cases. When recognized early during the course of disease, surgical correction of CCI is associated with a favorable outcome; of the eight horses which underwent surgery in our series, five horses (63%) survived surgical correction of CCI. Handling of compromised gut during reduction of CCI necessitates extreme caution because the risk of intestinal tearing is quite high.

Treatment of a malignant pheochromocytoma in a dog using 131I metaiodobenzylguanidine.

A 12 yr old castrated male Yorkshire terrier was presented with a history of an inoperable pheochromocytoma. Physical examination revealed a large, midabdominal mass. Neurologic examination was normal at presentation. An abdominal computed tomography scan revealed a 215 cm(3) mass in the region of the right kidney. Forty-eight hours after IV injection of 370 megabecquerels (MBq, equivalent to10 millicuries [mCi]) of metaiodobenzylguanidine labeled with radioactive iodine ([(131)I]MIBG), standard planar scintigraphy was performed. A diffuse area of moderate uptake was noted in the midabdominal region. The dog experienced stable disease for 1.5 mo after injection based on a follow-up computed tomography (CT) scan; however, 5 mo after injection, repeat CT imaging revealed progression of the tumor, and a second IV injection of 370 MBq (10 mCi) of [(131)I]MIBG was administered. The dog died 3 wk after the second injection as a result of gastrointestinal blood loss that was believed to be caused by compression-induced bowel ischemia by the mass. A full necropsy was not performed, but the mass was removed for histologic evaluation, which confirmed the diagnosis of pheochromocytoma. This report is the first to document the treatment of canine pheochromocytoma using [(131)I]MIBG.

THE ELECTRON BEAM ATTENUATING PROPERTIES OF SUPERFLAB, PLAY‐DOH, AND WET GAUZE, COMPARED TO PLASTIC WATER

Bolus material is used commonly with electron treatments. The purpose of this study was to compare the electron beam attenuating properties of SuperFlab, Play-Doh, and wet gauze to that of plastic water, and evaluate their characteristics as bolus materials for electron beam therapy. Electron beams of 5, 6, 7, 8, 10, and 12 MeV were used. Dose reduction from a range of bolus thicknesses from 2 mm to a thickness well beyond the thickness required to reach peak ioization was measured for each of the bolus materials to establish independent isodose curves. Measurements performed at the known water Dmax for all bolus materials indicated similar results for SuperFlab and plastic water with less than 3% difference for most energies. Play-Doh resulted in more attenuation or less dose buildup compared with plastic water, especially at lower energies. The difference was as high as 24.7% for the beam energy of 5 MeV for Play-Doh. Evaluation of the dose build up curves for all materials indicated the peak dose build up for wet gauze and Play-Doh occurred at lesser thicknesses compared to plastic water and SuperFlab, particularly at lower energies. If Play-Doh and wet gauze are to be used for electron bolus materials, dose build up curves should be established for the machine being used and the appropriate thickness of bolus material be chosen based on those curves.

Use of samarium Sm 153 lexidronam for the treatment of dogs with primary tumors of the skull: 20 cases (1986-2006)

OBJECTIVE To evaluate samarium Sm 153 lexidronam ((153)Sm-EDTMP) as a treatment option for dogs with bony tumors of the skull. DESIGN Retrospective case series. ANIMALS Dogs with multilobular osteochondrosarcoma (MLO) or osteosarcoma (OSA) of the skull. PROCEDURES Veterinary Medical Teaching Hospital records from the Universities of Missouri and Florida from 1986 to 2006 were searched for dogs with primary skull tumors treated with (153)Sm-EDTMP. RESULTS 25 dogs were initially evaluated, with 5 dogs subsequently excluded because of inadequate follow-up or unrelated death. Seven OSAs and 13 MLOs were diagnosed. Tumors involved the occipital and frontal bones (n = 10), zygomatic arch and maxilla region (6), palate (3), and mandible (1). No clinically important adverse effects related to (153)Sm-EDTMP treatment were documented. Of the 20 dogs evaluated 21 days after injection with (153)Sm-EDTMP, 4 had subjective improvement, 13 had progressive disease, and 3 had insufficient follow-up. On the basis of radiographic findings, metastasis was suspected in 1 dog; 16 dogs had no metastasis evident, and medical records were insufficient for 3 dogs. Survival time, defined as the (153)Sm-EDTMP injection date to the date of death, ranged from 3 to 1,314 days (median, 144 days). CONCLUSIONS AND CLINICAL RELEVANCE The subjective improvement in 4 patients and lack of clinical evidence of adverse effects suggested that (153)Sm-EDTMP injection may be an option for the treatment of dogs with MLO or OSA of the skull when other treatments have failed or surgery is not possible.