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

Figures & data

Table 1 Dog weights, three-dimensional tumor volume measurements, percent volume change, and total activity injected into each prostate tumor

Dog	BED group (Gy)	Weight (kg)	Pretreatment tumor volume (cm^3)	Posttreatment tumor volume (cm^3)	Volume decrease (%)	Activity injected (mCi)
1	50	22.4	10.81	7.52	30	4.8
2	50	11	20.06	20.29	−1	3.0
3	105	29.7	50.94	Death prior to week 4	N/A	6.2
4	105	18.8	27.81	31.36	−12	4.5
5	105	33.7	34.06	34.1	−0.1	5.8
6	105	39.6	69.4	71.71	−3	13.8
7	105	21.6	27.44	12.3	55	9.1
8	105	6.6	20.47	19.85	3	6.4
9	105	37	53.65	67.57	−26	8.8

Abbreviation: BED, biologically equivalent dose.

Figure 1 Pre- and 4-week postinjection CT images of one of the dogs with prostatic carcinoma treated with GA-¹⁹⁸AuNP that showed 50% tumor volume reduction.

Notes: (A) CT image of prostate carcinoma of the dog prior to treatment; (B) posttreatment CT image of same dog’s prostate tumor after 4 weeks. These images were chosen to represent the cross-section of the prostate at the same level; respiration, changes in bowel position, size and position of the urinary bladder, and the angle at which the pelvis is positioned affect the position of the prostate within the pelvic cavity between the two imaging studies. Scale bars representing 1 cm per division on these images are at the right hand side of the image. Prostatic volume was calculated in two different ways: the standard geometric formula for calculating the volume of an ellipsoid; and the length × width × height measurements times pi divided by 6 method commonly used in oncology. Measurements were also obtained from a three-dimensional computerized system which calculates the volume of the prostate based on the cross-sectional area and voxel thickness for each section of the prostate.

Abbreviations: CT, computed tomography; GA-¹⁹⁸AuNP, gum arabic-coated radioactive gold nanoparticles.

Table 2 Complete blood count and serum biochemical panel results in six dogs

Parameter	Pretreatment	Week 1	Week 2	Week 3	Week 4
Total white blood cells/μL	10,228 (6,370–16,400)	9,173 (6,240–11,210)	8,295 (6,080–9,780)	8,456 (5,400–17,000)	8,578 (5,900–10,740)
Total red blood cells ×10^6/μL	6.18 (5.6–6.96)	6.55 (5.35–7.15)	6.36 (4.84–7.08)	6.32 (5.34–7.18)	6.33 (5.61–6.91)
Neutrophils/μL	8,284 (4,008–13,776)	6,468 (3,240–9,190)	7,077 (4,090–12,920)	4,951 (4,077–12,920)	6,365 (4,250–7,980)
Platelets ×10^3/μL	361 (217–488)	478 (275–571)	421 (266–531)	425 (338–548)	334 (131–534)
Alkaline phosphatase U/L	150 (39–433)	168 (28–454)	121 (25–311)	88 (32–293)	123 (26–265)
Alanine aminotransferase U/L	32 (17–49)	31 (16–48)	34 (17–73)	39 (10–71)	35 (23–60)
Blood urea nitrogen mg/dL	20 (14–33)	18 (13–29)	23 (10–29)	22 (13–36)	20 (16–29)
Creatinine mg/dL	0.9 (0.6–1)	0.95 (0.8–1.4)	1.02 (0.6–1.7)	1.03 (0.6–1.6)	0.96 (0.6–1.4)

Note: Data are represented as the mean and range.

Figure 2 Scintigraphic images recorded within 30 minutes postinjection of GA-¹⁹⁸AuNP in seven dogs.

Notes: (A–G) Dogs three to nine, respectively. These images reveal presence of radioactive gold nanoparticles within the prostate postinjection as indicated by the blue arrows; the multiple injection points within the prostate tumor are clearly seen in one of the dogs (C). Leakage of small amounts of radioactive gold nanoparticles into bladder, urethra, and extra prostate region following injection in six of seven dogs is noted by the yellow, red, and white arrows, respectively.

Abbreviation: GA-¹⁹⁸AuNP, gum arabic-coated radioactive gold nanoparticles.