Imaging of therapy-induced apoptosis using (99m)Tc-HYNIC-annexin V in thymoma tumor-bearing mice.

The primary focus of this study was to assess the potential of (99m)Tc-HYNIC-Annexin V for in vivo imaging of apoptosis after systemic chemotherapy and "more localized" radiotherapy in nude mice bearing thymoma tumors and correlating it with TUNEL staining. (99m)Tc-HYNIC-Annexin V was administered intravenously to tumor-bearing mice (n = 25) before and after therapy. Mice were then imaged at 4 hours postinjection, and the animals were subsequently sacrificed. Tumor uptake increased significantly in response to treatment [chemotherapy (n = 8): 1.80 +/- 0.52 %ID/g, p < 0.009; radiotherapy (n = 7): 0.81 +/- 0.07 %ID/g, p < 0.02], compared to the control group (n = 10) (0.57 +/- 0.05 %ID/g). Tumor-to-muscle (T:M) and tumor-to-blood (T:B) ratios were significantly higher in both chemotherapy-treated (p < 0.02 and p < 0.01) and radiotherapy-treated cohorts (p < 0.05 and p < 0.03), compared to the control cohorts at 4 hours postinjection of (99m)Tc-Annxin V. In the post-therapy cohorts, the immunohistochemistry studies indicated a statistically significant correlation between tumor uptake of (99m)Tc-HYNIC-Annexin V and the extent of apoptosis detected by TUNEL-positive staining (r(2) = 0.41). The physiologic localization of the agent was found mainly in the kidneys (34%), liver (11%), and urine (22%). The results suggest that (99m)Tc-HYNIC-Annexin V may be an ideal agent for imaging apoptosis in response to treatment in a thymoma tumor bearing mouse model.

Is (99m)Tc-labelled pamidronate a better agent than (99m)Tc-medronate for bone imaging?

OBJECTIVE: To evaluate the potential of (99m)Tc-pamidronate ((99m)Tc-APD) against (99m)Tc-medronate ((99m)Tc-MDP) as a new bone-seeking agent using intact bone and fractured femur in a rat model. METHODS: (99m)Tc-APD was prepared by the stannous reduction method. Scintigraphic images were obtained at 2 h and 24 h after intravenous injection of (99m)Tc-APD or (99m)Tc-MDP in rats, then they were culled to estimate activities in various organs. Bone uptake (as percent injected dose/gram weight) was estimated in an intact femur and in 1 week post-fracture model. The urinary excretion dose (as percent injected dose) was also estimated. RESULTS: The bone uptake of (99m)Tc-APD was significantly higher (P<0.05) than (99m)Tc-MDP at 2 h and 24 h post-injection studies. (99m)Tc-APD uptake was further increased (P<0.05) in the fracture model than the intact femur. (99m)Tc-APD uptake in the soft tissues including liver and the kidneys was lower than (99m)Tc-MDP. Renal excretion was faster and the ratios of bone to blood and bone to soft tissues were higher with APD than MDP. APD dose was selected at 1% of MDP, to obviate therapeutic effect, as the former compound is 100 times more potent than MDP. CONCLUSIONS: Our results suggest that (99m)Tc-APD uptake by intact bone and fractured bone was significantly higher than (99m)Tc-MDP. The renal clearance of (99m)Tc-APD was faster and soft tissue uptake was lower than (99m)Tc-MDP. These results suggest that APD has the potential to become an excellent bone-imaging agent.

Evaluation of biodistribution by local versus systemic administration of 99mTc-labeled pamidronate.

BACKGROUND: There is an emerging interest in utilizing local and systemic administration of bisphosphonates in orthopedics. The primary objective of this study was to use (99m)Tc-pamidronate ((99m)Tc-PAM) as a tool and compare bone and tissue uptake by local versus systemic administration. METHODS: (99m)Tc-PAM was administered intravenously (i.v.), subcutaneously (s.c.) and by direct application (d.a.) on a surgically exposed and fractured femur (d.a.#f). The animals were imaged at 2 h and 24 h after administration and then killed. Organs were harvested, and their radioactivity was estimated. Specific uptake in the right femur was compared between groups, as was systemic exposure to (99m)Tc PAM. RESULTS: Bone uptake of (99m)Tc-PAM in the i.v. and s.c. groups was 2.2 +/- 0.15 and 0.65 +/- 0.07% ID/g, respectively, at the 2 h time point. Uptake by surgically exposed right femur (d.a) was 5.15 +/- 0.26% ID/g, 134% higher than the femoral uptake by the i.v. method (P < 0.05). In the presence of exposed bone when the femur was fractured (d.a.#f), the uptake was 7.89 +/- 0.46% ID/g, a further 50% increase (P < 0.05). The uptake of (99m)Tc-PAM increased after 24 h of application to 2.4 +/- 0.15, 1.53 +/- 0.09, 7.94 +/- 0.99, and 13.2 +/- 0.80% ID/g) for i.v., s.c., d.a., and d.a.#f methods, respectively. The increases in uptake for the d.a. methods were significantly higher than for the local methods at the 24-h time point (P < 0.05). Although renal uptake was comparable with the i.v. and s.c. methods (0.22 +/- 0.03 and 0.22 +/- 0.04% ID/g), it was significantly lower with the d.a. methods (0.05 +/- 0.07 and 0.16 +/- 0.07% ID/g) (P < 0.05). The corresponding urinary excretion was 55%, 45%, 36%, and 35% of the injected dose at 24 h. CONCLUSIONS: The results indicate that the bone uptake of (99m)Tc-PAM was significantly higher (P = 0.001) and the kidney uptake significantly lower (P = 0.004) with the d.a. methods than with the i.v. or s.c. method. The findings indicate the need for further study into the potential of local administration of bisphosphonates in the presence of orthopedic indications.

Reduced body protein in children with spastic quadriplegic cerebral palsy.

BACKGROUND: No studies have directly measured body protein or validated skinfold-thickness anthropometry and dual-energy X-ray absorptiometry (DXA) to assess body protein in children with spastic quadriplegic cerebral palsy (SQCP). OBJECTIVE: We aimed to measure and evaluate body protein and to determine whether skinfold-thickness anthropometry and DXA can predict body protein in children with SQCP. DESIGN: This was a cross-sectional study of 59 children (22 girls, 37 boys) aged 3.9-19.5 y with SQCP. The children underwent measurements of anthropometric indexes, lean tissue mass by DXA (LTM(DXA)), and total body protein by neutron activation analysis (TBP(NAA)). In addition, TBP was estimated from both skinfold-thickness anthropometry (TBP(SKIN)) and DXA (TBP(DXA)). The agreement of TBP(SKIN) and TBP(DXA) was tested against TBP(NAA) by using Bland and Altman plot analysis. RESULTS: Height and weight SD scores (x +/- SD: -3.1 +/- 1.6 and -4.8 +/- 5.3, respectively) were significantly lower than reference data in the children with SQCP (P < 0.001). TBP(NAA) for age and height was low in the children with SQCP (P < 0.001): 56.1 +/- 17.3% and 81.5 +/- 15.7%, respectively, of the values predicted from control data. TBP(SKIN) and TBP(DXA) were both highly correlated with TBP(NAA): r = 0.90, P < 0.001, and r = 0.91, P < 0.001, respectively. Despite these significant correlations, agreement analyses showed wide variation of up to 33.3% of the mean for both methods. CONCLUSIONS: Body protein in children with SQCP is significantly reduced for age and height. Skinfold anthropometry and DXA show wide variation in estimation of body protein compared with NAA in this group of children.

Role of lymphoscintigraphy for selective sentinel lymphadenectomy.

An essential prerequisite for a successful sentinel node biopsy (SNB) procedure is an accurate map of the pattern of lymphatic drainage from the primary tumor site. The role of lymphoscintigraphy (LS) in SNB is to provide such a map in each patient. This map should indicate not only the location of all sentinel nodes but also the number of SNs at each location. Such mapping can be achieved using 99mTc-labeled small particle radiocolloids, high-resolution collimators with minimal septal penetration, and imaging protocols that detect all SNs in every patient regardless of their location. This is especially important in melanoma patients, since high-quality LS can identify the actual lymphatic collecting vessels as they drain into each SN. The SN is not always found in the nearest node field and is best defined as "any lymph node receiving direct lymphatic drainage from a primary tumor site." Reliable clinical prediction of lymphatic drainage from the skin or breast is not possible. Patterns of lymphatic drainage from the skin are highly variable from patient to patient, even from the same area of the skin. Unexpected lymphatic drainage has been found from the skin of the back to SNs in the triangular intermuscular space and in some patients through the posterior body wall to SNs in the para-aortic, paravertebral, and retroperitoneal areas. Lymphatic drainage from the head and neck frequently involves SNs in multiple node fields, and can occur from the base of the neck up to nodes in the occipital or upper cervical areas or from the scalp down to nodes at the neck base, bypassing many other node groups. Lymphatic drainage from the upper limb can be directly to SNs above the axilla. Drainage to the epitrochlear region from the hand and arm is more common than was previously thought as is drainage to the popliteal region from the foot and leg. Interval nodes, which lie along the course of a lymphatic vessel between a melanoma site and a recognised node field, are not uncommon especially on the trunk. Drainage across the midline of the body is quite frequent on the trunk and in the head and neck region. In breast cancer, although dynamic imaging is usually not possible, an early postmassage image will also often visualize the lymphatic vessels leading to the SN allowing them to be differentiated from any second tier nodes. Small radiocolloid particles are also needed to achieve migration from peritumoral injections sites and LS allows accurately detection of SNs outside the axilla, which occur in about 50% of patients. These nodes may lie in the internal mammary chain, the supraclavicular region, or the interpectoral region. Intramammary interval nodes can also be SNs in some patients. The location of the cancer in the breast is not a reliable guide to lymphatic drainage, since lymph flow often crosses the center line of the breast. Micrometastatic disease can be present in any SN regardless of its location, and for the SNB technique to be accurate all true SNs must be identified and removed in every patient. LS is an important first step in ensuring that this goal is achieved.