Low-energy emission radioimmunotherapy with doses of up to 350 mCi/m2 of 125I-mAb A33 did not cause bowel or bone marrow toxicity. The modest antitumor activity in these heavily pretreated patients is encouraging because of lack of toxicity at the doses studied. The long radioactivity retention in tumors suggests that isotopes with a long half-life may have a therapeutic advantage, based on calculated dose delivery to tumor versus normal tissue. Due to the low bone marrow dose, further 125I trials with humanized mAb A33 are warranted, and controlled studies must be conducted to evaluate the combination of radioimmunotherapy and chemotherapy.

An intraoperative beta probe was designed, built, and tested for detection of radio-labeled malignant tissues that has the advantage of being selectively sensitive to beta while insensitive to gamma radiation. Since beta radiation (electrons or positrons) has a short range in tissue, this probe is ideal for detecting tracers in tumors at the surface of the surgical field. This probe contains a plastic scintillation detector sensitive to beta rays and to a lesser degree some background gamma rays. A second detector counts spurious gamma rays and allows for their subtraction from the activity measured by the first detector. Sensitivity of the dual probe for I-131 and F-18 was measured to be 108 counts/s/kBq (4000 counts/s/microCi). The dual-detector probe faithfully measured the 10:1 "tumor" to background ratio of radioactivity concentrations in a simulated environment of a tumor in the presence of intense background 511 keV photons. In another phantom experiment, simulating abdominal tumor deposits with various realistic I-131 radioactive concentrations, the probe was able to accurately identify tumors of approximately 50 mg with a tumor/normal radioactivity concentration of 3/1 in 10 s.

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The PET-Probe identified all lesions demonstrated by PET scanning and, in selected cases, was useful in localizing FDG-avid disease not seen with conventional PET scanning.

This study is the first to demonstrate the utility of beta probes for the intraoperative detection of radiolabeled antibodies targeting cancer. Importantly, the recorded beta count rates from the beta probe correlate with the count rates from the high-energy gamma probe. Furthermore, the beta probe may offer superior specificity for real-time localization of small tumor deposits, compared to gamma probes. The intraoperative portable PET probe may prove a valuable bridge to combining tumor biology and PET technology to guide surgical therapy.

Isotopes commonly used for PET imaging and quantification have a straightforward decay scheme involving "pure" positron (beta +) emission, i.e., 95%-100% beta + abundance, with no additional gamma rays. 66Ga (Emax = 4.2 MeV, T1/2 = 9.5 h) is a member of a category of isotopes with a lower abundance of beta +'s (57%) and a more complicated spectrum involving combinations of gamma rays that are emitted in cascade. These additional gamma rays tend to cause a higher singles rate, resulting in more random coincidence events. The most abundant positron (51.5%) in the spectrum has one of the highest energies considered for PET imaging. For the purpose of monoclonal antibody dosimetry using 66Ga, it is important to verify the quantification in phantoms prior to initiating human studies. A series of quantitative phantom measurements were performed on the PC4600, a head-optimized BGO based scanner with multiple detector rings. Count rate linearity was verified over concentrations ranging from 4.0 kBq/cc to 37 kBq/cc (0.11-1.0 microCi/cc); resolution averaged 16 mm full width half-maximum in the x and y directions in both the direct and cross planes. Axial resolution was 14 mm. The range of the energetic positrons (up to 4.153 MeV, range 7.6 mm in tissue) was verified as a primary source of resolution degradation. Within the limits outlined above, 66Ga is a suitable isotope for use as 66Ga citrate or with monoclonal antibodies in the detection and staging of tumors and other lesions. In addition, the energetic positrons have possible therapeutic applications when used as a monoclonal antibody label.

Abstract. Nuclear medicine imaging modalities assist commonly in surgical guidance given their functional nature. However, when used in the operating room they present limitations. Pre-operative tomographic 3D imaging can only serve as a vague guidance intra-operatively, due to movement, deformation and changes in anatomy since the time of imaging, while standard intra-operative nuclear measurements are limited to 1D or (in some cases) 2D images with no depth information. To resolve this problem we propose the synchronized acquisition of position, orientation and readings of gamma probes intra-operatively to reconstruct a 3D activity volume. In contrast to conventional emission tomography, here, in a first proof-of-concept, the reconstruction succeeds without requiring symmetry in the positions and angles of acquisition, which allows greater flexibility. We present our results in phantom experiments for sentinel node lymph node localization. The results indicate that 3D intra-operative nuclear images can be generated in such a setup up to an accuracy equivalent to conventional SPECT systems. This technology has the potential to advance standard procedures towards intra-operative 3D nuclear imaging and offers a novel approach for robust and precise localization of functional information to facilitate less invasive, image-guided surgery.

We present a method to assess quantitatively the immunological characteristics of tumours using radiolabelled monoclonal antibody and positron emission tomography (PET) to improve dosimetry for radioimmunotherapy. This method is illustrated with a glioma patient who was injected with 96.2 MBq of iodine-124 labelled 3F8, a murine antibody (IgG3) specific against the ganglioside GD2. Serial PET scans and plasma samples were taken over 11 days. A three-compartment model was used to estimate the plasma to tumour transfer constant (K1), the tumour to plasma transfer constant k2, the association and dissociation constants (k3, k4) of antibody binding, and the binding potential. Tumour radioactivity peaked at 18 h at 0.0045% ID/g. The kinetic parameters were estimated to be: K1 = 0.048 ml h-1 g-1, k2 = 0.16 h-1, k3 = 0.03 h-1, k4 = 0.015 h-1 and BP = 2.25. Based on these kinetic parameters, the amount of tumour-bound radiolabelled monoclonal antibody was calculated. This method permits estimates of both macrodosimetry and microdosimetry at the cellular level based on in vivo non-invasive measurement.