Larry A. Spitznagle

Imaging pattern of previously in vitro sensitized and interleukin-2 expanded autologous lymphocytes in human cancer

In vivo patterns of lymphocytes sensitized against autologous tumor (in vitro) were studied in seven patients with metastatic cancer as a potential candidate for an alternative method of radioimmunodetection and adoptive immunocytotherapy. Peripheral blood lymphocytes (PBL) were either activated in Interleukin-2 (IL-2) [lymphokine activated killer (LAK) cells] or sensitized against autologous tumor cells by in vitro co-culture (IVC) and expanded in IL-2 (educated cells); both were then labelled with 111In. Labelled autologous cells (1 x 10(7)-5 x 10(8)) were administered to patients and biodistribution studied by imaging under a gamma camera at various time intervals. In 4/7 cases, imaging with the educated cells showed concentrations of radioactivity at sites that correlated positively with clinically detectable metastatic tumor. By contrast, only one instance of positive uptake was seen with the LAK cells. Other than slight fever in three cases, infusions of labelled PBL were well tolerated. Educated lymphocytes were cytotoxic against autologous tumor cells and the cytotoxic reactivities of the educated cells were maintained in continuous culture in IL-2 for 4-6 weeks. Evidence of accumulation of radiolabelled educated autologous cells at a significantly higher frequency than that of the LAK cells suggests that in vitro expanded educated PBL might be better candidates for radioimmunodetection of human cancer, and continuous cultures of such educated autologous PBL might be sources for repeated administration of these effector cells.

Synthesis of fluorine-18 labeled 21-fluoroprogesterone

21-Fluoroprogesterone has been synthesized by the nucleophilic displacement of the mesyl group of the 21-hydroxypregn-4-ene-3,20-dione 21-methanesulfonate by fluoride ion, as formed from the solvolysis of potassium fluoride in acetonitrile, using 18-Crown-6 as the catalyst. In a similar manner, the synthesis of 21-fluoroprogesterone labeled with fluorine-18 has been accomplished, producing approximately 800 muCi of product from 6 mCi of K18F in one hour. This demonstrates that 18F labeled molecules of potential values as readiopharmaceuticals can be prepared rapidly in sufficient yield to allow animal investigation.

Breast milk content of 131I in a hypothyroid patient.

An oral dose of 185 MBq of 131I (sodium iodide) was administered to a lactating mother for whole body scanning. Breast milk was collected at several points in time, and assayed for radioactivity. The radioiodine concentration in the milk was found to be 4 MBq/dL at 6 h (about 2% of the dose). The radioactivity in breast milk decreased with a biological half-life of about 15 h in this hypothyroid patient. Following ingestion of radioiodide (such as [131I]sodium iodide), the appearance of radiolabel in breast secretion has been well documented. However, data do not appear in the literature on this process in the grossly hypothyroid state. We, therefore, are reporting our experience with such a situation.

Quality control studies of 99mTc-labeled radiopharmaceuticals by high-performance liquid chromatography

Abstract Efficacy of HPLC in the quality control of commonly-used 99 m Tc-labeled radiopharmaceuticals has been evaluated using different columns. μ-Bondagel and μ-Bondapak columns were found to be suitable for the separation of 99 m TcO 4 − from 99 m Tc-labeled HSA and HIDA, respectively. Both of these columns offered marginal utility for DTPA, MDP and PPi.

The Use of a Crown Ether to Synthesize a Fluorine-18 Labeled Steroid

Previous work in this laboratory has shown that 18F-fluoride can be incorporated into useful radiopharmaceuticals. The reaction of 21-hydroxy-4-pregnene-3, 20-dione-21-methanesulfonate with K18F in the presence of 18-Crown-6 was studied. As the relative molar amount of crown ether was increased up to eight times the amount of precursor steroid, the radiochemical yield of 18F-labeled steroid increased. However, the radiochemical yield fell off with larger amounts of crown ether. Using the optimum conditions, 21-18F-fluoroprogesterone was prepared with a radiochemical yield of 23%. Thus 125 µCi of labeled steroid were obtained when 1.0 mCi of K18F was allowed to react for 2 h. The specific activity of the labeled steroid was calculated to be 20 Ci/mol.

Recovery of bone marrow phagocytic activity after chemotherapy for neuroblastoma

An 11 year old girl, with biopsy proven neuroblastoma cells in the bone marrow, had lack of uptake of 99mTc-sulfur colloid in marrow of the pelvic area. Her chemotherapy was changed. A repeat image 25 days later then showed accumulation of radiocolloid in the pelvic region.

Comparison of biodistribution of 3H,32P and 99mTc labeled Gpp(NH)p in tumor bearing hamsters

Biodistribution and tumor uptake studies were carried out with intravenously injected tracer doses of Gpp(NH)p labeled with 3H, 32P or 99mTc . Syrian golden hamsters with cheek pouch carcinomas, induced by repeated topical applications of DMBA, were used as a tumor model. The biodistributions of these three radionuclides were different, indicating significant molecular cleavage of this nucleotide analog. It was also apparent that this compound labeled with 99mTc may not be useful for tumor imaging due to low tumor-to-blood specific activity ratio. The cheek pouch carcinoma tumor model may be valuable for the evaluation of tumor localizing radiopharmaceuticals.